Copy Number Gain at Xq28 in a Child with Global Developmental Delay Associated with a Variant Form of Hoyeraal-Hreidarsson Syndrome.

We report the case of a child from Central Brazil with global developmental delay (GDD), syndromic features, and absence of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, with a rearrangement at Xq28 harboring the DKC1 gene. GTC-banding revealed a male karyotype (46,XY) with no visible numerical or structural alterations. Chromosomal microarray analysis (CMA) showed a 0.36-Mb gain at Xq28 of maternal origin, encompassing 22 genes, including DKC1. Rearrangements and mutations involving this gene have been associated with dyskeratosis congenita, X-linked (OMIM 305000) and Hoyeraal-Hreidarsson syndrome. CMA was a powerful and efficient approach to identify a gain at Xq28 harboring the DKC1 gene in our patient with GDD syndromic features and no cutaneous alterations, suggesting that this variant is associated with the Hoyeraal-Hreidarsson syndrome.

Molecular Characterization of Koolen De Vries Syndrome in Two Girls with Idiopathic Intellectual Disability from Central Brazil.

Koolen de Vries syndrome (KDVS; MIM 610443) is a genomic disorder caused by a recurrent microdeletion derived from nonallelic homologous recombination mediated by flanking segmental duplications. Clinical manifestations of this syndrome are characterized by intellectual disability, hypotonia, a friendly behavior, distinctive facial features, and epilepsy. Herein, we report a case of 2 girls who revealed global developmental delay, mild facial dysmorphisms, friendly behavior, and epileptic seizure with a de novo 17q21.31 microdeletion detected by chromosomal microarray analysis (CMA). Conventional cytogenetics analysis by GTG-banding showed a female karyotype 46,XX for both girls. CMA revealed a microdeletion spanning approximately 500 kb in 17q21.31 in both girls, encompassing the following genes: CRHR1, MGC57346, CRHR1-IT1, MAPT-AS1, SPPL2C, MAPT, MAPT-IT1, STH, and KANSL1. Haploinsufficiency of one or more of these genes within the deleted region is the most probable cause of the probands' phenotype and is responsible for the phenotype seen in KDVS. CMA is a powerful diagnostic tool and an effective method to identify the de novo 17q21.31 microdeletion associated with KDVS in our probands.