Hereditary hypotrichosis of the scalp.

Hypotrichosis of the scalp was found in 4 individuals of a 6-generation Caucasian family. This congenital phenomenon is a rather rare subtype of hereditary hypotrichosis and affects only scalp hair. The hairs of the scalp were generally sparse and short vellus type from childhood and thinned progressively with age. Morphologic studies showed poor imbrication of cuticles and dysplastic bulbar structure of the anagen follicles. The density of hair follicles per/cm2 area was comparatively lower than that of normal individuals. The genealogical study and histomorphometrical findings of this autosomal dominant trait are discussed along with previously reported causes of hypotrichosis.

DNA polymerase alpha defect in the N syndrome.

The N syndrome is characterized by mental retardation, malformations, chromosome breakage, and development of T-cell leukemia (Opitz et al.: Proceedings of the II International Congress IASSMD pp 115-119, 1971; Hess et al.: Clinical Genetics 6:237-246, 1974b, American Journal of Medical Genetics [supplement] 3:383-388, 1987). N syndrome fibroblasts were studied to see if the high chromosome breakage rate associated with this apparently X-linked syndrome could be related to a deficiency of DNA polymerase alpha, a product of a gene localized to the X chromosome. Bleomycin, which is known to break double-stranded DNA, produced increased chromosome breakage in normal control, Fanconi anemia, and N syndrome fibroblasts. When aphidicolin was used to inhibit repair mediated by DNA polymerase alpha, both normal control and Fanconi anemia fibroblasts showed significantly more chromosome breakage than was produced by bleomycin alone, but there was no increase in the amount of breakage seen in the N syndrome fibroblasts over that seen with bleomycin alone. This suggests that the N syndrome is due to a mutation affecting the region of the X chromosome on which the gene for DNA polymerase alpha is located, and that the high risk of T-cell leukemia observed in the hemizygote is due to this DNA repair defect.

Apparent Prader-Willi phenotype in a woman with ring chromosome 9.

A 25-year-old mentally retarded woman was evaluated because of her socially inappropriate behavior. She had a phenotype so closely resembling that of the Prader-Willi syndrome that several experienced clinical geneticists immediately identified her as having that condition. Chromosome analysis showed a ring chromosome 9 but no apparent abnormality of chromosome 15.

Updating the N syndrome: occurrence of lymphoid malignancy and possible association with an increased rate of chromosome breakage.

Further studies on a family with the N syndrome, a multiple congenital anomaly/mental retardation syndrome first described by Hess et al in 1974, showed increased chromosome breakage in the affected brothers and in their unaffected mother, all 3 of whom died of lymphoid malignancy. It is suggested that the N syndrome is the result of an X-linked recessive mutation that produces a characteristic MCA/MR syndrome and chromosome instability. We postulate that this chromosome instability in the lymphoid cells of hemizygotes and in approximately half of the lymphoid cells of the heterozygote predisposes to a specific form of lymphoid malignancy.