Clark-Baraitser Syndrome

Clark and Baraitser (1987) described 2 mentally retarded brothers who also had macrocephaly, 'square' forehead, prominent supraorbital ridges, broad nasal tip, prominent lower lip, large ears, obesity, and macroorchidism.

Baraitser et al. (1995) described a family in which 2 male first cousins related through their mothers had features similar to those in the family reported by Clark and Baraitser (1987). The boys had nonspecific mental retardation with macrocephaly and obesity. The authors compared the disorder in both these families to the Atkin-Flaitz syndrome (300431) described by Atkin et al. (1985). The main difference at the clinical level lay in the short stature and hypertelorism of the Atkin-Flaitz patients. The obesity in both conditions suggested Prader-Willi syndrome (176270); however, there was never congenital hypotonia, early feeding difficulties, or nocturnal searching for food.

Monteiro de Pina-Neto and Andreotti de Molfetta (1998) reported a 14-year-old Brazilian boy, born to nonconsanguineous parents, who had mental retardation, macrocephaly, tall stature and large hands, obesity, square forehead, prominent supraorbital ridges, prominent lower lip, large ears, a gap between the central incisors, and normal eye spacing. CT scan of the brain showed macrocrania with no abnormalities of the brain. Bone age was compatible with chronologic age, and there were no inborn errors of metabolism. He had a normal karyotype by GTG banding. Macroorchidism that had been noted at age 10 disappeared after puberty.

Tabolacci et al. (2005) reported 2 brothers, born of nonconsanguineous parents, who had moderate to severe mental retardation, severe macrocephaly, obesity, characteristic face, big hands and feet, advanced bone age, and brain abnormalities, including frontal cortical atrophy. The height of both brothers, aged 24 and 15 years, respectively, was at the 10th centile, below the midparental target. They both exhibited autistic-like behavior in which they would stand still for several minutes with a fixed facial expression in an almost catatonic state; the parents also reported that they had a high pain threshold. FISH screening revealed a cryptic subtelomeric deletion of chromosome region 22q13 (see 606232), not present in either parent; segregation analysis showed the deletion to be of maternal origin, mostly likely to due germinal mosaicism. Tabolacci et al. (2005) suggested that patients diagnosed with Clark-Baraitser syndrome be tested for submicroscopic 22qter deletion.

Mendicino et al. (2005) described a 16-year-old boy, born of nonconsanguineous parents, who had moderate mental retardation associated with tall stature, obesity, macrocephaly, and typical facial features. The patient had behavior problems when thwarted, which the authors noted had been reported in 3 previous patients with Clark-Baraitser syndrome (see Baraitser et al., 1995 and Monteiro de Pina-Neto and Andreotti de Molfetta, 1998). The patient's mother and sister, who were of normal intelligence and had normally spaced eyes, both had a gap between their central upper incisors and a large forehead; the sister also had prominent supraorbital ridges, a broad nasal tip, thick lower lip, and microdontia of upper lateral incisors, and the mother was moderately obese. Subtelomeric chromosome analysis in the patient excluded cryptic rearrangements. Mendicino et al. (2005) suggested that the mild features in the female relatives of this patient might disclose a possible carrier condition and, in combination with the normal cytogenetic investigations, lend support to X-linked inheritance of this syndrome.