Marden–Walker syndrome (MWS) is a rare

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosom ...

recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

congenital disorder A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities ca ...

. It is characterized by

blepharophimosis Blepharophimosis is a congenital anomaly in which the eyelids are underdeveloped such that they cannot open as far as usual and permanently cover part of the eyes. Both the vertical and horizontal palpebral fissures (eyelid openings) are shortene ...

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 ...

micrognathia Micrognathism is a condition where the jaw is undersized. It is also sometimes called mandibular hypoplasia. It is common in infants, but is usually self-corrected during growth, due to the jaws' increasing in size. It may be a cause of abnorm ...

, multiple

joint A joint or articulation (or articular surface) is the connection made between bones, ossicles, or other hard structures in the body which link an animal's skeletal system into a functional whole.Saladin, Ken. Anatomy & Physiology. 7th ed. McGraw- ...

contractures,

arachnodactyly Arachnodactyly ("spider fingers") is a medical condition that is characterized by fingers and toes that are abnormally long and slender, in comparison to the palm of the hand and arch of the foot. In some cases, the thumbs of an individual with the ...

camptodactyly Camptodactyly is a medical condition that causes one or more fingers or toes to be permanently bent. It involves fixed flexion deformity of the proximal interphalangeal joints. Camptodactyly can be caused by a genetic disorder. In that case, it ...

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 delayed motor development and is often associated with

cystic A cyst is a closed sac, having a distinct envelope and division compared with the nearby tissue. Hence, it is a cluster of cells that have grouped together to form a sac (like the manner in which water molecules group together to form a bubble); ...

dysplastic

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

dextrocardia Dextrocardia (from Latin ''dextro'', meaning "right hand side," and Greek ''kardia'', meaning "heart") is a rare congenital condition in which the apex of the heart is located on the right side of the body, rather than the more typical placement t ...

Dandy–Walker malformation 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 cerebellar vermis) does not fully form, and the fourth ...

and agenesis of corpus callosum.

Signs and symptoms

Most of the signs of MWS are present during the neonatal period. The most common signs at this state are multiple congenital joint contractures, dysmorphic features with mask-like face,

, ptosis,

, cleft or high arched palate, low-set ears,

, chest deformation as pectus,

and absent deep tendon reflexes are frequent minor malformations have also been described and consist of renal anomalies, cardiovascular abnormalities,

hypospadias Hypospadias is a common variation in fetal development of the penis in which the urethra does not open from its usual location in the head of the penis. It is the second-most common birth abnormality of the male reproductive system, affecting abou ...

, omphalomesenteric duct, hypertriphic pyloric stenosis, duodenal bands, hyoplastic right lower lobe of the lung, displacement of the larynx to the right and vertebral abnormalities, cerebral malformations. * 75% of children with MWS have

, small mouth, micrognathia,

kyphosis Kyphosis is an abnormally excessive convex curvature of the spine as it occurs in the thoracic and sacral regions. Abnormal inward concave ''lordotic'' curving of the cervical and lumbar regions of the spine is called lordosis. It can result ...

/ scoliosis, radio ulnar synostose and multiple contractures. * They have severe developmental delay; congenital joint contractures and blepharophimosis should be present in every patient * 2 out of 3 of the following signs should be manifested: post natal growth, mask-like faces, retardation, and decreased muscular mass. * Some may require additional signs such as;

, high arched or cleft palate, low set ears,

. * The symptoms of MWS are normally diagnosed during the newborn period.

Progression

The natural history of MWS is not well known: many patients died in infancy and clinical follow-up has been reported in few surviving adults. However, diagnosis may be more difficult to establish in adults patients, such as:

contractures In pathology, a contracture is a permanent shortening of a muscle or joint. It is usually in response to prolonged hypertonia, hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions ...

growth retardation Delayed milestone, also called developmental delays, is used to describe the condition where a child does not reach one of these stages at the expected age. However, in most cases, a wide variety of ages can be considered normal, and not a cause fo ...

, and

developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech ...

, whereas minor face anomalies are less noticeable as the patient grows older. Throughout the development of the patient from young child to older adult changes the behavior drastically, from kindness to restless and hyperactive to aggressive.

Cause

MWS is a heterogeneous, initially described as a syndrome. But this condition is more on the lines of a

phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

expression of various heterogeneous diseases and belongs to the second group in the classification of

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 ...

. Unknown congenital myopathy has been suspected to underlie MWS due to muscular involvement, but extension of the

neuromuscular A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation ...

systems failed to identify a primary myopathy in patients with MWS. Secondary muscle involvement from a CNS lesion may occur. This could lead to congenital weakness with hypoatonia deep tendon reflex.

Genetics

MWS is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both

carry Carry or carrying may refer to: People *Carry (name) Finance * Carried interest (or carry), the share of profits in an investment fund paid to the fund manager * Carry (investment), a financial term: the carry of an asset is the gain or cost of h ...

one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.

Pathophysiology

Though the pathomechanism of Marden–Walker syndrome is unknown, it may be caused by a genetic defect which manifests as a dysfunctional molecular mechanism in the primary cilia structures of the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

. These organelles are present in many cellular types throughout the

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...

body. The cilia defects adversely affect "numerous critical developmental signaling pathways" essential to cellular development.

Diagnosis

Management

The only treatment for MWS is only symptomatic, with multidisciplinary management

Epidemiology

There have been 30 cases of Marden-Walker Syndrome reported since 1966. The first case of this was in 1966 a female infant was diagnosed with

, joint contractures, arachnodactyly and growth development delay. She ended up dying at 3 months due to pneumonia.

References

External links

* * {{DEFAULTSORT:Marden-Walker syndrome Autosomal recessive disorders Congenital disorders Rare syndromes Syndromes affecting head size Genetic disorders with OMIM but no gene Syndromes affecting the nervous system Syndromes affecting the eye Syndromes affecting the heart Syndromes affecting the kidneys