Craniometaphyseal dysplasia, autosomal dominant (CMD)

(OMIM phenotype number #123000)

Craniometaphyseal dysplasia is a genetic syndrome involving cranial and tubular bone anomalies that commonly present at young age, in particular with otolaryngologic manifestations. The first sign is usually a thick bony wedge over the bridge of the nose and glabella. Cranial nerve impairment is also common. There are two forms, autosomal dominant and autosomal recessive, although other variants have been documented. The most common form is autosomal dominant, and the most cases involve familial clusters of Caucasian descent. The disease can be present in infancy, and there is a considerable variability of expression.

There are two major treatment regimens for this disease. The first is calcitonin therapy, which inhibits bone resorption primarily through osteoclast suppression and secondarily by impeding bone formation through feedback coupling to limit osteoblast activity. The other treatment is a low oral intake of calcium and the use of supplementation of calcitriol. A low calcium diet induces a hypocalcemic state stimulating osteoclast activation, and also calcitriol can stimulate the bone resorption. At last, surgical therapy can be necessary, such as craniofacial surgery.

Gene 

ANKH gene, 5p15.2 (OMIM gene/locus number #605145), encoding a putative pyrophosphate transporting membrane protein. Its primary known function is the transport of intracellular pyrophosphate into the extracellular matrix.

Phenotype 

Impaired vision, hearing loss, and facial nerve paralysis, metaphyseal flaring, hyperostosis and sclerosis of the cranial bones, sclerotic skull base, sclerotic calvarium, obliteration of sinuses, thick bony wedge over the bridge of the nose and glabella (first sign), bony paranasal bossing (often regresses with age), normal stature, macrocephaly, prognathism, hypertelorism, teeth malalignment, nasal obstruction leading to mouth breathing, widened metaphyses, 'Erlenmeyer flask' deformity of distal femur (childhood), club-shaped distal femur (adulthood).

Other resources

References

  1. Sheppard WM, Shprintzen RJ, Tatum SA, et al. Craniometaphyseal dysplasia: a case report and review of medical and surgical management. Int J Pediatr Otorhinolaryngol. 2003 Jun;67(6):687-93.
  2. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  3. http://www.omim.org