Inherited maternal duplication Xq25-qter at Xp22.3 in a boy with growth retardation and severely affected phenotype.

GRACIELA DEL REY; ANA TANGARI; ADRIANA BOYWITT; RODOLFO DE BELLIS.

Viña del Mar, Chile

Congreso; XVIII Annual Meeting of the Sociedad Latinoamericana de Endocrinología Pediátrica; 2006

Sociedad Latinoamericana de Endocrinología Pediátrica

Duplication of the long arm of the X chromosome (dup Xq) with deletion of the short arm (del Xp) are infrequent and, the few males reported all have an abnormal phenotype with multiple congenital anomalies including developmental delay/mental retardation and short stature. The most females who carry the same abnormal X chromosome have normal phenotype because they are protected from genetic imbalance through preferential inactivation of the duplicated X chromosome. In spite this, a few cases reported had mild Turner phenotype. We present a nine-month-old boy with a maternally transmitted Xp+ chromosome which was associated with an abnormal phenotype, severe pre and posnatal growth retardation, profound developmental delay and hypotonia. He was the firt and only child from nonconsaguineous parents after a pregnancy of 27 weaks because fetal distress. Birth weigh was 1200g. At the examination: Height: 55cm, OFC: 41cm ( all below the 3rd centile) and dysmorphic facial features. Scholiosis. He developed feeding difficulties. On frequently occasions he was admitted to hospital by pneumonia. His mother´s height: 152 cm with short 4th and 5th metacarpian of the left hand, without mentally impaired. By cytogenetics analysis with GTG and R banding in standard methods and high resolution was observed a derivative X chromosome which additional material of Xq on the distal short arm. The patient´s mother showed the same abnormal X chromosome. FISH with an X chromosome paint probe (wcpX) hybridized to the entire short arm of the abnormal X, confirming the additional material was X chromosome derived. A probe for Xp22.3 (Kal probe) showed no deletion in the abnormal X chromosome in either the patient and his mother, indicating that the rearrangement occurred distal to this locus. These data permitted interpretation of the abnormality as dup(X)(qter-q25::p22.33-qter) without evidence of mosaicism. Replication studies were performed on lymphocytes from the patien´s mother by incorporation of bromodeoxiuridine (BrdU) during the last six hours of culture. The abnormal X chromosome was shown to be predominantly inactive in 80 % of the metaphases witih complete and partial late replicating. We conclude that the functional disomy of Xq was responsible of phenotypically abnormal boy. In his mother the preferential inactivation of the abnormal X chromosome in the mayority of cells express a mosaic with monosomy/trisomy of the duplicated Xq region compatible with fertility.