INVERTED DUPLICATION OF 8P - 10 NEW PATIENTS AND REVIEW OF THE LITERATURE

We evaluated 10 patients with an inverted tandem duplication of 8p. In verted duplications of chromosome 8 have been reported infrequently, a nd no syndrome has been previously identified. All 8 patients on whom birth histories were available were hypotonic at birth, and had feedin g difficulties in the neonatal period. All patients have significant d evelopmental 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 low-set ears, broad nasal bridge, den tal and skeletal abnormalities, and joint laxity or hyperextensibility . Variation in the phenotype may, in part, be explained by the differe nt breakpoints. Recurrence risks of de novo rearrangements are probabl y very low, but for the recombinants the risk may be significant. The duplication appeared to be de novo in 6 patients (both parental karyot ypes were normal); maternal karyotypes were normal in 2 patients, and both parents of 1 patient were not available. One propositus had a mon ocentric recombinant of a paracentric inv(8) (p12p23.3) carried by the mother, and is one of only 6 known cases of duplication associated wi th a balanced paracentric inversion in a parent. The carrier parent wa s the mother in 5 of those 6 cases. Each case involved a different chr omosome, and each probably was created by an unusual meiotic recombina tion event. Inverted duplication 8p is one of the most common duplicat ions observed in our laboratories, and ranks in frequency with the cla ssical deletions, such as Wolf-Hirschhorn and cri-du-chat syndromes an d duplication or secondary trisomy 15q1. Since 1/7 cases with complete parental karyotypes was associated with a familial rearrangement, par ental karyotype studies should be considered in all cases of tandem du plication. (C) 1993 Wiley-Liss, Inc.