Cree Mental Retardation Syndrome

Clinical Features

Khalifa et al. (2002) described 3 Canadian brothers of First Nation Canadian (Cree) origin with a previously undescribed pattern of malformations including distinctive craniofacial abnormalities with triangular facies, hypertelorism, low-set and posteriorly rotated ears, ocular colobomas, ptosis, brachycephaly with widely separated sutures, cleft soft palate, undescended testes, bifid scrotum and hypospadias, wide webbed neck, webbed fingers, pectus excavatum and hypersegmented sternum, and severe psychomotor retardation. The presence of normal brain imaging and physical growth distinguished this syndrome from other syndromes with overlapping abnormalities. Either X-linked or autosomal recessive inheritance was considered possible.

Chodirker et al. (2002) considered the patients reported by Khalifa et al. (2002) to have the same disorder as that in the 8 aboriginal Canadians from Manitoba and Ontario reported as having Ritscher-Schinzel syndrome (RSS; 220210) by Marles et al. (1995). Thus they believed that the debate was not about whether or not the cases described by Khalifa et al. (2002) represented a 'new' syndrome, but whether or not the cases described in these 2 reports should be considered to have RSS or a separate 'new' syndrome first reported by Marles et al. (1995).

In a rebuttal, Khalifa and Cappon (2002) argued that the patients of Marles et al. (1995) were phenotypically distinct from those they reported in the same ethnic group; furthermore, they questioned the diagnosis of RSS in their own patients because they did not fulfill the criteria for RSS, also known as the 3C syndrome because of cerebellar, cardiac, and characteristic craniofacial anomalies. Their patients had no cerebellar or other structural central nervous system abnormalities or significant cardiac anomalies, with the exception of a small ventricular septic defect in 1. The craniofacial changes were different from those of RSS.