Inherited polymalformative syndrome
characterized by typical facial features, enlarged viscera, and
skeletal anomalies. Short stature, cranial hyperostosis, hepatomegaly,
diabetes. Probably a variant of autosomal recessive type of
Approximately 30 cases have been reported.
Autosomal recessive inheritance with consanguinity being a risk factor.
The genetic defect has been mapped to 6q21-q22.
Craniofacial abnormalities include thickening of the cranial
bone with scaphocephaly (long, narrow cranium as a result of premature
closure of the sagittal suture) and frontal bossing, micrognathia with an arched
palate, and a beaked nose.
This autosomal recessive form is clinically more severe than the autosomal dominant
form (Craniodiaphyseal Dysplasia). Cranial hyperostosis frequently results in
cranial nerve compressions (blindness, deafness, facial palsy) and nasal obstruction.
Mild mental retardation is possible.
Hepatosplenomegaly is common, as is diabetes mellitus.
Abnormalities of the digits include brachydactyly and
clinodactyly, and the metacarpal bones may be abnormal. Patients are usually
small as a consequence of advanced bone age and early growth plate closure.
Fine hair and diffuse skin pigmentation often complete the clinical picture.
Potential for difficult airway if
micrognathia is present. Early closure of cranial suture lines may lead to
intracranial hypertension. Liver function studies (aspartate
aminotransferase, alanine aminotransferase, alkaline phosphatase,
bilirubin, international normalized ratio [INR], partial
thromboplastin time) and a complete blood count should be done;
splenic sequestration of platelets may be present. Perioperative management of
diabetes mellitus depends on the timing and duration of surgery; involvement
of an endocrinologist may be helpful. Nasal breathing as well as nasal passage of tubes
(nasogastric or endotracheal) may be impossible.
Avoid medications and anesthesia techniques known to potentially
increase intracranial pressure in patients with craniosynostosis.
Craniodiaphyseal Dysplasia: Progressive hyperostosis leading to
lifelong thickening of craniofacial bones and widening of the metaphyses of
long bones. Autosomal dominant.
Elcioglu N, Hall CM: Temporal aspects in craniometaphyseal dysplasia:
Autosomal recessive type. Am J Med Genet
Iughetti P, Alanso LG, Wilcox W, et al: Mapping of the autosomal recessive (AR)
craniometaphyseal dysplasia locus to chromosome region 6q21-22 and confirmation
of genetic heterogeneity for mild AR spondylocostal dysplasia. Am
J Med Genet