Inverted duplication of 8p: Ten new patients and review of the literature

We evaluated 10 patients with an inverted tandem duplication of 8p. Inverted duplications of chromosome 8 have been reported infrequently, and no syndrome has been previously identified. All 8 patients on whom birth histories were available were hypotonic at birth, and had feeding difficulties in the neonatal period. All patients have significant developmental delay. Manifestations present in 5 or more patients were prominent forehead, high arched palate, large mouth with a thin upper lip, malformed and/or apparently lowset ears, broad nasal bridge, dental and skeletal abnormalities, and joint laxity or hyperextensibility. Variation in the phenotype may, in part, be explained by the different breakpoints. Recurrence risks of de novo rearrangements are probably very low, but for the recombinants the risk may be significant. The duplication appeared to be de novo in 6 patients (both parental karyotypes were normal); maternal karyotypes were normal in 2 patients, and both parents of 1 patient were not available. One propositus had a monocentric recombinant of a paracentric inv(8) (p12p23.3) carried by the mother, and is one of only 6 known cases of duplication associated with a balanced paracentric inversion in a parent. The carrier parent was the mother in 5 of those 6 cases. Each case involved a different chromosome, and each probably was created by an unusual meiotic recombination event. Inverted duplication 8p is one of the most common duplications observed in our laboratories, and ranks in frequency with the classical deletions, such as Wolf-Hirschhorn and cri-du-chat syndromes and duplication or secondary trisomy 15q1. Since 1/7 cases with complete parental karyotypes was associated with a familial rearrangement, parental karyotype studies should be considered in all cases of tandem duplication.