Hypertelorism And Other Facial Dysmorphism, Brachydactyly, Genital Abnormalities, Mental Retardation, And Recurrent Inflammatory Episodes

Clinical Features

Spiegel et al. (2009) described 2 brothers, 15 years and 5 years old, and their 22-year-old male cousin, all born of unaffected consanguineous Muslim Arab parents, who displayed distinctive facial features consisting of hypertelorism, upslanting palpebral fissures, thick eyebrows, broad nasal bridge, long philtrum, wide mouth with upturned corners and thin upper lip, widow's peak, and simple ears with fleshy overfolded helices. Other features included mild to moderate mental retardation, short penis and cryptorchidism, and skeletal anomalies that included a combination of high pectus carinatum and low pectus excavatum, and small hands with short and relatively broad digits and fifth finger clinodactyly. Skeletal survey revealed short and broad metacarpals compatible with brachydactyly in the 2 older patients, whereas the younger brother's x-rays were interpreted as normal. In addition, the 2 older patients had recurrent inflammatory episodes: the cousin had recurrent episodes of inflammatory pericarditis with pericardial effusion, associated with fever and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP; 123260), since the age of 2 years. The 15-year-old brother had 4 documented episodes of limb cellulitis, 1 episode of pleural effusion, and 1 episode of perianal abscess; these episodes required intravenous antibiotics, with complete recovery. Immunologic and rheumatologic analyses in these 2 patients were normal.

Molecular Genetics

Exclusion Studies

In 2 brothers and their male cousin with facial dysmorphism, brachydactyly, genital abnormalities, mental retardation, and recurrent inflammatory episodes, Spiegel et al. (2009) performed whole-genome array CGH and detected no pathogenic copy number variations. Noting phenotypic overlap with autosomal recessive Robinow syndrome (268310) and familial Mediterranean fever (FMF; 249100), they analyzed the ROR2 (602337) and MEFV (608107) genes, but found no pathologic mutations.