Glass et al. (1989) reported a 16-year-old boy with severe mental retardation, microcephaly, and craniofacial dysmorphism associated with an interstitial deletion of chromosome 2q32.2-q33.1. He had no comprehensible speech and was totally dependent for all activities. Facial features included large beaked nose, ptosis, and cleft palate. He also had seizures and a striking scalloped skin pigmentation that did not follow Blaschko lines. Activity of isocitrate dehydrogenase (IDH1; 147700) was normal.

Van Buggenhout et al. (2005) reported 4 unrelated patients with interstitial deletions of chromosome 2q32-q33. Common clinical features included pre- and postnatal growth retardation, severe mental retardation, thin and sparse hair, persistent feeding difficulties, inguinal hernia, and broad-based gait. Facial features included high long face, high forehead, ptosis, dacrocystitis, high nasal bridge, small mouth, teeth abnormalities, micrognathia, and cleft or high-arched palate. Two patients had seizures, and 3 had spasticity and contractures. Three patients had a specific behavioral phenotype with hyperactivity and motor restlessness, chaotic behavior, and happy personality intermixed with periods of aggression and anxiety, sleeping problems and self-mutilation. Array CGH and FISH analysis showed that all patients shared an 8.1-Mb minimal deleted region. The cleft or high-arched palate most likely resulted from hemizygosity for the SATB2 gene (608148).

Rosenfeld et al. (2009) reported 3 unrelated patients with small heterozygous deletions of chromosome 2q33.1, ranging from 173.1 to 185.2 kb, that affected only the SATB2 gene. Parental samples from the mother were available for only 2 patients, and neither mother carried the deletion; parental samples were not available for the third patient. All patients had severe developmental delay, mental retardation, and tooth anomalies, but other features varied. Dentofacial anomalies included delayed primary dentition and micrognathia in 1 patient; cleft palate, crowded teeth, and small mandible in the second; and fused mandibular central incisors without cleft palate in the third. Two patients had behavioral abnormalities and mild dysmorphic features. Rosenfeld et al. (2009) concluded that haploinsufficiency for SATB2 is responsible for some of the clinical features associated with the 2q32-q33 deletion syndrome.

Urquhart et al. (2009) reported a girl with a de novo heterozygous 4.5-Mb microdeletion of chromosome 2q33.1. She had cleft soft palate, feeding problems, febrile seizures, and delayed psychomotor development with poor speech. She was mildly dysmorphic, with broad forehead, flat philtrum, small mouth, thin upper lip, missing lateral incisors, and relative macrocephaly, but ears were normal. She also had joint laxity, valgus foot deformity, broad toes and thumbs, brachydactyly, and contractures of the fourth and fifth fingers. She had a social disposition. Brain MRI showed nonspecific periventricular white matter abnormalities. The deleted region included the SATB2 gene.

Rifai et al. (2010) reported a 16-year-old girl, born of unrelated French Caribbean parents, with an interstitial 26.3-Mb deletion of chromosome 2q31.2-q33.2. She had prenatal and postnatal growth retardation, microcephaly, facial dysmorphism, cleft palate, camptodactyly, bilateral talipes equinovarus, severe intellectual disability, and ectodermal anomalies. Ectodermal anomalies included thin, atrophic skin, sparse, brittle, slowly growing hair, oligodontia with abnormally shaped teeth, normal sweating, and normal fingernails. These findings were consistent with a diagnosis of ectodermal dysplasia. The deletion resulted in hemizygosity for the HOXD gene (see, e.g., HOXD1; 142987) cluster and its regulatory elements, which may affect limb development. Haploinsufficiency of other genes such as COL3A1 (120180)/COL5A2 (120190), GTF3C3 (604888), CASP8 (601763), CASP10 (601762), and SATB2 may also influence the phenotype.

Balasubramanian et al. (2011) reported 7 unrelated patients with different interstitial deletions of chromosome 2q33.1. The phenotype was variable, but common features included delayed psych