Polydactyly

Abstract: Pigmentary degeneration of the retina (retinitis pigmentosa) may appear as an isolated finding unassociated with other systemic abnormalities. Often, however, the patient may present other abnormalities, a number of which occur frequently enough in association with retinitis pigmentosa to be recognized as a syndrome. The Lawrence-Moon-Biedl syndrome, consisting of pigmentary degeneration of the retina, obesity, mental retardation, hypogenitalism, and polydactyly, is such an example. There also may be other less common abnormalities, such as deafness, convulsions, ophthalmoplegia, cerebellar ataxia, and progeria (premature aging) associated with retinitis pigmentosa. External ophthalmoplegia is one of the uncommoner abnormalities found associated with pigmentary degeneration of the retina. Barnard and Scholz1reported four cases of this association and concluded that the association was more than just coincidental. Walsh2agreed with them and stated that the association is not just fortuitous but rather represents a syndrome. He listed five cases that he had observed,

Abstract: To determine the interfamilial and intrafamilial variation in the expression of the Bardet-Biedl syndrome (a form of Laurence-Moon-Biedl syndrome), we looked for the five recognized features of the disorder (retinal dystrophy, obesity, polydactyly, mental retardation, and hypogonadism), plus possible renal manifestations, in some or all of 32 patients with this disorder. All 28 patients examined had severe retinal dystrophy, but only 2 had typical retinitis pigmentosa. Polydactyly was present in 18 of 31 patients, but syndactyly, brachydactyly, or both were present in all. Obesity was present in all but 1 of 25 patients. Only 13 of 32 patients were considered mentally retarded. Scores on verbal subtests of intelligence were usually lower than scores on performance tasks. Seven of eight men had small testes and genitalia, which was not due to hypogonadotropism. All 12 women studied had menstrual irregularities, and 3 had low serum estrogen levels (1 of these had hypogonadotropism, and 2 had primary gonadal failure). The remaining women who were of reproductive age had endocrinologic evidence of reproductive dysfunction. Diabetes mellitus was present in 9 of 20 patients. Renal structural or functional abnormalities were universal (n = 21), and three patients had end-stage renal failure. We conclude that the characteristic features of Bardet-Biedl syndrome are severe retinal dystrophy, dysmorphic extremities, obesity, renal abnormalities, and (in male patients only) hypogenitalism. Mental retardation, polydactyly, and hypogonadism in female patients are not necessarily present.

Abstract: Pallister-Hall syndrome (PHS, M146510) was first described in 1980 in six newborns. It is a pleiotropic disorder of human development that comprises hypothalamic hamartoma, central polydactyly, and other malformations. This disorder is inherited as an autosomal dominant trait and has been mapped to 7p13 (S. Kang et al. Autosomal dominant Pallister-Hall syndrome maps to 7p13. Am. J. Hum. Genet. 59, A81 (1996)), co-localizing the PHS locus and the GLI3 zinc finger transcription factor gene. Large deletions or translocations resulting in haploinsufficiency of the GLI3 gene have been associated with Greig cephalopolysyndactyly syndrome (GCPS; M175700) although no mutations have been identified in GCPS patients with normal karyotypes. Both PHS and GCPS have polysyndactyly, abnormal craniofacial features and are inherited in an autosomal dominant pattern, but they are clinically distinct. The polydactyly of GCPS is commonly preaxial and that of PHS is typically central or postaxial. No reported cases of GCPS have hypothalamic hamartoma and PHS does not cause hypertelorism or broadening of the nasal root or forehead. The co-localization of the loci for PHS and GCPS led us to investigate GLI3 as a candidate gene for PHS. Herein we report two PHS families with frameshift mutations in GLI3 that are 3' of the zinc finger-encoding domains, including one family with a de novo mutation. These data implicate mutations in GLI3 as the cause of autosomal dominant PHS, and suggest that frameshift mutations of the GLI3 transcription factor gene can alter the development of multiple organ systems in vertebrates.

Abstract: We report on six infants with a neonatally lethal malformation syndrome of hypothalamic hamartoblastoma, postaxial polydactyly, and imperforate anus Some, but not all, patients had laryngeal cleft, abnormal lung lobulation, renal agenesis and/or renal dysplasia, short 4th metacarpals, nail dysplasia, multiple buccal frenula, hypoadrenalism, microphallus, congential heart defect, and intrauterine growth retardation The infants also had hypopituitarism and hypoadrenalism All were sporadic cases, parents were not consanguineous, chromosomes were apparently normal Family histories were unremarkable There was insecticide and/or herbicide exposure in several of the cases, but no exposures were common to all 6 mothers Five of the patients were born within an 8-month period, but all in different geographic locations It is postulated that this is a previously apparently unreported syndrome of presently unknown cause