Marden-Walker syndrome (MWS) is a rare but disabling syndrome caused by connective tissue abnormalities affecting many tissues and organ systems. It is caused by a genetic defect.
The first signs appear in infancy, as retarded growth and delay in psychomotor milestones, with many associated anomalies. Intellectual improvement has not been observed, but contractures remain static, often showing much change following physiotherapy and as the child grows.
The physical features are characterized by congenital contractures of many joints leading to crippling deformations (arthogryposis), mask-like facies with blepharophimosis (narrowing of the eyelid aperture), micrognathia or an abnormally small mandible, a high arched palate, or a cleft palate, poor muscle bulk, and low-set ears. The child may also suffer from spinal deformities such as kyphoscoliosis. The joints are fixed in abnormal positions making movement slow and difficult.
Other symptoms include a smaller than normal head circumference, a low hairline, and a small mouth. There may be duodenal bands, pyloric stenosis, and malabsorption syndromes, with or without pancreatic insufficiency.
MWS affects more males than females, the ratio being 11:3, but less than 60 cases have been described so far the world over. The reason for this congenital disorder is as yet unknown, but involves maldevelopment of the central nervous system.
MWS is based upon the presence of the physical and mental criteria detailed above, such as growth retardation in postnatal life, severe intellectual disability and arthrogryphosis. Imaging may be required, such as magnetic resonance imaging of the head, echocardiography of the brain and the heart, and X-rays of the spine. Prenatal diagnosis is possible and is performed if there is an affected sibling.
Genetic counseling is offered to the parents of an affected child. The inheritance is autosomal recessive, and thus with each future pregnancy, there is a 25% chance that each parent will pass on one copy each of the defective gene (unidentified as yet) to the offspring, and a 50% chance that one parent will pass on one defective gene to the offspring, resulting in an affected child and a carrier, respectively. A few individuals with Marden syndrome have been found to have mutations in the PIEZO2 gene.
The affected child requires symptomatic management with the cooperation of a multidisciplinary team, including orthopedic correction and physiotherapy. The prognosis is not good when the patient has severe deformities or pulmonary complications.