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A rare developmental defect during embryogenesis characterized by multiple joint contractures (arthrogryposis), a mask-like face with blepharophimosis, micrognathia, high-arched or cleft palate, low-set ears, decreased muscular bulk, kyphoscoliosis and arachnodactyly.
ORPHA:2461Classification level: Disorder
The prevalence is still unknown but to date between 30-50 cases have been described in the world literature.
The typical age of onset lies in the neonatal or infancy period and clinically Marden-Walker syndrome (MWS) is characterized by postnatal growth retardation and multiple joint contractures associated with restricted mobility of the joints. Facial dysmorphism includes a mask-like and asymmetric face along with blepharophimosis, low-set ears, high arched or cleft palate, micrognathia, short neck, and decreased muscular bulk. Other common features are kyphoscoliosis, pectus excavatum or carinatum, limited motor function in the shoulder, elbow and wrist joints and arachnodactyly and camptodactyly. Congenital talipes equinovarus, absent deep tendon reflexes and limbs with hypoplastic muscles are generally observed. Hypospadias with bilateral inguinal hernia may be observed. Minor cerebral malformations, cardiovascular or renal anomalies and intellectual deficit have also been described.
The underlying pathological mechanism of MWS has not yet been clearly established, but it is assumed that it is a developmental disorder of the central nervous system.
The diagnosis of MWS is based on the minimal criteria (postnatal growth retardation, severe developmental retardation, multiple joint contractures, a 'mask-like' face with blepharophimosis, micrognathia, high-arched or cleft palate, low-set ears and (kyphoscoliosis). Magnetic resonance imaging (MRI) of the head and an echocardiography may reveal cerebral malformations and cardiovascular abnormalities respectively. Kyphosis is diagnosed using X-ray imaging.
Differential diagnosis includes trisomy 13 and 18, Smith-Lemli-Opitz syndrome, Zellweger syndrome, spinal cord injury, amyoplasia congenita, infantile spinal muscular atrophy, Moebius syndrome, congenital hypomyelinating neuropathy, blepharophimosis-intellectual deficit syndromes, Van den Ende-Gupta syndrome, Freeman-Sheldon syndrome, Schwartz-Jampel syndrome (same clinical presentation but MWS lacks myotonia), infantile neuronal degeneration and focal infantile spinal muscular atrophy.
Prenatal diagnosis of MWS in a fetus with a previously affected sibling may be achieved by finding intrauterine growth retardation and renal cystic disease. Moreover, arthrogryposis can be viewed antenatally on ultrasound from the second trimester onwards. Ultrasonographic examination may also indicate an oligohydramnios. The finding of the latter should encourage a more detailed ultrasonographic examination, as ankylosed joints can be detected in utero.
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.
Management and treatment
The treatment of MWS is symptomatic with multidisciplinary management. Conservative orthopedic treatment and physiotherapy are indicated.
Intellectual deficit observed in MWS remains severe but contracture is not progressive and decreases with advancing age and physiotherapy. The long term prognosis is limited in many patients due to complications e.g. skeletal deformities, lung infections and gastrointestinal problems.