HIRSCHSPRUNG-DISEASE, MICROCEPHALY, MENTAL-RETARDATION, AND CHARACTERISTIC FACIAL FEATURES - DELINEATION OF A NEW SYNDROME AND IDENTIFICATION OF A LOCUS AT CHROMOSOME 2Q22-Q23

We have identified six children with a distinctive facial phenotype in association with mental retardation (MR), microcephaly, and short sta ture, four of whom presented with Hirschsprung (HSCR) disease in the n eonatal period. HSCR was diagnosed in a further child at the age of 3 years after investigation for severe chronic constipation and another child, identified as sharing the same facial phenotype, had chronic co nstipation, but did not have HSCR. One of our patients has an intersti tial deletion of chromosome 2, del(2)(q21q23). These children strongly resemble the patient reported by Lurie et al with HSCR and dysmorphic features associated with del(2)(q22q23). All patients have been isola ted cases, suggesting a contiguous gene syndrome or a dominant single gene disorder involving a locus for HSCR located at 2q22-q23. Review o f published reports suggests that there is significant phenotypic and genetic heterogeneity within the group of patients with HSCR, MR, and microcephaly. In particular, our patients appear to have a separate di sorder from Goldberg-Shprintzen syndrome, for which autosomal recessiv e inheritance has been proposed because of sib recurrence and consangu inity in some families.