A male is described with familial duplication of the distal long arm of the X chromosome (Xq27.2-->qter) at the distal short arm (Xp22.3). The proband has features of the male Prada-Willi syndrome phenotype that have not previously been reported in other males with duplication of Xq27-->qter.

Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been previously described in seven patients, all of whom had a supernumerary marker chromosome (SMC) derived from distal 15q. These SMC contained no apparent centromeres (C-band/alpha-satellite negative), and belong to a novel class of SMC with neocentromeres. We present the oldest surviving patient with tetrasomy for distal 15q. The proposita was a 10-year-old girl with moderate to severe mental retardation, absent speech, hypotonia, minor facial anomalies, unusual digits, and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal, indicating a de novo origin for the SMC. FISH with a whole chromosome paint for chromosome 15 showed that the SMC was derived entirely from chromosome 15. However, C-banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and PML were all negative. FISH with the FES probe at 15q26 showed hybridization to both ends of the SMC. The marker was interpreted as an analphoid inverted duplication of 15q25-->qter containing a presumed neocentromere. Previous molecular studies suggested either a mitotic or paternal meiotic origin for these distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic markers showed that the analphoid SMC(15) in the proposita originated from a maternal meiotic error. The origins and mechanisms involved in formation of these distal 15q SMC appear to be more diverse than for the proximal pseudodicentic SMC(15).

Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been previously described in seven patients, all of whom had a supernumerary marker chromosome (SMC) derived from distal 15q. These SMC contained no apparent centromeres (C-band/alpha-satellite negative), and belong to a novel class of SMC with neocentromeres. We present the oldest surviving patient with tetrasomy for distal 15q. The proposita was a 10-year-old girl with moderate to severe mental retardation, absent speech, hypotonia, minor facial anomalies, unusual digits, and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal, indicating a de novo origin for the SMC. FISH with a whole chromosome paint for chromosome 15 showed that the SMC was derived entirely from chromosome 15. However, C-banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and PML were all negative. FISH with the FES probe at 15q26 showed hybridization to both ends of the SMC. The marker was interpreted as an analphoid inverted duplication of 15q25-->qter containing a presumed neocentromere. Previous molecular studies suggested either a mitotic or paternal meiotic origin for these distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic markers showed that the analphoid SMC(15) in the proposita originated from a maternal meiotic error. The origins and mechanisms involved in formation of these distal 15q SMC appear to be more diverse than for the proximal pseudodicentic SMC(15).

A 14-year-old boy was referred for a genetics evaluation after high-resolution chromosome analysis showed a small amount of extra material in the proximal long arm of chromosome 21. Five years prior, his karyotype analysis was interpreted as normal with a variant chromosome 21. The patient has short palpebral fissures, strabismus, flat antihelices of the ears, long thumbs with bilaterally absent interphalangeal creases, proximal bilateral 3/4 syndactyly, small testes, hypotonia, mental retardation, and speech problems. He has significant depression and behavioral problems including hyperactivity, aggression, and impulsivity. His 8-year-old brother has more severe behavioral disturbances and depression, but less significant mental retardation. A paternal aunt has mental retardation, is unusually docile, and appears similar to our patient. Chromosome analysis and fluorescence in situ hybridization (FISH) whole chromosome paint of chromosome 21 showed that the patient's father carries a "cryptic" balanced translocation, 46,XY, t(14;21)(q11.2;q11.2), as does the patient's paternal grandmother. Uniparental disomy studies using seven informative polymorphic nucleotide repeat markers from 14q and 21q confirmed biparental inheritance of the number 14 and 21 chromosomes for each brother, and indicate that they and the paternal aunt, all of whom inherited the der(14), are monosomic for proximal 21q and trisomic for proximal 14q. These karyotypes arose through an adjacent-2 segregation in the father on two occasions, and from the paternal grandmother on one occasion. This family is an example of recurrent malsegregation with translocations involving the acrocentrics.