Craniofacioskeletal syndrome: an X-linked dominant disorder with early lethality in males

Am J Med Genet A. 2007 Oct 1;143A(19):2321-9. doi: 10.1002/ajmg.a.31928.


A syndrome with multisystem manifestations has been observed in three generations of a Caucasian family. The findings in seven females provide a composite clinical picture of microcephaly, short stature, small retroverted ears, full tip of the nose overhanging the columella, short philtrum, thin upper lip, soft tissue excrescences at the angle of the mouth, small mandible, small hands and feet with brachydactyly, finger V clinodactyly, flat feet, an excessive number of fingerprint arches, and mild impairment of cognitive function. Two males were more severely affected and died in the initial months of life. They showed intrauterine growth retardation, broad cranium with wide sutures and fontanelles, cardiac defects, small hands and feet with abnormal digital creases and small nails, and genital abnormalities. The affected males had low serum calcium in the neonatal period. Serum calcium, phosphorous, and parathormone levels in the females were normal. Radiographs showed cortical thickening of the long bones, underdevelopment of the frontal sinuses, narrow pelvis and hypoplasia of the middle phalanx of finger five. MRI of the brain showed slightly reduced brain volumes and an extra gyrus of the superior temporal region. X-inactivation studies showed near complete skewing in two affected females, but were not informative in three others. X-linkage as the mode of inheritance is proposed on the basis of different severity in males/females, complete skewing of X-inactivation in informative females, and a lod score (1.5) suggestive of linkage to markers in Xq26-q27.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Bone and Bones / abnormalities*
  • Cognition
  • Face / abnormalities*
  • Female
  • Genes, Dominant*
  • Genetic Diseases, X-Linked*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Pedigree
  • Skull / abnormalities*