Dandy–Walker malformation (DWM), also known as Dandy–Walker syndrome (DWS), is a rare congenital brain malformation in which the part joining the two
hemispheres of the
cerebellum
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
(the
cerebellar vermis
The cerebellar vermis (from Latin ''vermis,'' "worm") is located in the medial, cortico-nuclear zone of the cerebellum, which is in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior ...
) does not fully form, and the
fourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ve ...
and space behind the cerebellum (the
posterior fossa) are enlarged with
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
. Most of those affected develop
hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
within the first year of life,
which can present as increasing head size, vomiting, excessive sleepiness, irritability,
downward deviation of the eyes and
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
.
Other, less common symptoms are generally associated with comorbid
genetic conditions
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
and can include
congenital heart defects
A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
, eye abnormalities, intellectual disability, congenital tumours, other brain defects such as
agenesis of the corpus callosum
Agenesis of the corpus callosum (ACC) is a rare birth defect in which there is a complete or partial absence of the corpus callosum. It occurs when the development of the corpus callosum, the band of white matter connecting the two hemispheres ...
, skeletal abnormalities, an occipital
encephalocele
Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal develop ...
or underdeveloped genitalia or kidneys.
It is sometimes discovered in adolescents or adults due to mental health problems.
DWM is usually caused by a
ciliopathic
A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while ...
or
chromosomal
A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...
genetic condition, though the causative condition is only identified in around half of those diagnosed before birth
and a third of those diagnosed after birth.
The mechanism involves impaired
cell migration
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular dire ...
and
division
Division or divider may refer to:
Mathematics
*Division (mathematics), the inverse of multiplication
*Division algorithm, a method for computing the result of mathematical division
Military
*Division (military), a formation typically consisting ...
affecting the long period of development of the cerebellar vermis.
The mechanism by which hydrocephalus occurs in DWM is not yet fully understood.
The condition is diagnosed by
MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
or, less commonly,
prenatal ultrasound
Obstetric ultrasonography, or prenatal ultrasound, is the use of medical ultrasonography in pregnancy, in which sound waves are used to create real-time visual images of the developing embryo or fetus in the uterus (womb). The procedure is a stan ...
.
There are other malformations that can strongly resemble DWM, and disagreement exists around the criteria and classifications used for the malformation.
Treatment for most involves the implantation of a
cerebral shunt
A cerebral shunt is a device permanently implanted inside the head and body to drain excess fluid away from the brain. They are commonly used to treat hydrocephalus, the swelling of the brain due to excess buildup of cerebrospinal fluid (CSF). If ...
in infancy. This is usually inserted in the posterior fossa, but a shunt in the
lateral ventricles
The lateral ventricles are the two largest ventricles of the brain and contain cerebrospinal fluid (CSF). Each cerebral hemisphere contains a lateral ventricle, known as the left or right ventricle, respectively.
Each lateral ventricle resemble ...
may be used instead or in conjunction.
Endoscopic third ventriculostomy
Endoscopic third ventriculostomy (ETV) is a surgical procedure for treatment of hydrocephalus in which an opening is created in the floor of the third ventricle using an endoscope placed within the ventricular system through a burr hole. This allo ...
(ETV) is a less invasive option for patients older than 1 year. Posterior fossa shunts are most effective (80% of the time) but carry the highest risk of complications, while ETV is least effective but has the least risk of complications.
The mortality rate is roughly 15%, mostly due to complications from hydrocephalus or its treatment, which can include
subdural haematomas or infection.
The prognosis after successful hydrocephalus treatment is usually good but depends on any associated condition and its symptoms.
Those without hydrocephalus are treated based on any associated symptoms or condition.
The prevalence of DWM is estimated at between 1 in 25,000 to 1 in 50,000.
DWM is the cause of around 4.3% of cases of congenital hydrocephalus
and 2.5% of all cases of hydrocephalus.
At least 21% of those with DWM have a sibling with the malformation, and at least 16% have a parent with the malformation.
The malformation was first described by English surgeon
John Bland-Sutton
Sir John Bland-Sutton, 1st Baronet (21 April 1855 – 20 December 1936), was a British surgeon.
Biography
He was the son of Enfield Highway farmer Charles William Sutton and was educated at the local school. From there, he entered a private an ...
in 1887,
though it was named by German psychiatrist in 1954
after American neurosurgeons
Walter Dandy
Walter Edward Dandy (April 6, 1886 – April 19, 1946) was an American neurosurgeon and scientist. He is considered one of the founding fathers of neurosurgery, along with Victor Horsley (1857–1916) and Harvey Cushing (1869–1939). Dandy is cr ...
and
Arthur Earl Walker, who described it in 1914 and 1942, respectively.
Signs and symptoms
Hydrocephalus
The most frequent and prominent symptoms of DWM are those associated with
hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
in the postnatal period. Hydrocephalus occurs in an estimated 80% of patients with classic DWM. This usually presents within the first year of life (85% of the time), most often within the first 3 months.
Signs of hydrocephalus in infants include increasing head size, vomiting, excessive sleepiness, irritability, downward deviation of the eyes (known as "
sunsetting eyes") and
seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
.
In contrast to classic DWM, only around 30% of those with Dandy–Walker variant (DWV), in which the
posterior fossa is not enlarged, have hydrocephalus.
Neurological
Despite the hypoplastic cerebellar vermis, just over half of individuals with DWM (between 27% and 84%) do not appear to have significant intellectual disability or developmental delay.
However, many of the genetic conditions associated with DWM can present with developmental delay and other brain anomalies.
Agenesis of the corpus callosum
Agenesis of the corpus callosum (ACC) is a rare birth defect in which there is a complete or partial absence of the corpus callosum. It occurs when the development of the corpus callosum, the band of white matter connecting the two hemispheres ...
has been found in between 5% and 17% of those with DWM.
This does not seem to result in intellectual disability on its own, however.
Other brain abnormalities known to be sometimes associated with DWM include
grey matter heterotopia
MRI of a child experiencing seizures. There are small foci of grey matter Heterotopia (medicine)">heterotopia in the corpus callosum, deep to the Cortical dysplasia, dysplastic cortex. (double arrows)
Gray matter heterotopias are neurological d ...
,
pachygyria
Pachygyria (from the Greek "pachy" meaning "thick" or "fat" gyri) is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, ...
(fewer ridges in the brain),
lissencephaly
Lissencephaly (, meaning "smooth brain") is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in ...
(shallower ridges),
polymicrogyria
Polymicrogyria (PMG) is a condition that affects the development of the human brain by multiple small gyri ( microgyri) creating excessive folding of the brain leading to an abnormally thick cortex. This abnormality can affect either one region of ...
,
holoprosencephaly
Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo) fails to develop into two hemispheres, typically occurring between the 18th and 28th day of gestation. Normally, the forebrain is formed and t ...
and
schizencephaly
Schizencephaly () is a rare birth defect characterized by abnormal clefts lined with grey matter that form the ependyma of the cerebral ventricles to the pia mater. These clefts can occur bilaterally or unilaterally. Common clinical features of ...
.
Individuals with these features tend to have developmental delay or seizures. Those without any other central nervous system abnormalities tend to have normal or close-to-normal intellectual development.
A 2003 review found that moderate-to-severe intellectual disability and non-DWM brain abnormalities were only present in those with the most severe cerebellar vermis malformations (less than two
fissures
A fissure is a long, narrow crack opening along the surface of Earth. The term is derived from the Latin word , which means 'cleft' or 'crack'. Fissures emerge in Earth's crust, on ice sheets and glaciers, and on volcanoes.
Ground fissure
A ...
/three lobules in the vermis), and these comprised 16% of their sample. Hydrocephalus also affected all of these patients.
In Dandy–Walker variant (DWV) and mega cisterna magna specifically, which are less severe malformations, there appears to be an increased rate of
psychotic spectrum disorders such as
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
,
bipolar disorder
Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
,
mania
Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wit ...
or
catatonia
Catatonia is a complex neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal. The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during ...
.
Associated anomalies
A 2017 review found the following associations in patients with DWS (usually from an associated genetic condition or abnormality):
* 27% of patients had a
congenital heart defect
A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
. These included
patent ductus arteriosus
''Patent ductus arteriosus'' (PDA) is a medical condition in which the ''ductus arteriosus'' fails to close after birth: this allows a portion of oxygenated blood from the left heart to flow back to the lungs by flowing from the aorta, which has ...
,
coarctation of the aorta
Coarctation of the aorta (CoA or CoAo), also called aortic narrowing, is a congenital condition whereby the aorta is narrow, usually in the area where the ductus arteriosus (ligamentum arteriosum after regression) inserts. The word ''coarctation' ...
,
ventricular septal defect
A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart. The extent of the opening may vary from pin size to complete absence of the ventricular septum, creating one ...
and
atrial septal defect
Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...
. In 2.7% of patients,
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
was reported.
* 24% of patients had at least one ocular abnormality. These included
cataracts
A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...
, small eyes (
microphthalmia
Microphthalmia (Greek: grc, μικρός, mikros, small, label=none, grc, ὀφθαλμός, ophthalmos, eye, label=none, also referred as microphthalmos, is a developmental disorder of the eye in which one (unilateral microphthalmia) or both ( ...
),
chorioretinal
The choroid, also known as the choroidea or choroid coat, is a part of the uvea, the vascular layer of the eye, and contains connective tissues, and lies between the retina and the sclera. The human choroid is thickest at the far extreme rear ...
dysplasia/atrophy,
optic nerve
In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...
dysplasia/atrophy, a small
cornea
The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...
(microcornea) or corneal opacity (leukoma), short-sightedness (
myopia
Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...
) and
coloboma
A coloboma (from the Greek , meaning defect) is a hole in one of the structures of the eye, such as the iris, retina, choroid, or optic disc. The hole is present from birth and can be caused when a gap called the choroid fissure, which is pres ...
(a hole in an eye structure).
* 16% of patients were diagnosed with a mental or behavioural disorder, with 6.4% also having a learning disability. 5.3% had either
bipolar disorder
Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
or a
psychotic spectrum disorder
A spectrum disorder is a mental disorder that includes a range of linked conditions, sometimes also extending to include singular symptoms and traits. The different elements of a spectrum either have a similar appearance or are thought to be cause ...
, and 2.1% had
ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
. Slightly more of these were found in Dandy–Walker variant (DWV) than in classic DWM, despite DWV being less common, at only around 20% of DWS diagnoses.
* Around 12% of patients had cancers or tumours arising from congenital genetic abnormalities. The most common were
neurocutaneous melanosis
Neurocutaneous melanosis is a congenital disorder characterized by the presence of congenital melanocytic nevi on the skin and melanocytic tumors in the leptomeninges of the central nervous system. These lesions may occur in the amygdala, cerebe ...
(5.9%),
hemangiomas
A hemangioma or haemangioma is a usually benign vascular tumor derived from blood vessel cell types. The most common form, seen in infants, is an infantile hemangioma, known colloquially as a "strawberry mark", most commonly presenting on the ski ...
(4.8%, including those with
PHACE syndrome) and
Wilms' tumour
Wilms' tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children, rarely in adults.; and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German surge ...
(4.4%). 3.2% of patients had
congenital melanocytic nevi
The congenital melanocytic nevus is a type of melanocytic nevus (or mole) found in infants at birth. This type of birthmark occurs in an estimated 1% of infants worldwide; it is located in the area of the head and neck 15% of the time.
Signs an ...
, and 2.1% had tongue
hamartoma
A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended fr ...
. The melanocytic tumours in these cases are thought to relate to the same genetic errors in the
development
Development or developing may refer to:
Arts
*Development hell, when a project is stuck in development
*Filmmaking, development phase, including finance and budgeting
*Development (music), the process thematic material is reshaped
*Photographi ...
of the embryonic
neural tube
In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural fold become elevated, a ...
that lead to the DWM, since the subsequent embryonic
neural crest
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...
gives rise to
melanocytes
Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),
the inner ear,
vaginal epithelium, meninges,
bones,
and heart.
...
, among other cells.
* 10% of patients had
endocrine
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
or
metabolic
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
disorders, and 2.7% had excessive hair growth (
hypertrichosis
Hypertrichosis is an abnormal amount of hair growth over the body. The two distinct types of hypertrichosis are generalized hypertrichosis, which occurs over the entire body, and localized hypertrichosis, which is restricted to a certain area. H ...
).
* 9% of patients (almost all with classic DWM) had musculoskeletal abnormalities, which included
scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
or
kyphoscoliosis
Kyphoscoliosis describes an abnormal curvature of the spine in both a coronal and sagittal plane. It is a combination of kyphosis and scoliosis. This musculoskeletal disorder often leads to other issues in patients, such as under-ventilation of ...
and
arthrogryposis Arthrogryposis (AMC) describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning "curving of joints" (', "joint"; ', late Latin form of late Greek ', "hooking").
Children born with one ...
.
* 5.9% of patients had underdeveloped reproductive organs, such as hypoplastic genitalia or undescended testicles (
cryptorchidism
Cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. The word is from Greek () 'hidden' and () 'testicle'. It is the most common birth defect of the male genital tract. About 3% of ...
).
* 5.3% of patients had underdeveloped or polycystic kidneys.
Occipital
encephalocele
Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal develop ...
may occur in DWM.
This has generally been found at rates between 6 and 8%.
It has been suggested to occur to compensate for the increased pressure in the posterior fossa during foetal life.
Syringomyelia
Syringomyelia is a generic term referring to a disorder in which a cyst or cavity forms within the spinal cord. Often, syringomyelia is used as a generic term before an etiology is determined. This cyst, called a syrinx, can expand and elongate ...
occasionally occurs with DWM, though it is not certain how often.
One review reported an occurrence of 4.3% in a sample.
This may be due to herniation of the bottom of the cyst through the
foramen magnum
The foramen magnum ( la, great hole) is a large, oval-shaped opening in the occipital bone of the skull. It is one of the several oval or circular openings (foramina) in the base of the skull. The spinal cord, an extension of the medulla oblon ...
(a similar mechanism to
Chiari malformation
Chiari malformation (CM) is a structural defect in the cerebellum, characterized by a downward displacement of one or both cerebellar tonsils through the foramen magnum (the opening at the base of the skull). CMs can cause headaches, difficu ...
). Alternatively, it may be a result of hydrocephalus, in which it forms as a "fifth ventricle" due to an enlarged
central canal
The central canal (also known as spinal foramen or ependymal canal) is the cerebrospinal fluid-filled space that runs through the spinal cord. The central canal lies below and is connected to the ventricular system of the brain, from which it r ...
.
Rarely,
spina bifida
Spina bifida (Latin for 'split spine'; SB) is a birth defect in which there is incomplete closing of the spine and the membranes around the spinal cord during early development in pregnancy. There are three main types: spina bifida occulta, me ...
has been found with DWM. When it is present, it is usually spina bifida occulta.
Cause
![Fourth_Ventricle_in_the_Human_Cerebellum](https://upload.wikimedia.org/wikipedia/commons/1/19/Fourth_Ventricle_in_the_Human_Cerebellum.svg)
DWM is caused by any disruption to embryonic development that affects the formation of the cerebellar vermis. This is usually a genetic mutation that results in impaired
cell migration
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular dire ...
and
division
Division or divider may refer to:
Mathematics
*Division (mathematics), the inverse of multiplication
*Division algorithm, a method for computing the result of mathematical division
Military
*Division (military), a formation typically consisting ...
. A large number of genetic conditions can result in the anomaly. In a large portion of DWM cases, the condition is identified in the person affected, however in most cases the cause is not identified. At least 21% of those with DWM have a sibling with the malformation, and at least 16% have a parent with the malformation.
Ciliopathic genetic conditions
A genetic condition is identified in around 33% of those diagnosed with DWM after birth.
In a 2017 review, 4.3% were found to have
PHACE syndrome, a condition involving brain, cardiovascular and eye abnormalities, while 2.3% had
Joubert syndrome
Joubert syndrome is a rare autosomal recessive genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination.
Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pig ...
, a condition involving neurological and sometimes eye and kidney abnormalities. Anywhere from 21% to 81% of those with PHACE syndrome have DWM.
Other comorbid genetic conditions that were found included
oculocerebrocutaneous syndrome
Oculocerebrocutaneous syndrome is a condition characterized by orbital cysts, microphthalmia, porencephaly, agenesis of the corpus callosum, and facial skin tags. Presentation
These include
* Skin lesions
** Hypoplastic or aplastic skin defects ...
,
oral-facial-digital syndrome
Orofaciodigital syndrome or oral-facial-digital syndrome is a group of at least 13 related conditions that affect the development of the mouth, facial features, and digits in between 1 in 50,000 to 250,000 newborns with the majority of cases bein ...
,
Coffin–Siris syndrome
Coffin–Siris Syndrome (CSS), first described in 1970 by Dr Coffin and Dr Siris, is a rare genetic disorder that causes developmental delays and absent fifth finger and toe nails.
There had been 31 reported cases by 1991. The number of occurrence ...
,
Meckel–Gruber syndrome
Meckel-Gruber syndrome is a rare, lethal ciliopathic genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (postaxial), hepatic developmental defects, and pulmonary ...
type 7 and
Kallmann syndrome
Kallmann syndrome (KS) is a genetic disorder that prevents a person from starting or fully completing puberty. Kallmann syndrome is a form of a group of conditions termed hypogonadotropic hypogonadism. To distinguish it from other forms of hypog ...
, among many others.
DWM has also been associated with
3C syndrome,
Rubinstein–Taybi syndrome
Rubinstein–Taybi syndrome (RTS) is a rare genetic condition characterized by short stature, moderate to severe learning difficulties, distinctive facial features, and broad thumbs and first toes. Other features of the disorder vary among affect ...
,
Marden–Walker syndrome
Marden–Walker syndrome (MWS) is a rare autosomal recessive congenital disorder. It is characterized by blepharophimosis, microcephaly, micrognathia, multiple joint contractures, arachnodactyly, camptodactyly, kyphoscoliosis and delayed motor de ...
,
Sheldon–Hall syndrome,
Shah–Waardenburg syndrome,
Fryns syndrome,
< Walker–Warburg syndrome
Walker–Warburg syndrome (WWS), also called Warburg syndrome, Chemke syndrome, HARD syndrome (Hydrocephalus, Agyria and Retinal Dysplasia), Pagon syndrome, cerebroocular dysgenesis (COD) or cerebroocular dysplasia-muscular dystrophy syndrome (COD- ...
,
Fukuyama congenital muscular dystrophy
Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal recessive form of muscular dystrophy (weakness and breakdown of muscular tissue) mainly described in Japan but also identified in Turkish and Ashkenazi Jewish patients; fifteen case ...
,
Ellis–van Creveld syndrome,
Fraser syndrome
Fraser syndrome (also known as Meyer-Schwickerath's syndrome, Fraser-François syndrome, or Ullrich-Feichtiger syndrome) is an autosomal recessive congenital disorder, identified by several developmental anomalies. Fraser syndrome is named for t ...
,
Aicardi syndrome
Aicardi syndrome is a rare genetic malformation syndrome characterized by the partial or complete absence of a key structure in the brain called the corpus callosum, the presence of retinal lacunes, and epileptic seizures in the form of infanti ...
,
Cornelia de Lange syndrome
Cornelia de Lange syndrome (CdLS) is a genetic disorder. People with this syndrome experience a range of physical, cognitive, and medical challenges ranging from mild to severe. The syndrome has a widely varied phenotype, meaning people with the sy ...
,
< Klippel–Feil syndrome
Klippel–Feil syndrome (KFS), also known as cervical vertebral fusion syndrome, is a rare congenital condition characterized by the abnormal fusion of any two of the seven bones in the neck (cervical vertebrae). It results in a limited ability ...
and
acrocallosal syndrome
Acrocallosal syndrome (also known as ACLS) is an extremely rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and intellectual disabilities, and other symptoms. The syndrom ...
, among others. Many of these disorders are classified as
ciliopathies, genetic disorders that affect the cellular
primary cilia
The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
, thin cell projections made from
microtubules
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ...
that are believed to be crucial in signalling embryonic
cell division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukar ...
and
migration
Migration, migratory, or migrate may refer to: Human migration
* Human migration, physical movement by humans from one region to another
** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
.
DWM is one of the single largest predictors of a ciliopathic genetic disease.
Other genes that have been linked to DWM include ''
ZIC1
ZIC1 is a member of the ''Zi''nc finger of the ''c''erebellum (ZIC) protein family.
ZIC1 is classified as a ZIC protein due to conservation of the five C2H2 zinc fingers, which enables the protein to interact with DNA and proteins. ZIC1 is found ...
'', ''
ZIC4'', ''
FOXC1
Forkhead box C1, also known as FOXC1, is a protein which in humans is encoded by the ''FOXC1'' gene.
Function
This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding fork head domain. ...
'', ''
FGF17
Fibroblast growth factor 17 is a protein that in humans is encoded by the ''FGF17'' gene.
The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad Mitogen, mitogenic and cell surv ...
'', ''
LAMC1
Laminin subunit gamma-1 is a protein that in humans is encoded by the ''LAMC1'' gene.
Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide var ...
'' and ''
NID1
Nidogen-1 (NID-1), formerly known as entactin, is a protein that in humans is encoded by the ''NID1'' gene. Both nidogen-1 and nidogen-2 are essential components of the basement membrane alongside other components such as type IV collagen, proteog ...
''.
Chromosomal abnormalities
In those who are diagnosed with DWM before birth on
ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
, up to half are found to have a
chromosomal abnormality
A chromosomal abnormality, chromosomal anomaly, chromosomal aberration, chromosomal mutation, or chromosomal disorder, is a missing, extra, or irregular portion of chromosomal DNA. These can occur in the form of numerical abnormalities, where ther ...
,
with the most common being
Edwards syndrome
Edwards syndrome, also known as trisomy 18, is a genetic disorder caused by the presence of a third copy of all or part of chromosome 18. Many parts of the body are affected. Babies are often born small and have heart defects. Other features in ...
(trisomy 18), at roughly 26% of prenatal DWM cases.
6.5% of those diagnosed with DWM after birth also have Edwards syndrome.
Other chromosomal abnormalities that can lead to DWM include
triploidy
Polyploidy is a condition in which the cells of an organism have more than one pair of ( homologous) chromosomes. Most species whose cells have nuclei ( eukaryotes) are diploid, meaning they have two sets of chromosomes, where each set contain ...
,
Patau syndrome
Patau syndrome is a syndrome caused by a chromosome, chromosomal abnormality, in which some or all of the Cell (biology), cells of the body contain Trisomy, extra genetic material from chromosome 13 (human), chromosome 13. The extra genetic mater ...
(trisomy 13),
trisomy 9
Full trisomy 9 is a lethal chromosomal disorder caused by having three copies (trisomy) of chromosome number 9. It can be a viable condition if trisomy affects only part of the cells of the body (mosaicism) or in cases of partial trisomy (triso ...
and partial 3q deletion or duplication.
The 3q24 region contains the ''ZIC1'' and ''ZIC4'' genes, known to be associated with DWM.
External toxins
Warfarin
Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...
use during pregnancy has been known to lead to
systemic defects in the fetus, including ocular dysgenesis,
microcephaly
Microcephaly (from New Latin ''microcephalia'', from Ancient Greek μικρός ''mikrós'' "small" and κεφαλή ''kephalé'' "head") is a medical condition involving a smaller-than-normal head. Microcephaly may be present at birth or it ...
,
agenesis of the corpus callosum
Agenesis of the corpus callosum (ACC) is a rare birth defect in which there is a complete or partial absence of the corpus callosum. It occurs when the development of the corpus callosum, the band of white matter connecting the two hemispheres ...
, skeletal abnormalities and
heart defects
A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
. In 1985, it was also linked to DWM.
Pathophysiology
![Gray708](https://upload.wikimedia.org/wikipedia/commons/b/b9/Gray708.svg)
The
cerebellum
The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cerebel ...
begins forming at the fifth week of embryonic development. It differentiates at the top of the
metencephalon
The metencephalon is the embryonic part of the hindbrain that differentiates into the pons and the cerebellum. It contains a portion of the fourth ventricle and the trigeminal nerve (CN V), abducens nerve (CN VI), facial nerve (CN VII), and a port ...
, while the
pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum.
The pons is also called the pons Varolii ("bridge of Va ...
(in the brainstem) differentiates at the bottom, separated by the
fourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ve ...
. The
cerebellar hemispheres
The cerebellum consists of three parts, a median and two lateral, which are continuous with each other, and are substantially the same in structure. The median portion is constricted, and is called the vermis, from its annulated appearance which ...
form from the
rhombic lips on the forward surface of the fourth ventricle, which expand and roll over to fuse in the midline to form the cerebellar vermis by the 15th week. If this process does not complete, the cerebellar vermis will not form fully. This long period of development of the cerebellar vermis makes it particularly vulnerable to disruptions.
In DWM, the fourth ventricle opens up into and is continuous with almost the entire
posterior fossa subarachnoid space
In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in th ...
.
Pathophysiology of hydrocephalus
The reason why hydrocephalus occurs in DWM is not yet fully understood. The earliest authors had put it down it to blockage or narrowing of the
foramina of Magendie and
Luschka, the two apertures in the fourth ventricle that allow
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
(CSF) to escape into the subarachnoid space of the posterior fossa. However, later studies found that these foramina are usually open in DWM.
Hydrocephalus is also usually (80% of the time) not present at birth in those with DWM.
The impairment to CSF flow may lie beyond the outlets of the fourth ventricle. Theories of abnormal development or
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
of the
arachnoid mater
The arachnoid mater (or simply arachnoid) is one of the three meninges, the protective membranes that cover the brain and spinal cord. It is so named because of its resemblance to a spider web. The arachnoid mater is a derivative of the neural c ...
in the posterior fossa have been put forward.
The arachnoid mater contains
granulations necessary to return CSF from the subarachnoid spaces to the
dural veins and circulation. Excisions of the cyst in DWM have not been able to show whether impaired arachnoid absorption is involved, since the subarachnoid space always takes days to weeks to fill up following excision.
Aqueductal stenosis
Aqueductal stenosis is a narrowing of the aqueduct of Sylvius which blocks the flow of cerebrospinal fluid (CSF) in the ventricular system. Blockage of the aqueduct can lead to hydrocephalus, specifically as a common cause of congenital and/or ob ...
(narrowing of the passage between the third and fourth ventricles) does not seem to be a factor in DWM. It is usually open, and shunts placed in the posterior fossa cyst almost always drain all above ventricles. When it is present, it may be the result of compression from a herniated vermis or cyst or an associated developmental abnormality.
It is known that once hydrocephalus has started, the compression by the posterior fossa cyst against the venous passages in the arachnoid mater is involved in the worsening pathology.
Diagnosis
Dandy–Walker malformation is diagnosed based on the characteristic neuroimaging findings. It can be diagnosed prenatally on
ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
as early as 14 weeks of gestation, although it is usually diagnosed postnatally by
MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
. It is diagnosed within the first year of life 41% of the time, normally due to increasing signs of
hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
,
but 28% of the time it is discovered in adolescence or adulthood due to mental health problems, such as
psychosis
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
or
mood disorder
A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the ''Diagnostic and Stat ...
.
Criteria and classification
The precise diagnostic criteria and classification systems of DWM are not agreed upon, and significant dispute exists as to which terms or criteria should be used.
The core criteria of DWM are hypoplasia of the
cerebellar vermis
The cerebellar vermis (from Latin ''vermis,'' "worm") is located in the medial, cortico-nuclear zone of the cerebellum, which is in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior ...
and an enlarged
fourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ve ...
and
posterior fossa (the space behind the cerebellum), though the specific degree of hypoplasia or cystic enlargement for diagnosis of DWM is not agreed upon.
Additionally, there are several similar conditions which have at various times been grouped with DWM on a continuum by some authors and separated as distinct by others, further complicating diagnosis.
In 1976, Harwood-Nash and Fitz proposed the term Dandy–Walker variant (DWV) for a malformation in which the posterior fossa is not enlarged but the cerebellar vermis is hypoplastic.
In 1989, Barkovich et al. proposed the term Dandy–Walker complex (DWC) to include classic DWM and DWV (under type A) plus a third malformation (under type B) in which the cerebellar vermis remains large enough to sit between the fourth ventricle and the
cisterna magna
The cisterna magna (or cerebellomedullar cistern) is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain. The openings are collectively referred to as the su ...
beneath it, and instead it is mostly the cisterna magna that is enlarged. In this type, the hypoplasia of the cerebellar vermis does not reach past the horizontal midline of the fourth ventricle, and the posterior fossa is also not as large. The authors noted that this form would previously have been classified as simply mega–cisterna magna.
In 1999, Calabró et al. first used the phrase Dandy–Walker continuum when referring to proposals that a condition known as Blake's pouch cyst falls under the umbrella of the Dandy–Walker complex proposed by Barkovich.
Later authors would put these terms and systems under intense scrutiny and state that they added considerable confusion to the diagnosis of DWM.
However, they remain commonly used.
In 2011, Spennato et al. came up with a set of criteria based on Klein et al. (2003) that they considered necessary for diagnosis of DWM:
* The lower portion of the
cerebellar vermis
The cerebellar vermis (from Latin ''vermis,'' "worm") is located in the medial, cortico-nuclear zone of the cerebellum, which is in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior ...
is absent to varying degrees (three quarters, one half or one quarter missing).
* The
posterior fossa (the space behind the cerebellum) is enlarged, and its
cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
flow is continuous with that of the fourth ventricle.
* The rest of the cerebellar vermis is hypoplastic and is pushed upwards and rotated forwards due to the enlarged posterior fossa.
* The
cerebellar hemispheres
The cerebellum consists of three parts, a median and two lateral, which are continuous with each other, and are substantially the same in structure. The median portion is constricted, and is called the vermis, from its annulated appearance which ...
are pushed forwards and to the side by the enlarged posterior fossa.
* The angle at the centre of the cerebellar vermis (representing the location of the
fastigial nucleus
The fastigial nucleus is located in the cerebellum. It is one of the four deep cerebellar nuclei (the others being the nucleus dentatus, nucleus emboliformis and nucleus globosus), and is grey matter embedded in the white matter of the cerebell ...
) is large, giving a flattened appearance to the bottom of the vermis, or the fastigial nucleus is absent entirely.
* The
confluence of sinuses
The confluence of sinuses (Latin: confluens sinuum), torcular Herophili, or torcula is the connecting point of the superior sagittal sinus, straight sinus, and occipital sinus. It is below the internal occipital protuberance of the skull. It drai ...
, part of the drainage system located at the far rear of the
occipital lobe
The occipital lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The name derives from its position at the back of the head, from the Latin ''ob'', "behind", and ''caput'', "head".
The occipital lobe is the vi ...
, is elevated due to the enlarged posterior fossa. (The adjacent
cerebellar tentorium
The cerebellar tentorium or tentorium cerebelli (Latin for "tent of the cerebellum") is an extension of the dura mater that separates the cerebellum from the inferior portion of the occipital lobes.
Structure
The cerebellar tentorium is an arche ...
is also elevated.)
Due to the inconsistency of the presence of hydrocephalus in DWM, Spennato and Klein suggested that it should not be considered a criterion for DWM.
Klein's criteria differed from Spennato's mainly in that it required no apparent cerebellar hemisphere hypoplasia, but it may also have required the vermis to touch the tentorium or an absence of
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
abnormalities.
Methods
DWM can be observed prenatally on
ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
as early as 14 weeks of gestation,
though an
MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
scan is the most useful method for diagnosis. MRI can delineate the shape and extent of the malformation as well as assessing additional areas for malformations such as the cerebellar hemispheres,
cerebral aqueduct
The cerebral aqueduct (aqueductus mesencephali, mesencephalic duct, sylvian aqueduct or aqueduct of Sylvius) is a conduit for cerebrospinal fluid (CSF) that connects the third ventricle to the fourth ventricle of the ventricular system of the brai ...
or
corpus callosum
The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental mam ...
. Cardiac-gated
phase-contrast MRI can observe the flow of cerebrospinal fluid (CSF) during
systole
Systole ( ) is the part of the cardiac cycle during which some chambers of the heart contract after refilling with blood. The term originates, via New Latin, from Ancient Greek (''sustolē''), from (''sustéllein'' 'to contract'; from ''sun ...
and
diastole
Diastole ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are re-filling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventric ...
of the heart. In true DWM, this will find a flow from the cerebral aqueduct to the posterior fossa and no flow between the cisterna magna and the space behind the cervical spinal cord.
CT may also be used if MRI is unavailable, but it provides less detail.
Klein et al. (2003) suggested that a suspected diagnosis based on CT or ultrasound should not be confirmed until an MRI is performed, due to the large number of conditions that can present highly similarly and confound diagnosis.
Differential diagnosis
DWM has a large number of conditions that can present highly similarly on imaging and confound diagnosis.
Blake's pouch cyst
Blake's pouch cyst (BPC), or persistent Blake's pouch, is a condition that arises when Blake's pouch, an invagination in the fourth ventricle that ruptures at around 4 months of gestation to form the
foramen of Magendie (medial aperture), fails to rupture. This can lead to a dilated fourth ventricle and subsequent hydrocephalus of all four ventricles.
In a Blake's pouch cyst, unlike in DWM:
* The cerebellum is not hypoplastic, though it may be compressed by the enlarged posterior fossa (
mass effect
''Mass Effect'' is a military science fiction media franchise created by Casey Hudson, Drew Karpyshyn and Preston Watamaniuk. The franchise depicts a distant future where humanity and several alien civilizations have colonized the known univers ...
).
* The posterior fossa is not enlarged.
* The cerebellar tentorium/confluence of sinuses is not raised.
* Hydrocephalus, when it occurs, involves all four ventricles.
Some authors, however, consider Blake's pouch cyst part of a continuum with DWM (the "Dandy–Walker continuum").
Mega cisterna magna
Mega cisterna magna is a condition in which the
cisterna magna
The cisterna magna (or cerebellomedullar cistern) is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain. The openings are collectively referred to as the su ...
, the
subarachnoid cistern
The subarachnoid cisterns are spaces formed by openings in the subarachnoid space, an anatomic space in the meninges of the brain. The space is situated between the two meninges, the arachnoid mater and the pia mater. These cisterns are filled ...
below the fourth ventricle, is enlarged. It has been proposed to be due to a delayed rupture of Blake's pouch rather than a failed rupture.
In mega cisterna magna, unlike in DWM:
* The cerebellum is not usually hypoplastic.
* The fourth ventricle is of relatively normal shape.
* Hydrocephalus is uncommon.
There is debate as to whether this malformation is distinct from DWM or forms part of the "Dandy–Walker continuum".
Posterior fossa arachnoid cyst
An arachnoid cyst is a collection of cerebrospinal fluid (CSF) in the
arachnoid mater
The arachnoid mater (or simply arachnoid) is one of the three meninges, the protective membranes that cover the brain and spinal cord. It is so named because of its resemblance to a spider web. The arachnoid mater is a derivative of the neural c ...
. 10% of these occur in the posterior fossa.
In a posterior fossa arachnoid cyst, unlike in DWM:
* The cyst is clearly localised in a specific location separate from the fourth ventricle outlets.
* The cerebellum is not hypoplastic, though it may be compressed by the cyst (mass effect).
* The CSF flow in the cyst is not continuous with that of the fourth ventricle.
* Hydrocephalus, if it occurs, is due to the cyst pressing on the cerebellum and compressing the
cerebral aqueduct
The cerebral aqueduct (aqueductus mesencephali, mesencephalic duct, sylvian aqueduct or aqueduct of Sylvius) is a conduit for cerebrospinal fluid (CSF) that connects the third ventricle to the fourth ventricle of the ventricular system of the brai ...
or fourth ventricle outlets.
Treatment
The main immediate goal of treatment is the control of hydrocephalus and the enlarged posterior fossa cyst, as these can lead to increased
intracranial pressure
Intracranial pressure (ICP) is the pressure exerted by fluids such as cerebrospinal fluid (CSF) inside the skull and on the brain tissue. ICP is measured in millimeters of mercury (mmHg) and at rest, is normally 7–15 Millimeter of mercury, mmHg ...
and brain damage. A minority of those affected do not develop hydrocephalus and are treated based on any associated symptoms or condition.
Hydrocephalus/cyst
For hydrocephalus or the posterior fossa cyst,
shunts are the mainstay of treatment. However, those with DWM have a higher rate of shunt-related complications than other patients with hydrocephalus (mainly due to the unconventional anatomy).
One explanation for a failure of a shunt to reduce intracranial pressure in DWM has been that the cyst may herniate into the
foramen magnum
The foramen magnum ( la, great hole) is a large, oval-shaped opening in the occipital bone of the skull. It is one of the several oval or circular openings (foramina) in the base of the skull. The spinal cord, an extension of the medulla oblon ...
and form a scarring adhesion at the cervical junction, preventing it from shrinking again. If this occurs, a suboccipital decompression with duraplasty may be attempted.
In DWM, it is not agreed whether a shunt should be placed in the
fourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ve ...
(a cystoperitoneal shunt, or CP shunt), the
lateral ventricles
The lateral ventricles are the two largest ventricles of the brain and contain cerebrospinal fluid (CSF). Each cerebral hemisphere contains a lateral ventricle, known as the left or right ventricle, respectively.
Each lateral ventricle resemble ...
(a ventriculoperitoneal shunt, or VP shunt) or both, due to conflicting studies on whether the
cerebral aqueduct
The cerebral aqueduct (aqueductus mesencephali, mesencephalic duct, sylvian aqueduct or aqueduct of Sylvius) is a conduit for cerebrospinal fluid (CSF) that connects the third ventricle to the fourth ventricle of the ventricular system of the brai ...
is
affected by the malformation. However, a CP shunt almost always drains both the fourth and lateral ventricles in DWM, and according to strict definitions of the malformation, the aqueduct should be assumed open,
though imaging is important to confirm this.
Many authors therefore recommend the CP shunt as the logical option. However, it is associated with a high rate of complications, including shifting and overdrainage. Overdrainage can lead to
subdural haematomas, a
tethered spinal cord
Tethered cord syndrome (TCS) refers to a group of neurological disorders that relate to malformations of the spinal cord.[cerebral hemispheres
The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres ...]
. Spennato et al. therefore recommend a flow-regulating or anti-syphon valve. On the other hand, VP shunts have a lower rate of complications than CP shunts and are recommended initially by some. However, they are less effective in DWM, and the elevated position of the
tentorium should be considered before installing a VP shunt.
In patients older than 1 year,
endoscopic third ventriculostomy
Endoscopic third ventriculostomy (ETV) is a surgical procedure for treatment of hydrocephalus in which an opening is created in the floor of the third ventricle using an endoscope placed within the ventricular system through a burr hole. This allo ...
(ETV) may be considered as the first-line treatment. This less invasive procedure creates an artificial hole in the
third ventricle
The third ventricle is one of the four connected ventricles of the ventricular system within the mammalian brain. It is a slit-like cavity formed in the diencephalon between the two thalami, in the midline between the right and left lateral v ...
to allow CSF to bypass any obstruction. It cannot be used on those with brain abnormalities such as agenesis of the corpus callosum, due to the risk of CSF escaping to other brain areas. A compressed
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
is not a contraindication, however. ETV has a more modest success rate than shunts, as the hole often closes over. It is more likely to fail in younger patients (below 1 year), and its effects on the developing brain are not yet known.
Cysts posterior to the cerebellum, presenting in children younger than 5 years, have been labeled developmental retrocerebellar cysts under a new classification in relation to the proposed neuroendoscopic management.
Previously,
craniotomy
A craniotomy is a surgical operation in which a bone flap is temporarily removed from the skull to access the brain. Craniotomies are often critical operations, performed on patients who are suffering from brain lesions, such as tumors, blood clots ...
of the posterior fossa and excision of the cystic membrane was used, which was often unsuccessful in preventing cyst reformation and carried a degree of mortality. This may still be reserved for patients with repeated shunt failures/infections.
Other
Treatments for any other symptoms are generally focussed on the specific condition involved and may include supported education, physical therapy or other services. Genetic counselling may be offered to parents for future conceptions.
Prognosis
The prognosis is first and foremost dependent on the early and successful treatment of hydrocephalus, if present. The other significant factor affecting prognosis is the presence of a comorbid genetic condition or brain anomaly.
Mortality rates from DWM are roughly 15%.
In a study of Dandy–Walker variant (DWV), a mortality rate of 12.5% was observed.
The most common cause of death is complications from hydrocephalus or its treatment.
Untreated hydrocephalus can lead to increased intracranial pressure and brain damage. Shunts used to treat DWM have a moderate-to-good success rate, but they have a higher-than-average failure rate, which can result in failure to reduce the intracranial pressure or infection, such as
meningitis
Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
. Complications from overdrainage such as
subdural haematomas are also possible and can lead to mortality.
Shunts in the fourth ventricle (cystoperitoneal shunts, or CP shunts) have a generally high rate of successful cyst and ventricle size reduction, especially in the cyst (at least 80%). With a shunt in the lateral ventricles (ventriculoperitoneal shunt, or VP shunt), studies have generally found a roughly 50% successful cyst size reduction rate, with successful ventricle size reduction roughly two thirds of the time.
Other systemic or genetic conditions are often present with DWM, and each have their own significant effect on prognosis.
Epidemiology
The prevalence of DWM is estimated at between 1 in 25,000 to 1 in 50,000.
DWM is the cause of around 4.3% of cases of congenital hydrocephalus
and 2.5% of all cases of hydrocephalus.
A 2017 review found that most patients (65%) were diagnosed with either "Dandy–Walker malformation" or "Dandy–Walker syndrome", while 20% were diagnosed with "Dandy–Walker variant" and 1.1% with "mega cisterna magna".
History
The malformation was first described in 1887 by English surgeon
John Bland-Sutton
Sir John Bland-Sutton, 1st Baronet (21 April 1855 – 20 December 1936), was a British surgeon.
Biography
He was the son of Enfield Highway farmer Charles William Sutton and was educated at the local school. From there, he entered a private an ...
as hypoplasia of the
cerebellar vermis
The cerebellar vermis (from Latin ''vermis,'' "worm") is located in the medial, cortico-nuclear zone of the cerebellum, which is in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior ...
, an enlarged
posterior fossa and
hydrocephalus
Hydrocephalus is a condition in which an accumulation of cerebrospinal fluid (CSF) occurs within the brain. This typically causes increased intracranial pressure, pressure inside the skull. Older people may have headaches, double vision, poor ...
.
In 1914, American neurosurgeon
Walter Dandy
Walter Edward Dandy (April 6, 1886 – April 19, 1946) was an American neurosurgeon and scientist. He is considered one of the founding fathers of neurosurgery, along with Victor Horsley (1857–1916) and Harvey Cushing (1869–1939). Dandy is cr ...
and American paediatrician
Kenneth Blackfan
Kenneth Blackfan (September 9, 1883 – November 29, 1941) was an American pediatrician. He took particular interest in nutrition and hematology. A childhood blood disorder, Diamond–Blackfan anemia, is partly named after him. Early in his care ...
described the malformation as partial or complete absence of the cerebellar vermis, an enlarged fourth ventricle and hydrocephalus.
In 1942, American physician John K. Taggart and Canadian–American neurosurgeon
Arthur Earl Walker detailed the phenomenon extensively, ascribing the potential cause as underdevelopment of the
foramina of Luschka and
Magendie,
now no longer believed to be significant.
The term Dandy–Walker syndrome (DWS) was introduced by German psychiatrist in 1954; he also used the term ''Dandy–Walker malformation'' once.
In 1976, Harwood-Nash and Fitz proposed the term Dandy–Walker variant (DWV) for a malformation in which the posterior fossa is not enlarged but the cerebellar vermis is hypoplastic.
In 1989, Barkovich et al. proposed the term Dandy–Walker complex (DWC) to include classic DWM and DWV (under type A) plus a third malformation (under type B) in which the cerebellar vermis remains large enough to sit between the fourth ventricle and the
cisterna magna
The cisterna magna (or cerebellomedullar cistern) is one of three principal openings in the subarachnoid space between the arachnoid and pia mater layers of the meninges surrounding the brain. The openings are collectively referred to as the su ...
, and instead it is mostly the cisterna magna that is enlarged (sometimes diagnosed as "mega cisterna magna"). In 1999, Calabró et al. first used the phrase Dandy–Walker continuum when referring to proposals that a condition known as Blake's pouch cyst falls under the umbrella of the Dandy–Walker complex proposed by Barkovich.
These additional terms are mostly discouraged by modern authors due to additional confusion and complexity to the diagnosis of DWM.
References
Further reading
''Metry Phaces article''in the Journal of Pediatrics, July 2001
from Pan Arab Journal of Neurosurgery
External links
{{DEFAULTSORT:Dandy-Walker Syndrome
Congenital disorders of nervous system
Rare syndromes
Syndromes affecting the cerebellum
Syndromes affecting the nervous system