738 Molecular Characterization of DER (8) (QTERQ21.13: PTERP23.3) Dn In a Child Associating Psychomotor Retardation, Hydrocephalus and Facial Dysmorphism

Abstract

The deletion of the long arm of chromosome 18 causes a contiguous gene deletion syndrome with a highly variable phenotype, usually related to the extent of the deleted region. The most commonly reported clinical features include: mental disabilities, decreased growth, microcephaly and facial abnormalities. We report on a case with partial monosomy 18q22 derived from a maternal reciprocal translocation t(8; 18). The patient was 7 months old referred for genetic exploration of neurodevelopmental delay, craniofacial dysmorphism, post natal growth retardation, choanal atresia, club foot and congenital hip dislocation. Chromosome analysis from peripheral blood showed a 46, XY, der (18). Array CGH was performed and revealed a partial monosomy 18q21.33q22.31 of 15.3MB associated with partial trisomy 8q24.12q24.23 of 22.7MB region. These results were confirmed by FISH using telomeric 18q probe. Choanal atresia and skeletal malformation are in agreement with the monosomy 18q. Interestingly, the deletion includes GALR1 gene in 18q23 witch encodes galanine receptor. Galanine is a neuromodulator that stimulates growth hormone secretion. MBP, and adjacent genes, are implicated in myelination process and haploinsufficiency explains partially developmental delay. Otherwise, the haploinsufficiency of the 18q22.3-q23 gene region is suggested to be a critical region for the immunoglobuline A deficiency which is significantly associated to celiac disease. Our patient has not until now immunological desorders. The association deletion 18q22-GH deficiency and decreased myelinisation is now well estabilished. The real therapeutic impact of GH treatment is discussed.