The 4p—Syndrome

Unbalanced 4;6 translocation and progressive renal disease

“…Wolf-Hirschhorn syndrome results from deletion of part of the short arm of chromosome 4; the critical region has been defined as a 165-kb region within 4p16.3, 2.31 Mb from the 4p terminus [Wright et al, 1997]. This condition is thought to be a contiguous gene syndrome characterized by prenatal and postnatal growth deficiency, severe mental retardation, seizures, microcephaly, and facial characteristic including high arched eyebrows, hypertelorism, a broad flattened nose, down-turned "carp-like" mouth, micrognathia, simple low-set abnormally modeled ears [Pierpont, 1996;Lurie et al, 1980;Guthrie et al, 1971]. Other abnormalities may include eye defects, cleft lip or palate, congenital heart abnormalities, renal hypoplasia, hypospadias, and other visceral anomalies [Zellweger et al, 1975].…”

Translocation of chromosome 4 and 9 with ring formation of chromosome 4 short arm.

“…Ring formation following a translocation implies the occurrence of a third break after the translocation, in this case at the distal portion of the short arm of 4, with subsequent fusion of the broken ends at q12 and pl?6. The exact distal break point could not be accurately identified, but is presumed to be terminal because of the size of the ring and the minimal physical abnormalities in comparison with the gross phenotypic abnormality described in Wolf's 4p-syndrome (Guthrie et al, 1971). The typical clinical features of this syndrome are thought to be associated with loss of the 4pl6 band (Rethore, 1977).…”

A genome-wide deletion map in 125,730 individuals for novel rare disease gene and variant discovery

“…Structural variants (SVs) represent a diverse group of genomic alterations, encompassing deletions, duplications, insertions, inversions, translocations, and complex combinations that may occur concurrently within a single mutational event 9 . SVs are implicated in a diverse spectrum of genetic disorders; germline SVs are a frequent cause of rare disease 10,11 , while somatic SVs (e.g. translocations creating a pathogenic fusion gene) are a common driver event in some cancers 12,13 .…”