Marshall syndrome

Definition: Marshall syndrome is a multisystem disease characterized by ocular abnormalities, sensorineural hearing loss, craniofacial anomalies and anhidrotic ectodermal dysplasia.

It has been reported in about 12 families, each of them with at least two affected members.

Affected individuals have a short stature, brachycephaly, and facial dysmorphia (hypertelorism, epicanthal folds, flat nasal bridge, anteverted nostrils, flat midface, micrognathia, long philtrum, thick lips and sometimes cleft palate with or without Robin sequence). The upper incisors are prominent.

Sensorineural anomalies include hearing loss, myopia, cataract and other, less common, eye anomalies such as vitreoretinal degeneration, retinal detachment, glaucoma, and lens dislocation.

Marshall syndrome patients have a thick calvaria, abnormal frontal sinuses, and intracranial calcifications. The eyeballs appear large, possibly because of a shallow orbit.

Symptomatic osteoarthritis, beginning in the fourth or fifth decade of life and affecting the knees and lumbosacral spine, has also been observed, as well as mild hypotrichosis and hypohidrosis in some patients.

The syndrome is inherited as an autosomal dominant trait.

The Marshall syndrome phenotype maps to the chromosome 1p21 region and is caused by a mutation in the collagen XI, alpha-1 polypeptide gene (COL11A1).

Radiological findings include hypoplasia of the maxilla, nasal bones, and frontal sinuses, calvarial thickening, intracranial calcifications, and narrowed joint spaces, with osteophytic arthropathy in the hips and knees.

Marshall syndrome shares several clinical characteristics with Stickler syndrome but the mutations responsible for these syndromes are not identical: although mutations in the COL11A1 gene were identified in both syndromes, no defect in the COL2A1 gene causing Stickler syndrome has been found in patients with Marshall syndrome.

Prenatal diagnosis is possible by screening for mutations in the COL11A1 gene.

Credits

 ORPHA560