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

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.