Inherited Xq13.2-q21.31 duplication in a boy with recurrent seizures and pubertal gynecomastia: Clinical, chromosomal and aCGH characterization.
We report on a 16-year-old boy with a maternally inherited ~ 18.3 Mb Xq13.2-q21.31 duplication delimited by aCGH. As previously described in patients with similar duplications, his clinical features included intellectual disability, developmental delay, speech delay, generalized hypotonia, infantile feeding difficulties, self-injurious behavior, short stature and endocrine problems. As additional findings, he presented recurrent seizures and pubertal gynecomastia. His mother was phenotypically normal and had completely skewed inactivation of the duplicated X chromosome, as most female carriers of such duplications. Five previously reported patients with partial Xq duplications presented duplication breakpoints similar to those of our patient. One of them, a fetus with multiple congenital abnormalities, had the same cytogenetic duplication breakpoint. Three of the reported patients shared many features with our proband but the other had some clinical features of the Prader-Willi syndrome. It was suggested that ATRX overexpression could be involved in the major clinical features of patients with partial Xq duplications. We propose that this gene could also be involved with the obesity of the patient with the Prader-Willi-like phenotype. Additionally, we suggest that the PCDH11X gene could be a candidate for our patient's recurrent seizures. In males, the Xq13-q21 duplication should be considered in the differential diagnosis of Prader-Willi syndrome, as previously suggested, and neuromuscular diseases, particularly mitochondriopathies.
Setor de Citogenética/Laboratório Central do Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Natália D
ND
Linhares
Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Ambulatório de Erros Inatos do Metabolismo, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Eugênia R
ER
Valadares
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Silvia S
SS
da Costa
Ambulatório de Erros Inatos do Metabolismo, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Rodrigo R
RR
Arantes
Ambulatório de Erros Inatos do Metabolismo, Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Luiz Roberto
LR
de Oliveira
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Carla
C
Rosenberg
Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil.
Angela M
AM
Vianna-Morgante
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Marta
M
Svartman
5-BrdU, 5-bromodeoxyuridine; ATRX protein; ATRX, alpha thalassemia/mental retardation syndrome X-linked; CKT, creatinine kinase-phospho-total; CNV, copy number variation; CT, computed tomography; FISH, fluorescence in situ hybridization; HDAC8, histone deacetylase 8; JPX, JPX transcript; Mitochondrial disease; NMR, nuclear magnetic resonance; OFC, occipitofrontal circumference; PCDH11X protein; PCDH11X, protocadherin 11 X-linked; PCDH11Y, protocadherin 11 Y-linked; PCDH19, protocadherin 19; PCHD7, protocadherin 7; PWS, Prader–Willi syndrome; Prader-Willi syndrome; SLC16A2, solute carrier family 16, member 2; XIST, activator; Xq13-q21 duplication; aCGH, array comparative genomic hybridization