title: 22q11.2 duplication syndrome: two new familial cases with some overlapping features with DiGeorge/velocardiofacial syndromes.
abstract: Twenty-one patients, including our two cases, with variable clinical phenotype, ranging from mild learning disability to severe congenital malformations or overlapping features with DiGeorge/velocardiofacial syndromes (DG/VCFS), have been shown to have a chromosome duplication 22q11 of the region that is deleted in patients with DG/VCFS. The reported cases have been identified primarily by interphase FISH and could have escaped identification and been missed by routine cytogenetic analysis. Here we report on two inherited cases, referred to us, to rule out 22q11 microdeletion diagnosis of VCFS. The first patient was a 2-month-old girl, who presented with cleft palate, minor dysmorphic features including short palpebral fissures, widely spaced eyes, long fingers, and hearing loss. Her affected mother had mild mental retardation and learning disabilities. The second patient was a 7(1/2)-year-old boy with velopharyngeal insufficiency and mild developmental delay. He had a left preauricular tag, bifida uvula, bilateral fifth finger clinodactyly, and bilateral cryptorchidism. His facial features appeared mildly dysmorphic with hypertelorism, large nose, and micro/retrognathia. The affected father had mild mental retardation and had similar facial features. FISH analysis of interphase cells showed three TUPLE1-probe signals with two chromosome-specific identification probes in each cell. FISH analysis did not show the duplication on the initial testing of metaphase chromosomes. On review, band q11.2 was brighter on one chromosome 22 in some metaphase spreads. The paucity of reported cases of 22q11.2 microduplication likely reflects a combination of phenotypic diversity and the difficulty of diagnosis by FISH analysis on metaphase spreads. These findings illustrate the importance of scanning interphase nuclei when performing FISH analysis for any of the genomic disorders.
authors: Laboratoire de Cytogénétique, Hopital Saint-Antoine AP-HP, Paris, France. marie-france.portnoi@sat.ap-hop-paris.fr
authors: Marie-France
authors: MF
authors: Portnoï
authors: Fanny
authors: F
authors: Lebas
authors: Nicolas
authors: N
authors: Gruchy
authors: Azarnouche
authors: A
authors: Ardalan
authors: Valérie
authors: V
authors: Biran-Mucignat
authors: Valérie
authors: V
authors: Malan
authors: Lina
authors: L
authors: Finkel
authors: Gilles
authors: G
authors: Roger
authors: Sarah
authors: S
authors: Ducrocq
authors: Francis
authors: F
authors: Gold
authors: Jean-Louis
authors: JL
authors: Taillemite
authors: Sandrine
authors: S
authors: Marlin
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D002648:Child; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000235:genetics / Q000473:pathology; D003937:Diagnosis, Differential; D005145:Face / Q000002:abnormalities; D005192:Family Health; D005260:Female; D020440:Gene Duplication; D006330:Heart Defects, Congenital / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D008297:Male; D013577:Syndrome; D014681:Velopharyngeal Insufficiency / Q000473:pathology