Interstitial and terminal deletions of the long arm of chromosome 4: Further delineation of phenotypes

Abstract

We reviewed 45 patients with a deletion of the long arm of chromosome 4. Forty-one were previous reports (25 terminal deletions and 16 interstitial deletions) and 4 are new cases with terminal deletions. Of the 29 patients with terminal deletions, 18 with deletion at 4q31 and 4 at 4q32----qter had an identifiable phenotype consisting of abnormal skull shape, hypertelorism, cleft palate, apparently low-set abnormal pinnae, short nose with abnormal bridge, virtually pathognomonic pointed fifth finger and nail, congenital heart and genitourinary defects, moderate-severe mental retardation, poor postnatal growth, and hypotonia. Six patients with a deletion at 4q33 and one patient with deletion 4q34 were less severely affected. In general, patients with various interstitial deletions proximal to 4q31 had a phenotype that was less specific, although mental retardation and minor craniofacial anomalies were also present. There were 3 patients with piebaldism and one with Rieger syndrome. We conclude that terminal deletion of chromosome 4q (4q31----qter) appears to produce a distinctive malformation (MCA/MR) syndrome in which the phenotype correlates with the amount of chromosome material missing and which differs from the more variable phenotype associated with interstitial deletions of 4q.

A New Inherited Interstitial Deletion of the Distal Long Arm of Chromosome 4,

“…The reported terminal 4q deletions mostly involved breakpoints at 4q31 (22 patients) [4, 5, 6, 7, 8], 4q32 (4 patients) [5, 9], 4q33 (12 patients) [10, 11, 12]and 4q34 (5 patients) [4, 5, 13]. Most interstitial deletions of the long arm of the chromosome 4 involve the q11–q31 segments.…”

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report

“…In order to establish a genotype-phenotype correlation, the severity of the phenotype is correlated with the size of the deletion. Thus, several reports suggested that small terminal, or interstitial, distal Cr4q del involving bands 4q34 and 4q35 seems to have little clinical impact, consisting in little facial dysmorphism and mild, or absent, intellectual disability (ID) 4 , and Yakut et al 5 reported a case of a familial interstitial 4q35 deletion with no discernible phenotypic effects. On the other hand, a relatively constant phenotype can be recognised in 4q31 to qter deletion.…”

Cardiac phenotypes in chromosome 4q− syndrome with and without a deletion of the dHAND gene

“…1,14,15 In particular, there appears to be a karyotypephenotype correlation because CVM has been noted in almost two thirds of patients with the terminal deletions at 4q31, whereas only about a quarter of patients with the more distal deletions at 4q34 or q35 have CVM. It has been postulated that genes distal to 4q34 may play a critical role in producing a CVM, 14 though the molecular basis is unknown.…”

“…Over the past 30 years, 50 cases have been reported, 23 (41%) of which have had a cardiovascular malformation (CVM). [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Compared with the 10% frequency in the Baltimore-Washington Infant Study, a case-control study of liveborn infants with a confirmed CVM in 1981-1989, 14 right ventricular outflow tract obstructive defects are more common (35%) in patients with 4q deletion.…”