Ohdo-Madokoro-Sonoda Syndrome with a De Novo MED12 Mutation

Ohdo syndrome is extremely rare and comprises a heterogeneous group of disorders characterized by intellectual disability (ID) and typical facial features, including blepharophimosis, ptosis, dental hypoplasia, hearing impairment and intellectual disability. So far, fewer than 30 patients have been reported with Ohdo syndrome, with a prevalence of 1/1 000 000. Most reported cases are sporadic, except the original cases of ohdo who described two affected sisters and a first cousin, suggesting autosomal recessive inheritance. Autosomal dominant, X-linked- and mithochondrial inheritance have also been suggested.

We report the case of a 5-year-old girl, born to healthy, non-consanguineous parents, with no other family members known to be affected by a similar disorder. She exhibited significant dysmorphic facial features, including blepharophimosis, dental hypoplasia, hypertélorism, rétrognatism, microcephaly, trigonocéphaly, microphthalmia, nasolabial furrow, badly hemmed ear, and a pointed palate. These features were associated with psychomotor and growth retardation of less than 2 Standard deviations. Using whole exome sequencing (WES), we discovered the variant NM_005120.3 (MED12):c.6352C>T(p.Gin2118Ter) in the heterozygous state and its absence in the parents, confirming the de novo nature of this variant, which is compatible with the diagnosis of ohdo syndrome due to a heterozygous mutation of the MED 12.