Siblings with phenotypic overlap with Toriello-Carey syndrome and complex cytogenetic imbalances including 3q29 microduplication and 6p25 microdeletion: Review of the literature and additional evidence for genetic heterogeneity

• Published in: American journal of medical genetics. Part A 2010-12, Vol.152A (12), p.3068-3073
• Main Authors: McGoey, Robin, Varma, Aditi, Lacassie, Yves
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; aCGH; Adolescent; Agenesis of Corpus Callosum; Biological and medical sciences; Child; Chromosome aberrations; Chromosome Deletion; Chromosome Duplication; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 6; Classical genetics, quantitative genetics, hybrids; Corpus Callosum - pathology; corpus callosum hypoplasia; Craniofacial Abnormalities - complications; Craniofacial Abnormalities - genetics; cytogenetic imbalance; Fathers; Female; FISH; Fundamental and applied biological sciences. Psychology; Genetic Heterogeneity; Genetics of eukaryotes. Biological and molecular evolution; Heart Defects, Congenital - complications; Heart Defects, Congenital - genetics; Human; Humans; Intellectual Disability - etiology; Intellectual Disability - genetics; Intellectual Disability - pathology; Male; Medical genetics; Medical sciences; microdeletion 6p25; microduplication 3q29; Phenotype; reciprocal translocation; Siblings; Syndrome; Toriello-Carey syndrome; Translocation, Genetic
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.33721

Toriello–Carey syndrome (TCS) is a multiple congenital anomaly syndrome of unknown etiopathogenesis with characteristic findings including corpus callosum defects, minor facial dysmorphisms, mental retardation, postnatal growth delays, cardiac defects, limb anomalies and genitourinary defects in affected males. This report describes two siblings with features of the TCS in whom array comparative genomic hybridization detected both a 3q29 microduplication as well as a 6p25 microdeletion due to an unbalanced translocation inherited from the father. Though neither microscopic copy number imbalance has been previously attributed to the TCS, this report supports the assertion that roughly 25% of patients with presumed TCS by phenotype may harbor underlying cytogenetic aberrations. Further, this report maintains that, until the specific causative gene is identified, a diagnosis of TCS be reserved for those patients who have not only the salient clinical features but also normal genetic studies that should include microarray. © 2010 Wiley‐Liss, Inc.