Interstitial deletion 4q32-34 with ulnar deficiency: 4q33 may be the critical region in 4q terminal deletion syndrome

Abstract

We report on an infant with Robin sequence; mild developmental delay; a left ulnar ray defect with absent ulna and associated metacarpals, carpals and phalanges; and a right ulnar nerve hypoplasia. He had a de novo interstitial deletion of 4q32-->q34. The critical region involved in the 4q terminal deletion syndrome may be 4q33. This conclusion was suggested by showing that del(4)(q31qter), del(4)(q32qter), and del(4)(q33qter) result in a similarly severe phenotype. In addition, we propose that genes for distal arm development, in particular for development of the left ulnar ray, central nervous system development, and cleft lip and palate, may be located at 4q33.

The tale of a nail sign in chromosome 4q34 deletion syndrome

“…The main features include cardiac malformations, Robin sequence, microcephaly, genitourinary anomalies, short stature, moderate or severe learning disability, fifth finger clinodactyly and a dysmorphic appearance. Deletions distal to 4q31 have been associated with a milder phenotype (Mitchell et al, 1981;Stamberg et al, 1982;Lin et al, 1988;Sarda et al, 1992;Keeling et al, 2001).…”

A Girl with del(4)(q33) And Occipital Encephalocele: Clinical Description And Molecular Genetic Characterization of A Rare Patient

“…Chromosomal deletion syndromes with slightly differing breakpoints and different phenotypes contribute to the localization of genes with specific functions. A review of the features reported in patients with del(4)(q32), del(4)(q33), and del(4)(q34) showed that there was a clear difference in the frequency and severity of anomalies in children with either of these deletions (Keeling et al 2001). In their review of 4q deletions, Lin and co-workers (1988) compared 2 new patients with del(4)(q32) with 2 cases of del(4)(q32) described by Rethore et al (1979) and Fryns et al (1981).…”

“…Three of them had a congenital heart defect and absent digital flexion creases, and 1 died at the age of 3 months. Other reports of patients with interstitial deletions inside the terminal region 4q may contribute to an understanding of genotype-phenotype correlations and to an identification of the critical region and the genes responsible for the main manifestations (Sarda et al 1992;Calabrese et al 1997;Robertson et al 1998;Keeling et al 2001;Strehle et al 2001;Giuffrè et al 2004).…”

“…The region 4q31q34 may be critical for most of the clinical phenotype (Lin et al 1988). Some authors propose that the critical region for the 4q terminal deletion syndrome is 4q33, and that genes involved in facial, limb, cardiac, and central nervous system development must reside on 4q33 (Keeling et al 2001). Most deletions occurred de novo and therefore carried a low recurrence risk (Strehle et al 2001).…”

4q34.1–q35.2 deletion in a boy with phenotype resembling 22q11.2 deletion syndrome

“…This syndrome is usually associated with growth retardation, mild to moderate mental retardation, craniofacial anomalies (microcephaly, low-set and malformed pinnae, short nose with a low nasal bridge and micrognathia), palatal, skeletal and fifth finger anomalies (clinodactyly, ulnar ray defects, stiff fifth finger with hypoplastic or tapering distal phalanx, hooked or volar nail), as well as urogenital and cardiovascular malformations (mostly atrial or ventricular septal defects) [1,11,17,30]. Several authors have suggested that the critical region for most of the 4q-common characteristics might be assigned to the 4q31-q34 interval [16,26,28,29]. Smaller terminal or interstitial deletions involving bands 4q34-q35 have also been described in several cases [2, 5-7, 10, 17, 24, 33-35].…”