Genotype-Phenotype Characterization of Wolf-Hirschhorn Syndrome Confirmed by FISH: Case Reports

Abstract

The Wolf-Hirschhorn syndrome (WHS) is a multiple malformation and contiguous gene syndrome resulting from the deletion encompassing a 4p16.3 region. A microscopically visible terminal deletion on chromosome 4p (4p16→pter) was detected in Case 1 with full blown features of WHS. The second case which had an interstitial microdeletion encompassing WHSC 1 and WHSC 2 genes at 4p16.3 presented with less striking clinical features of WHS and had an apparently “normal” karyotype. The severity of the clinical presentation was as a result of haploinsufficiency and interaction with surrounding genes as well as mutations in modifier genes located outside the WHSCR regions. The study emphasized that an individual with a strong clinical suspicion of chromosomal abnormality and a normal conventional cytogenetic study should be further investigated using molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH) or array-comparative genomic hybridization (a-CGH).

Wolf-Hirschhorn Syndrome: Clinical and Genetic Study of 7 New Cases, and Mini Review

“…Thus, it falls in the category of average size deletions (5 to 18 Mb). The clinical features of this specific case are similar to the ones found in a case report of a much younger girl (8 months old), both reporting impairments of the auditory system, microcephaly, coloboma, congenital heart defects, and delayed development which are considered to be some of the diagnostic markers for WHS [11]. Case 7 is part of the third category of deletions in WHS, having a 22 Mb deletion-46,XX,del(4)(p15.2-pter).…”

Wolf-Hirschhorn Syndrome (WHS), A Case Report and Review of Literature Submit Manuscript

“…Genetic counseling provides families with information on the nature and implications of inherited genetic disorders, as a means of facilitating shared health care decisions. [1][2][3][4]. "Its frequency is estimated as 1/50,000-1/20,000 births, with a female predilection of 2:1" [5].…”

Severe short stature and Wolf-Hirschhorn syndrome: response to growth hormone in two cases without growth hormone deficiency

“…It results from the hemizygous deletion encompassing the 4p16.3 region. It is estimated to be de novo in 50–60% of cases, with the rest due to an unbalanced translocation [ 2 ]. This critical region of 4p16.3 has been localized to an interval of 300–600 kb [ 3 ], involving genes that are believed to play an important role in DNA repair [ 4 , 5 ].…”