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 autosome ...

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 ...

congenital disorder A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

. 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 Neo-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 m ...

, micrognathia, 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- ...

contracture In pathology, a contracture is a shortening of muscles, tendons, skin, and nearby soft tissues that causes the joints to shorten and become very stiff, preventing normal movement. A contracture is usually permanent, but less commonly can be temp ...

s, arachnodactyly,

camptodactyly Camptodactyly is a medical condition that causes one or more Digit (anatomy), digits (fingers or toes) to be permanently bent. It involves fixed Human anatomical terms#Types of movement, flexion deformity of the proximal interphalangeal articulat ...

, kyphoscoliosis 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 bubb ...

dysplastic

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

dextrocardia Dextrocardia () 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 towards the left. There are two main types of dextrocardia: dextrocardia of embryonic ...

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, micrognathia, cleft or high arched palate, low-set ears, arachnodactyly, chest deformation as pectus, kyphoscoliosis 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 malformation in fetal development of the penis in which the urethra does not open from its usual location on the head of the penis. It is the second-most common birth defect of the male reproductive system, affecting about ...

, omphalomesenteric duct, hypertrophic pyloric stenosis and duodenal bands, hypoplastic right lower lobe of the lung, displacement of the

larynx The larynx (), commonly called the voice box, is an organ (anatomy), organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal ...

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 Spinal column, spine as it occurs in the Thoracic spine, thoracic and sacrum, sacral regions. Abnormal inward concave ''lordotic'' curving of the Cervical spine, cervical and Lumba ...

scoliosis Scoliosis (: scolioses) is a condition in which a person's Vertebral column, spine has an irregular curve in the coronal plane. The curve is usually S- or C-shaped over three dimensions. In some, the degree of curve is stable, while in others ...

, 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. * Additional signs may include; micrognathia, high arched or cleft palate, low set ears, kyphoscoliosis. * 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, growth retardation, and

developmental delay The term developmental delay can refer to: *Global developmental delay, an umbrella term used when children are significantly delayed in two or more areas of development *Specific developmental disorder, a classification of disorders characterize ...

, whereas minor face anomalies are less noticeable as the patient grows older.

Cause

MWS is a

heterogeneous Homogeneity and heterogeneity are concepts relating to the uniformity of a substance, process or image. A homogeneous feature is uniform in composition or character (i.e., color, shape, size, weight, height, distribution, texture, language, i ...

, 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 (physical form and structure), its developmental processes, its biochemical and physiological propert ...

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 In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. ''Myopathy'' means muscle disease ( Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meaning implies that the primary defec ...

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 to ...

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 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 autosomes ...

, 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 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 The cilium (: cilia; ; in Medieval Latin and in anatomy, ''cilium'') is a short hair-like membrane protrusion from many types of eukaryotic cell. (Cilia are absent in bacteria and archaea.) The cilium has the shape of a slender threadlike proj ...

structures of the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...

. These

organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...

s are present in many cellular types throughout the

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

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 with microcephaly Syndromes affecting the nervous system Syndromes affecting the eye Syndromes affecting the heart Syndromes affecting the kidneys Cardiology