Clinical implications of partial duplication Xp and random inactivation of chromosome X

VALERI, CLARA ; ARMANDO, ROMINA ; BAIALARDO, EDGARDO ; LAUDICINA, ALEJANDRO ; VALERI, DE BELLIS, RODOLFO; DEL REY, GRACIELA

Montevideo

Congreso; XXIII Annual Meeting of the Pediatrics Endocrinology Latinoamerican Society (SLEP); 2012

Sociedad Latinoamericana de Endocrinología Pediátrica

Pure duplications of the short arm of X chromosome are relatively rare. Males present mental retardation, multiple congenital malformations and short stature. Genetic imbalance in females with dup(Xp) is compensated  by preferential inactivation of their abnormal X-chromosome and are phenotypically normal. We report on a 8 years old girl with learning difficulties, few Turner Syndrome features and a mosaicism with partial duplication Xp and random X-inactivation.The physical examination showed :height: ( P10-25); weight: ( P75); head circumference (+1SDS). Growth velocity: 5.25cm/year. She had personal history of frequent atypical febrile seizures and primary enuresis. Features as wide palpebral fissures, big eyes, bulbous nose, rotated ears, short neck and bad dental occlusion and short hands were found. Abdominal, cranial, column ultrasound and echocardiography were normal.Chromosome analysis was performed in lymphocytes using high resolution, GTG and RHG banding. Karyotype: 45,X/46,X,dup(X)(p11.2p22.3). Parent´s karyotype: normal. FISH analysis with whole X-chromosome painting (wcpX), Xp11.2 and Xp22.3 Live probes, demonstrated tandem Xp duplication. Replication studies showed that the normal and duplicated X-chromosomes were randomly inactivated. Therefore, in this case there is X-monosomy, functional disomy Xp11-p22.1 in the cells with an active dup(X) and duplication of Xp22.3, resulting in a phenotypically abnormal female with intellectual disability.