Chromosome 18p Deletion Syndrome

A number sign (#) is used with this entry because it represents a contiguous gene deletion syndrome.

Clinical Features

The 18p- syndrome was first described in 1963 by de Grouchy et al. (see de Grouchy and Turleau, 1984). The main clinical manifestations are mental retardation, growth retardation, craniofacial dysmorphism including round face, dysplastic ears, wide mouth and dental anomalies, and abnormalities of the limbs, genitalia, brain, eyes, and heart. Tsukahara et al. (2001) noted that the round face characteristic in the neonatal period and childhood may change to a long face with linear growth of the height of the face.

Buhler et al. (1964) reported an early case of 18p- syndrome. In addition to the typical manifestations of that syndrome, the girl had an abnormality of thyroxine synthesis, most likely a coupling defect (Buhler, 1983). Since the proband was the youngest of 7 sibs and none of the other sibs had a thyroxine defect, Buhler (1983) suggested that the deletion may have 'uncovered' a heterozygous mutation inherited from 1 parent and that the gene locus is on the short arm of chromosome 18.

Three patients with 18p- syndrome and hypopituitarism have been reported (Leisti et al., 1973; Buffoni et al., 1976; Artman et al., 1992), suggesting that a factor on chromosome 18 may in some way be involved. In the patient reported by Artman et al. (1992), MRI scan of the brain showed hypoplasia of the hypothalamus and pituitary gland.

Although most reported cases have been sporadic, Tsukahara et al. (2001) reported a family in which a mother and her son and daughter were affected. They cited 2 other familial cases reported by Uchida et al. (1965) and Velagaleti et al. (1996).

Wester et al. (2006) examined 7 patients with de novo 18p terminal deletions. Genotype-phenotype analysis revealed that the 4 patients with deletions located in the centromeric region at 18p11.1 had mental retardation, whereas of 3 patients with breakpoints distal to 18p11.1 (18p11.22-p11.21), 2 had normal intelligence and 1 had borderline mental retardation, suggesting that a critical region for mental retardation may exist between 18p11.21 and 18p11.1. All of the patients with a breakpoint at 18p11.1 had a broad face, which was seen in only 1 of the patients with a more distal breakpoint. Muscular hypotonia was very common (6 of 7 patients). Wester et al. (2006) noted that slowness of motion and action was more of a problem to some study participants than mental retardation. Language performance was more delayed than mental performance, and the majority had major speech problems.