Translocations involving 4p16.3 in three families: deletion causing the Pitt-Rogers-Danks syndrome and duplication resulting in a new overgrowth syndrome.

Abstract

Three families are reported who have a translocation involving 4pl6.3. Nine subjects are described with the clinical features of the Pitt-Rogers-Danks (PRD) syndrome confirming pre-and postnatal growth failure, microcephaly, severe mental retardation, seizures, and a distinctive facial appearance; a deletion of 4p16.3 was seen in all eight patients studied with fluorescence in situ hybridisation (FISH). Eleven subjects had a new syndrome with physical overgrowth, heavy facial features, and mild to moderate mental handicap; a duplication of the chromosome region 4p16.3 was found in the four subjects studied. It is suggested that the growth abnormalities in these two families may be explained by a dosage effect of the fibroblast growth factor receptor gene 3 (FGFR3), which is located at 4pl6.3, that is, a single dose leads to growth failure and a triple dose to physical overgrowth. We describe the molecular mapping of the translocation breakpoint and define it to within locus D4S43.

?Tandem? duplication of 4p16.1p16.3 chromosome region associated with 4p16.3pter molecular deletion resulting in Wolf-Hirschhorn syndrome phenotype

“…With a few exceptions [Bourouillou et al, 1978;Rolland et al, 1977;Sebastio et al, 1996], the associated trisomies did not have significant phenotypic effects [Lejeune et al, 1975;Martsolf et al, 1987;Partington et al, 1997;Stengel-Rutkowski et al, 1984;Tranebjaerg et al, 1984;Wheeler et al, 1995].…”

Interstitial 9q22.3 microdeletion: clinical and molecular characterisation of a newly recognised overgrowth syndrome

“…However, despite these recent advances, the pathogenesis of many overgrowth syndromes remains poorly understood. Interestingly, several chromosomal duplications and deletions, such as dup(4)(p16.3) and del (22)(q13), have also been associated with overgrowth, 4,5 indicating that some still unclassified overgrowth syndromes may be caused by subtle genomic imbalanced rearrangements.…”

Overgrowth and trisomy 15q26.1-qter including the IGF1 receptor gene: report of two families and review of the literature

“…Presumably, a detailed study of these unusual cases can give us a clue for candidate chromosome regions or genes involved in the pathogenesis of overgrowth. Four partial trisomies including growth-related genes have been seen in overgrowth syndromes, including trisomy 4p16.3 and the FGFR3 gene, 4 trisomy 11p15.5 and the IGF2 gene, 5 trisomy 20p11.2 and the SSTR4 gene 6 and trisomy 15q25-qter. 7 Overgrowth has been reported as well in association with tetrasomy 15q25-qter.…”