Phenotypic variations in wolf-hirschhorn syndrome

Abstract

Wolf-Hirschhorn syndrome (WHS) is a rare chromosomal disorder caused by terminal deletion of the short arm of chromosome 4. The clinical picture includes growth retardation, severe mental retardation, characteristic "Greek helmet" like face, seizures and midline defects in the brain, heart, palate and genitalia. Recently-used molecular techniques increase the number of diagnosed cases due to the detection of smaller deletions. The severity of the clinical presentation is variable depending on the haploinsufficiency of genes in a deleted region. We present six children with WHS with variable clinical appearance. The assessment of several elements (facial dysmorphism, mental retardation, additional congenital anomalies) provided classification into minor, mild or severe forms. Three of the children had a visible cytogenetic deletion on chromosome 4p, two had microdeletions detected with fluorescent in situ hybridization (FISH), and one child with a less characteristic clinical picture had a mosaic type of the deletion. Correlation between the clinical presentation and the length of the deleted region was confirmed.

Keywords: Fluorescent in situ hybridization (FISH); Microdeletion syndromes; Phenotype; Wolf-Hirschhorn syndrome (WHS).

Figure 1.

a) Facial appearance in our patients. b) Deep sacral dimple in patient 1; sandal gap in patient 6.

Figure 2.

Cytogenetically visible deletion of chromosome 4p in patient 2.

Figure 3.

Microdeletion of chromosome 4p detected by FISH in patient 5.