Search

We report on a clinical-genetic study of 16 Wolf-Hirschhorn syndrome (WHS) patients. Hemizygosity of 4p16.3 was detected by conventional prometaphase chromosome analysis (11 patients) or by molecular probes on apparently normal chromosomes (4 patients). One patient had normal chromosomes without a detectable molecular deletion within the WHS "critical region." In each deleted patient, the deletion was demonstrated to be terminal by fluorescence in situ hybridization (FISH). The proximal breakpoint of the rearrangement was established by prometaphase chromosome analysis in cases with a visible deletion. It was within the 4p16.1 band in six patients, apparently coincident with the distal half of this band in five patients. The extent of each of the four submicroscopic deletions was established by FISH analyses with a set of overlapping cosmid clones spanning the 4p16.3 region. We found ample variations in both the size of the deletions and the position of the respective breakpoints. The precise definition of the cytogenetic defect permitted an analysis of the genotype-phenotype correlations in WHS, leading to the proposal of a set of minimal diagnostic criteria, which in turn may facilitate the selection of critical patients in the search for the gene(s) responsible for this disorder. We observed that genotype-phenotype correlations in WHS mostly depend on the size of the deletion, a deletion of <3.5 Mb resulting in a mild phenotype, in which malformations are absent. The absence of a detectable molecular deletion is still consistent with a WHS diagnosis. Based on these observations a "minimal" WHS phenotype was inferred, the clinical manifestations of which are restricted to the typical facial appearance, mild mental and growth retardation, and congenital hypotonia., (Copyright 2000 Wiley-Liss, Inc.) more...

We report on a 17 6/12-year-old boy with nephronophthisis, retinitis pigmentosa, left upper eyelid ptosis, enopthalmos, transmissive deafness, GH and TSH deficiency, and mild skeletal dysplasia. A similar case was reported by Bianchi et al. [1988: Helv Paediatr Acta 43:449-455] in another Italian patient. Here we confirm the previous observations and argue that both patients might be affected by a new syndrome. more...

We report on 2 unrelated patients with Costello syndrome. The first is a 5-year-old girl with "coarse" face, nasal papillomata, redundant skin of feet and hands, hyperextensible hand and finger joints, curly hair, feeding problems due to oral motor apraxia, growth and psychomotor retardation. The second is a 3-year-old boy with "coarse" face, loose skin on hands and feet, curly hair, oral motor apraxia, severe growth and psychomotor retardation. In both patients urine sialic acid levels were found to be repeatedly high. The meaning of this biochemical abnormality is discussed. more...