Craniofacioskeletal Syndrome

Clinical Features

Stevenson et al. (2007) characterized an X-linked multisystem disorder with female expression and early postnatal lethality in males in a 3-generation family. The 7 affected females had microcephaly, short stature, short philtrum, thin upper lip, soft tissue excrescences at the angle of the mouth, small hands and feet with brachydactyly, fifth finger clinodactyly, and mild impairment of cognitive function. The 2 affected males were more severely affected and died in the first few months of life. Both males had intrauterine growth retardation, broad cranium with widened sutures and fontanels, cardiac defects, small hands and feet with abnormal creases, and genital abnormalities. Both also had episodes of hypocalcemia in the neonatal period. Radiographs of the females demonstrated absent or hypoplastic frontal sinuses, cortical thickening of the long bones and metacarpals, and tall, narrow ilia. Radiographs of the affected male infants were not available. MRIs of the females showed slightly reduced brain volumes and an extra gyrus of the superior temporal region. X-inactivation studies using the androgen receptor locus (313700) showed marked skewing (greater than 90:10) in 2 informative females.

Mapping

Using linkage analysis with 25 markers on the X chromosome, Stevenson et al. (2007) showed suggestive linkage to Xq26-q27 (lod score = 1.51).

Inheritance

Stevenson et al. (2007) proposed that this disorder is X-linked dominant or, alternatively, an X-linked syndrome that occurs predominantly in females.