Subtelomeric deletions of chromosome 6p: Molecular and cytogenetic characterization of three new cases with phenotypic overlap with Ritscher-Schinzel (3C) syndrome

• Published in: American journal of medical genetics. Part A Vol. 134A; no. 1; pp. 3 - 11
• Main Authors: DeScipio, Cheryl, Schneider, Lori, Young, Terri L., Wasserman, Nora, Yaeger, Dinah, Lu, Fengmin, Wheeler, Patricia G., Williams, Marc S., Bason, Lynn, Jukofsky, Lori, Menon, Ammini, Geschwindt, Ryan, Chudley, Albert E., Saraiva, Jorge, Schinzel, Albert A. G. L., Guichet, Agnes, Dobyns, William E., Toutain, Annick, Spinner, Nancy B., Krantz, Ian D.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2005
• Subjects: 3C syndrome; 6p25 subtelomeric deletion; Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; anterior chamber; Cerebellum - abnormalities; Child; Child, Preschool; Chromosome Banding; Chromosome Deletion; Chromosomes, Human, Pair 16 - genetics; Chromosomes, Human, Pair 6 - genetics; congenital heart defect; Craniofacial Abnormalities - pathology; Dandy-Walker malformation; Diagnosis, Differential; Family Health; Fatal Outcome; Female; Fetal Death; FOXC1; FOXF2; FOXQ1; Heart Defects, Congenital - pathology; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Male; Phenotype; Ritscher-Schinzel syndrome; Syndrome; Telomere - genetics; Translocation, Genetic
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.30573

We have identified six children in three families with subtelomeric deletions of 6p25 and a recognizable phenotype consisting of ptosis, posterior embryotoxon, optic nerve abnormalities, mild glaucoma, Dandy–Walker malformation, hydrocephalus, atrial septal defect, patent ductus arteriosus, and mild mental retardation. There is considerable clinical overlap between these children and individuals with the Ritscher–Schinzel (or cranio–cerebello–cardiac (3C)) syndrome (OMIM #220210). Clinical features of 3C syndrome include craniofacial anomalies (macrocephaly, prominent forehead and occiput, foramina parietalia, hypertelorism, down‐slanting palpebral fissures, ocular colobomas, depressed nasal bridge, narrow or cleft palate, and low‐set ears), cerebellar malformations (variable manifestations of a Dandy–Walker malformation with moderate mental retardation), and cardiac defects (primarily septal defects). Since the original report, over 25 patients with 3C syndrome have been reported. Recessive inheritance has been postulated based on recurrence in siblings born to unaffected parents and parental consanguinity in two familial cases [Ritscher et al. (1987); Am J Med Genet 26:481–491; Marles et al. (1995); Am J Med Genet 56:343–350; Orstavik et al. (1998); Am J Med Genet 75:300–303]. Molecular and cytogenetic mapping of the 6p deletions in these three families with subtelomeric deletions of chromosome 6p have defined a 1.3 Mb minimally deleted critical region. To determine if 6p deletions are common in 3C syndrome, we analyzed seven unrelated individuals with 3C syndrome for deletions of this region. Three forkhead genes (FOXF1 and FOXQ1 from within the critical region, and FOXC1 proximal to this region) were evaluated as potential candidate disease genes for this disorder. No deletions or disease‐causing mutations were identified. © 2005 Wiley‐Liss, Inc.