Osteopathia striata with cranial sclerosis (OSCS)

(OMIM phenotype number #300373)

Osteopathia striata is characterized by linear striations at the ends of long bones and in the iliac bones that can remain unchanged for years. The striations are parallel to the long axis of the bone and are typically described in areas of rapid growth such as the femur. In particular, the striations in the iliac bones can present a fan-shaped appearance due to the growth pattern of these bones. Sclerosis of the skull, cranial nerve palsies are also common. Although an autosomal dominant inheritance was suspected, it appears to be an X-linked dominant disease caused by mutations in the WTX (Wilms tumor on the X chromosome) gene, an inhibitor of WNT signaling. Interestingly, whereas Wnt is somatically inactivated in 30% of Wilms tumor patients, no increased incidence of cancer is found in the osteopathia striata or in any other sclerosing bone disorder related to activation of the Wnt pathway. The pathogenesis of this disorder is still unknown. This disease presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae. It is an X-linked dominant disease, but in hemizygous males it is usually associated with fetal or neonatal lethality. It is often accompanied by bilateral fibula aplasia.

Osteopathia striata with cranial sclerosis is a rare X-linked dominant sclerosing bone dysplasia characterized by longitudinal striations visible on radiographs of the metaphysis of the long bones, sclerosis of the craniofacial bones, macrocephaly, cleft palate and hearing loss. The phenotype is highly variable and vary from mild bone manifestations to multisystem organ involvement. Fewer than 100 cases have been reported up to now. OSCS follows an X-linked dominant pattern of inheritance, with frequent lethality in males.

Gene

AMER1 (WTX) gene, Xq11.2 (OMIM gene/locus number #300647)

Phenotype

Females: Long straight clavicole and striations visible on radiographs of the long bones, pelvis, and scapulae, sclerosis of the long bones and skull, sclerotic cranial base, sclerotic mastoids (31%), occipital bossing, thickened calvaria, bilateral fibula aplasia (always), increased trabecular thickness seen on iliac bone biopsy, joint contractures, trapezoidal shaped skull, thoracolumbar gibbus, scoliosis (23%), spina bifida occulta, absent or short fibulae, fifth finger clinodactyly, short stature and failure to thrive (in males), long and slender fingers, finger contractures, camptodactyly, duplicate phalanges spatulate, mild learning disabilities, macrocephaly, delayed closure of anterior fontanelle, large fontanelle, frontal bossing, widened sutures, bitemporal narrowing, micrognathia, hydrocephalus, headaches, speech delay (10%), transitional facial palsy (15%), hypotonia (in males), seizures (rare in males), mental retardation, mild-moderate (28%, usually in males), partial agenesis of corpus callosum (rare in males), hearing conductive loss, hypertelorism, cleft palate, ventricular septal defect, atrial septal defect, paranasal sinus hypoplasia, tracheomalacia, laryngeal web, broad and flat ribs, pectus excavatum, omphalocele (rare in males), multicystic kidney (rare in males), nemaline myopathy (in 1 reported male), intestinal malrotation (rare in males), anal stenosis (rare in males), anal atresia (rare in males), gastroesophageal reflux, fetal or neonatal lethality (male).
 

References

  1. Viot G, Lacombe D, David A, et al. Osteopathia striata cranial sclerosis: non-random X-inactivation suggestive of X-linked dominant inheritance.
  2. Am J Med Genet. 2002 Jan 1;107(1):1-4.
  3. Lazar CM, Braunstein EM, Econs MJ. Clinical vignette: osteopathia striata with cranial sclerosis. J Bone Miner Res. 1999 Jan;14(1):152-3.
  4. de Vernejoul MC, Kornak U. Heritable sclerosing bone disorders: presentation and new molecular mechanisms. Ann N Y Acad Sci. 2010 Mar;1192:269-77.
  5. Ihde LL, Forrester DM, Gottsegen CJ, et al. Sclerosing bone dysplasias: review and differentiation from other causes of osteosclerosis. Radiographics. 2011 Nov-Dec;31(7):1865-82.
  6. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Nov;26(11):2717-8.
  7. http://www.omim.org