Ohdo Syndrome, X-Linked

A number sign (#) is used with this entry because X-linked Ohdo syndrome is caused by mutation in the MED12 gene (300188) on chromosome Xq13.

Clinical Features

Maat-Kievit et al. (1993) described a boy (patient 2) with low weight, blepharophimosis, ptosis, wide depressed nasal bridge, long flat philtrum, thin vermilion, microstomia, micrognathia, cryptorchidism, scrotum hypoplasia, joint hyperextensibility, clinodactyly, overriding third toes, cafe-au-lait spots, developmental delay, deafness, and feeding problems. The authors diagnosed the patient with Ohdo blepharophimosis syndrome.

Verloes et al. (2006) reported the 9-month-old maternal nephew of the patient reported by Maat-Kievit et al. (1993), who had died at age 25 years of metastatic carcinoma. The nephew had a similar phenotype. Verloes et al. (2006) classified the disorder in these patients as a distinct blepharophimosis-mental retardation syndrome, MKB (Maat-Kievit-Brunner) type, and suggested X-linked inheritance. They noted that whereas the MKB phenotype in infancy resembled that of the SBBYS variant of Ohdo syndrome (603736), the phenotype in adulthood was clearly distinct, with coarse facial features, thick alae nasi, triangular face, and a different gestalt from that in the SBBYS type.

Molecular Genetics

Vulto-van Silfhout et al. (2013) performed exome sequencing in 2 families segregating X-linked Ohdo syndrome, including the family originally studied by Maat-Kievit et al. (1993) and another family with 2 affected males, and identified hemizygous missense mutations in the MED12 gene (300188.0003-300188.0004) that segregated with the disorder in each family. By analysis of an additional cohort of 9 simplex male patients with Ohdo syndrome, they identified another MED12 missense mutation (300188.0005) in 1 patient.