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Submicroscopic recurrent 16p11.2 rearrangements are associated with several neurodevelopmental disorders, including autism, mental retardation, and schizophrenia. The common 16p11.2 region includes 24 known genes, of which 22 are expressed in the developing human fetal nervous system. As yet, the mechanisms leading to neurodevelopmental abnormalities and the broader phenotypes associated with deletion or duplication of 16p11.2 have not been clarified. Here we report a child with spastic quadriparesis, refractory infantile seizures, severe global developmental delay, hypotonia, and microcephaly, and a de novo 598 kb 16p11.2 microduplication. Family history is negative for any of these features in parents and immediate family members. Sequencing analyses showed no mutations in DOC2A, QPRT, and SEZ6L2, genes within the duplicated 16p11.2 region that have been implicated in neuronal function andor seizure related phenotypes. The childs clinical course is consistent with a rare seizure disorder called malignant migrating partial seizure disorder of infancy, raising the possibility that duplication or disruption of genes in the 16p11.2 interval may contribute to this severe disorder. © 2010 WileyLiss, Inc.

We report on a 26monthold boy with developmental delay and multiple congenital anomalies, including many features suggestive of either branchiootorenal syndrome BOR or oculoauriculovertebral spectrum OAVS. Chromosomal microarray analysis CMA initially revealed a copynumber gain with a single BAC clone RP1179M1 mapping to 14q23.1. FISH analysis showed that the third copy of this genomic region was inserted into the long arm of one chromosome 13. The same pattern was also seen in the chromosomes of the father, who has mental retardation, short stature, hypernasal speech, and minor craniofacial anomalies, including tall forehead, and crowded dentition. Subsequent whole genome oligonucleotide microarray analysis revealed an ∼11.79 Mb duplication of chromosome 14q22.3–q23.3 and a loss of an ∼4.38 Mb sequence in 13q21.31–q21.32 in both the propositus and his father and FISH supported the apparent association of the two events. Chromosome 14q22.3–q23.3 contains 51 genes, including SIX1, SIX6, and OTX2. A locus for branchiootic syndrome BOS has been mapped to 14q21.3–q24.3, and designated as branchiootic syndrome 3 BOS3. Interestingly, mutations in SIX1have been reported in patients with BORBOS3. We propose that the increased dosage of SIX1, SIX6, or OTX2may be responsible for the BOR and OAVSlike features in this family. © 2008 WileyLiss, Inc.

Ring chromosomes are thought to be the result of breakage in both arms of a chromosome, with fusion of the points of fracture and loss of the distal fragments. Another mechanism of ring formation is believed to be the simple fusion of chromosome ends with preservation of telomeric and subtelomeric sequences. Ring chromosome 13 was first described in 1968 and its incidence estimated at 1 in 58,000 live births. Severe phenotypes associated with large deletions of 13q have been described as “ring chromosome 13 syndrome.” Features of the “ring chromosome 13 syndrome” include mental retardation (often severe), growth retardation, microcephaly, facial dysmorphism, and hand, foot or toe abnormalities. We report on a case of a mother and daughter with r(13) and mild phenotypes. Our patient, IA, had chromosome analysis performed at about 4½ years of age due to some developmental delay. This revealed 46,XX, r(13)(p13q34) karyotype with no loss of any chromosomal band. Her mother, EA, was subsequently found to have the same ring 13. IA's maternal grandmother had a normal karyotype while her maternal grandfather was unavailable for testing. Fluorescence in situ hybridization (FISH) analysis showed loss of a specific subtelomeric 13q region in r(13) in the mother. Clinically, IA had macular hyperpigmentation on the chin and mild delay in speech and fine motor skills. EA, 22 years of age, had mild short stature and borderline mental retardation. To our knowledge, this is the first report of a case of familial transmission of r(13). We compare phenotypes of our cases with those from other reported cases of r(13) and discuss the possible mechanism of formation of this ring chromosome. © 2004 Wiley‐Liss, Inc.