Pterygia, Mental Retardation, And Distinctive Craniofacial Features

A number sign (#) is used with this entry because the disorder is caused by a chromosomal aberration.

In a systematic survey of the mentally retarded, Haspeslagh et al. (1985) identified 3 females, related as first or second cousins, with a seemingly unique syndrome. They were short of stature and had an unusual combination of craniofacial features: trigonocephaly, bulging forehead, flat face, and microretrognathia. All 3 had genital hypoplasia and 1 had multiple pterygia. Some of the same facial features were noted in 2 sisters, 1 the grandmother of 2 of the patients and the other the grandmother of the third. There were some 9 other presumably affected persons in the kindred, including some males. The pedigree pattern was consistent with dominant inheritance with incomplete penetrance. There was no instance of male-to-male transmission. Even though multiple pterygia occurred in only 1 index case, the authors suggested that this is a key feature of the full-blown MCA/MR (multiple congenital anomalies-mental retardation) syndrome present in the others in somewhat milder form. Schrander-Stumpel et al. (1988) reported a fourth unrelated case born of healthy, nonconsanguineous parents, both of whom were 30 years old at the time of the birth. They emphasized that severe mental retardation appears to distinguish this syndrome from the other multiple pterygium syndromes. However, van Bever and Hennekam (1995) described an adult female with features suggesting the Haspeslagh syndrome but without severe mental retardation and pterygia. Schrander-Stumpel et al. (1995) provided clinical follow-up of their patient.

Devriendt et al. (2000) restudied the family reported by Haspeslagh et al. (1985). High resolution karyotype after G- and T-banding revealed partial monosomy for distal chromosome 9p and partial trisomy for distal chromosome 6q in the original 3 patients. This was the unbalanced result of a balanced reciprocal translocation of distal 9p;6q. Devriendt et al. (2000) confirmed these cytogenetic findings by FISH, using subtelomeric probes for chromosomes 9p and 6q. Two additional affected children were found in the family. One, a 6.5-year-old boy, had the same unbalanced reciprocal translocation, inherited from his father. The other, a 2.5-year-old girl, carried the complementary reciprocal translocation, with partial monosomy of distal chromosome 6q and partial trisomy of distal chromosome 9p, inherited from her mother. This report confirmed that small chromosomal aberrations, difficult to detect by standard cytogenetic techniques, may cause familial private syndromes.