Chromosome Xq27.3-Q28 Duplication Syndrome

A number sign (#) is used with this entry because this disorder is caused by copy number increase of a 5.1-Mb region of chromosome Xq27.3-q28 encompassing at least 28 genes, including FMR1 (309550).

Description

Chromosome Xq27.3-q28 duplication syndrome is an X-linked recessive neurodevelopmental disorder characterized by mild mental retardation, mild facial dysmorphism, short stature, and primary testicular failure manifest as high-pitched voice, sparse body hair, abdominal obesity, and small testes. Female carriers may have short stature and premature ovarian failure (summary by Rio et al., 2010).

Clinical Features

Rio et al. (2010) reported a French family in which 3 adult males had syndromic mild mental retardation. All had low birth weight, reflecting intrauterine growth retardation, and delayed psychomotor development. One had neonatal hypotonia and failure to thrive. The patients all attended school and showed learning difficulties, but learned to read and write. Two were unable to work, but 1 worked in a factory. Dysmorphic features included deep-set eyes, bulbous nasal tip, thin lips, and small hands and feet. All had cryptorchidism and primary hypogonadism, manifest by high-pitched voice, sparse body hair, abdominal obesity, gynecomastia, and small testes. The patients had short stature, which was also found in 3 obligate female carriers. Laboratory studies showed increased gonadotropins and low testosterone; brain MRI of 1 patient was normal. Three obligate female carriers had normal cognitive findings, but short stature and early menopause. X-inactivation studies showed completely skewed inactivation in 3 of 5 female carriers.

Inheritance

The transmission pattern of the chromosome Xq27.3-q28 duplication syndrome in the family reported by Rio et al. (2010) was consistent with X-linked recessive inheritance.

Cytogenetics

Using array CGH in a French family with X-linked syndromic mental retardation, Rio et al. (2010) identified a 5.1-Mb duplication of chromosome Xq27.3-q28 encompassing at least 28 genes. The region included the FMR1 (309550), FMR2 (AFF2; 300806), IDS (300823), and MTM1 (300415) genes, but not MECP2 (300005). Rio et al. (2010) noted that females with FMR1 premutations have an increased risk of premature ovarian failure, which was observed in female carriers in this family.