Ohdo Syndrome

Clinical Features

Ohdo et al. (1986) described the combination of mental retardation, congenital heart disease, blepharophimosis, blepharoptosis, and hypoplastic teeth in a brother and sister and in a daughter of their paternal aunt. They concluded that the disorder had not been reported before. Say and Barber (1987) and Biesecker (1991) reported cases. Maat-Kievit et al. (1993) reported 2 unrelated affected boys and compared their findings with those in 5 previously reported patients. Male patients had cryptorchidism and scrotal hypoplasia.

Lopes and Guion-Almeida (1997) described a case of Ohdo syndrome with the additional features of cleft palate and bladder diverticula.

Mhanni et al. (1998) reported vertical transmission of Ohdo syndrome from mother to son, suggestive of autosomal dominant inheritance. The possibility of X-linked or mitochondrial inheritance cannot be ruled out by this case. Taken together with the previously reported cases, the authors suggested that autosomal dominant inheritance with incomplete penetrance is most likely. Genetic heterogeneity is also possible.

Stoll (1999) described a possible case of Ohdo syndrome.

White et al. (2003) reported 2 cases of Ohdo syndrome, one with mild and the other with severe features, illustrating the phenotypic variability of the condition. The authors noted that all cases with the severe phenotype have been sporadic. Subtelomeric FISH studies of all chromosome arms on their 2 cases showed no abnormality.

Verloes et al. (2006) described 11 patients from 8 families with a blepharophimosis-mental retardation syndrome (BMRS) phenotype and suggested a classification of BMRS into 5 groups: Group 1, del(3p) syndrome (613792); Group 2, BMRS, Ohdo type, limited to the original patients of Ohdo et al. (1986); Group 3, BMRS, SBBYS type (603736), with distinctive dysmorphic features and variable anomalies including heart defect, optic atrophy, deafness, hypoplastic teeth, cleft palate, joint limitations, and hypothyroidism; Group 4, BMRS, MKB type (300895), with coarse, triangular face; and Group 5, BMRS, Verloes type (604314), with severe microcephaly, hypsarrhythmia, adducted thumbs, cleft palate, and abnormal genitalia.

Day et al. (2008) examined 8 unrelated patients with the Say-Barber-Biesecker-Young-Simpson type of Ohdo syndrome (SBBYSS; 603736) and reviewed the 25 previously reported patients reported with Ohdo syndrome. One family had a reported recurrence of the syndrome, resulting in pregnancy termination at 20 weeks' gestation. Day et al. (2008) stated that the most important clue to diagnosis is the facial gestalt and emphasized the severity of the psychomotor delay. Noting that 3 of their patients had thyroid abnormalities, they suggested that Ohdo and SYBBYS syndromes may be the same condition.

Clayton-Smith et al. (2011) described SBBYSS as a variant of Ohdo syndrome. In patients with SBBYSS, they identified heterozygous mutations in the KAT6B gene (605880); however, they did not study patients reported by Ohdo et al. (1986), Say and Barber (1987), or Biesecker (1991).