title: 15q overgrowth syndrome: a newly recognized phenotype associated with overgrowth, learning difficulties, characteristic facial appearance, renal anomalies and increased dosage of distal chromosome 15q.
abstract: Trisomy and tetrasomy of distal chromosome 15q have rarely been reported. Although most of the described patients have some learning difficulties and are overgrown, the phenotype associated with distal trisomy/tetrasomy 15q is uncertain due to the small numbers of reported cases and the common co-occurrence of additional chromosome deletions in many patients with trisomy 15q. We present five individuals with overgrowth, learning difficulties and increased dosage of distal 15q. Partial trisomy 15q was identified in four of these cases. Two were generated through recombination of a parental pericentric inversion and two were generated through malsegregation of a maternal balanced 14;15 reciprocal translocation. In all four cases the trisomy can be considered "pure" as the 14p and 15p monosomies will exert no phenotypic effect. Partial tetrasomy 15q, as the result of an analphoid supernumerary chromosome derived from an inverted duplication of distal 15q, was identified in the fifth patient. In addition to the overgrowth and learning difficulties, all five had a characteristic facial appearance and three had renal anomalies. The gestalt consists of a long, thin face with a prominent chin and nose. Renal anomalies included renal agenesis, horseshoe kidney, and hydronephrosis. We provide further support for a distinct "15q overgrowth syndrome" caused by either trisomy or tetrasomy resulting in increased dosage of distal 15q. In addition we propose that renal anomalies and a distinctive facial appearance be considered major features of this condition.
authors.affiliation: South West Thames Regional Genetics Service, St. Georges University of London, London, UK. katrina.tattonbrown@stgeorges.nhs.uk
authors.forename: Katrina
authors.initials: K
authors.lastname: Tatton-Brown
authors.forename: Daniela T
authors.initials: DT
authors.lastname: Pilz
authors.forename: Karen Helene
authors.initials: KH
authors.lastname: Orstavik
authors.forename: Michael
authors.initials: M
authors.lastname: Patton
authors.forename: John C K
authors.initials: JC
authors.lastname: Barber
authors.forename: Morag N
authors.initials: MN
authors.lastname: Collinson
authors.forename: Vivienne K
authors.initials: VK
authors.lastname: Maloney
authors.forename: Shuwen
authors.initials: S
authors.lastname: Huang
authors.forename: John A
authors.initials: JA
authors.lastname: Crolla
authors.forename: Karen
authors.initials: K
authors.lastname: Marks
authors.forename: Eli
authors.initials: E
authors.lastname: Ormerod
authors.forename: Peter
authors.initials: P
authors.lastname: Thompson
authors.forename: Zafar
authors.initials: Z
authors.lastname: Nawaz
authors.forename: Christa
authors.initials: C
authors.lastname: Lese-Martin
authors.forename: Susan
authors.initials: S
authors.lastname: Tomkins
authors.forename: Paula
authors.initials: P
authors.lastname: Waits
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
authors.forename: Meriel
authors.initials: M
authors.lastname: McEntagart
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000782:Aneuploidy; D049628:Body Size; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15; D005145:Face / Q000002:abnormalities; D005192:Family Health; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007674:Kidney Diseases; D007859:Learning Disabilities; D008297:Male; D010375:Pedigree; D010641:Phenotype; D013577:Syndrome