Síndrome de Prader-Willi por disomía uniparentalmaterna y cariotipomos 47,XX,+mar/46,XX.

Abstract

Prader-Willi syndrome (PWS) is a neurogenetic disorder that results from different abnormalities involving chromosome 15, which could have either a (q11-q13) paternal microdeletion, maternal uniparental disomy (UPD) or a defect of the imprinting centre. Recently, it has been observed that the risk of UPD for any chromosome is increased when a supernumerary marker chromosome (SMC) is present. In fact, four mechanisms have been proposed to explain UPD in individuals carrying a SMC: 1) Functional trisomy rescue: In a trisomic zygote one of the three chromosomes undergoes a rearrangement to form a SMC, thereby reducing the chromosome complement to two. 2) Postzygotic reduplication: In a zygote which has inherited a SMC in place of the normal corresponding chromosome, a duplication of the normal chromosome homologue occurs to “rescue” the cell from aneuploidy. 3) Postfertilisation error: a postzygotic formation by either nondisjunction in early mitosis and subsequent reduction of the monosomic chromosome homologue or vice versa. 4) Complementation: fertilisation of a disomic gamete by a gamete having a SMC formed before, or during meiosis. Here we present a malformed newborn girl who presented with arched palate, amimic facies, congenital hips laxity, right talus valgus, marked hypotonia, breathing difficulties and hyaline membrane requiring antibiotics treatment. Cytogenetic analysis on blood culture showed two cellular lines, one normal (93.2% of the cells) and the other with a SMC present in 6.8% of the cells (47, XX, +mar/46,XX). As the clinical features of the patient suggested the PWS, Fluorescence In Situ Hybridization (FISH) analysis with the specific 15(q11-q13) region probe was performed, which gave normal results. However, the FISH and microsatellites analyses demonstrated that the SMC was derived from a chromosome 15, and the presence of maternal UPD for chromosome 15. As far as we know, this is the seventh reported patient with PWS, generated by maternal UPD of the chromosomes 15 due to the presence of a SMC (15). Therefore, we believe that is important to consider the increase risk of UPD in patients with a SMC, which is independent of the SMC origin and size, and the high implication for prenatal diagnosis.