title: Clinical and genetic study of two patients with Zimmermann-Laband syndrome and literature review.
abstract: Zimmermann-Laband syndrome (ZLS) is a rare MCA/MR condition mainly characterized by gingival hypertrophy, hypo/aplastic nails and distal phalanges, hypertrichosis and intellectual disability. The molecular basis of ZLS is unknown. Most patients are sporadic, although familial aggregation is also observed with different inheritance patterns. We report on two unrelated children with full-blown characteristics of ZLS. Remarkable variability in expression included severity of neurocognitive involvement and extent of appendicular and facial features. In both, comparative genome hybridization array at a ~ 75 Mb resolution resulted negative, while aminoacid metabolic screening revealed high plasma levels of hypoxanthine and xanthine in one. Literature review identified 50 previously published patients (27 females, 23 males), including 14 familial, clustered in four pedigrees, and 37 sporadic. Tabulation of clinical features confirmed the core phenotype and identified developmental delay as the unique major clinical problem (occurring in 40% of the cases) with a moderately high risk of epilepsy (13%). Segregation analysis in the 20 sporadic patients with available data on healthy sibs and a single pedigree with affected sibs was significantly in contrast with an autosomal recessive mutation. An autosomal dominant mutation with high mutation rate and rare instances of germinal mosaicism seems the most likely inheritance pattern. This work may represent a starting point for future molecular studies aimed at identifying the molecular basis of ZLS.
authors.affiliation: Division of Medical Genetics, Department of Molecular Medicine, Sapienza University, San Camillo-Forlanini Hospital, Rome, Italy. Electronic address: mcastori@scamilloforlanini.rm.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Castori
authors.forename: Michele
authors.initials: M
authors.lastname: Valiante
authors.forename: Giulia
authors.initials: G
authors.lastname: Pascolini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Leuzzi
authors.forename: Antonio
authors.initials: A
authors.lastname: Pizzuti
authors.forename: Paola
authors.initials: P
authors.lastname: Grammatico
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging* / Q000235:genetics; D002675:Child, Preschool; D019465:Craniofacial Abnormalities / Q000000981:diagnostic imaging* / Q000235:genetics; D005260:Female; D005351:Fibromatosis, Gingival / Q000000981:diagnostic imaging* / Q000235:genetics; D056726:Genetic Association Studies; D006228:Hand Deformities, Congenital / Q000000981:diagnostic imaging* / Q000235:genetics; D006801:Humans; D008297:Male; D009030:Mosaicism; D010375:Pedigree; D011859:Radiography
keywords: Gingival overgrowth; Hirsutism; Hypertrichosis; Inheritance; Mental retardation; Nail dysplasia