Chromosome 18 Pericentric Inversion

A number sign (#) is used with this entry because a chromosome 18 pericentric inversion can result in a recombinant dup(18p)/del(18q) or dup(18q)/del(18p) phenotype.

Cytogenetics

Mejia-Baltodano et al. (1997) reported a family in which the father had a large pericentric inversion of chromosome 18 (p11.2q22). The oldest daughter had a dup(18q)/del(18p) recombinant, whereas her younger sister and brother had a dup(18p)/del(18q) recombinant. The 2 younger sibs were more severely affected, with marked dysmorphic features, mental retardation, and developmental delay, whereas the older sister had only minor dysmorphic features and a cognitive delay of 2 years.

Vermeulen et al. (2005) described a family segregating a large pericentric inversion of chromosome 18, inv(18)(p11.22q23). Individuals heterozygous for the nonrecombinant inversion were unaffected. However, those heterozygous for either the dup(18p)/del(18q) or dup(18q)/del(18p) recombinant exhibited mild learning difficulty, personality disorders, and deficient social behavior, without mental retardation or dysmorphic features. Of the 3 family members tested, the behavioral abnormalities were more prominent in the 2 individuals with the dup(18p)/del(18q) recombinant than in the 1 with the dup(18q)/del(18p) recombinant. Vermeulen et al. (2005) suggested that it may be of interest to determine the frequency of subtelomeric rearrangements in individuals with learning difficulty and deficiency in social interaction, which are phenotypic features often considered to be of multifactorial causation.

Prontera et al. (2010) reported a pericentric inversion inv(18)(p11.32q22) and its recombinants in a 3-generation family, in which a mother and son carried the recombinant dup(18q)/del(18p). Both had short stature and facial dysmorphism, including slight asymmetry, prominent supraorbital ridges and glabella, mild palpebral ptosis, and bulbous tip of the nose. The son also displayed microretrognathia and low-set ears and had mild mental retardation and speech delay. Karyotype, subtelomeric FISH, and 0.8-Mb array CGH analyses detected no genomic differences between mother and son and refined the breakpoint of the duplication to 18q22.1-qter and the deletion to 18p11.32-pter. Prontera et al. (2010) stated that this was the first observation of familial transmission of a rec dup(18q), showing that this recombinant is associated with a mild phenotype with a variable clinical picture, and they noted that their findings support the hypothesis that a region critical for more severe phenotypes associated with duplications must be proximal to chromosome 18q22.1.