Multiple congenital anomalies, brain hypomyelination, and ocular albinism in a female with dup(X)(pter→q24::q21.32→qter) and random X inactivation

We report on an 18-month-old girl with multiple congenital anomalies (prominence of the metopic suture, fine hair, club foot, absence of the 12th rib, brachydactyly) and severe mental retardation. The funduscopic examination showed diffuse retinal hypopigmentation. Brain magnetic resonance image (MRI) showed signs of diffuse hypomyelination. On cytogenetic and molecular evidence, the karyotype was 46,X,dirdup(X) (pter→q24::q21.32→qter). The duplication of the PLP gene, involved in Pelizaeus-Merzbacher disease, was confirmed by fluorescent in situ hybridization (FISH). Both cytogenetic and molecular studies on the X chromosome inactivation status indicated a random pattern in lymphocytes and fibroblasts. This patient appears to be the first case of a female bearing a large duplication of Xq with a random X inactivation. The phenotype of this patient is compared to that of previously reported cases with Xq duplication.