Osteopathia Striata with Cranial Sclerosis

What is Osteopathia Striata with Cranial Sclerosis?

It is a rare genetic syndrome that belongs to a group of conditions known as skeletal dysplasia disorders. The symptoms of the syndrome mainly affect the bones, as well as the growth of an affected individual.

This syndrome is also known as:
Horan-Beighton syndrome OSCS

What gene changes cause Osteopathia Striata with Cranial Sclerosis?

The syndrome is caused by changes to the AMER1 gene. It is inherited in an X-linked dominant pattern.

With syndromes inherited in an X-linked dominant pattern, a mutation in just one of the copies of the gene, causes the syndrome. This can be in one of the female X chromosomes, and in the one X chromosomes males have. Males tend to have more severe symptoms than females.

What are the main symptoms of Osteopathia Striata with Cranial Sclerosis?

The main symptoms of the syndrome are congenital, making them present at birth.

Skeletal abnormalities are main features of the syndrome and they usually occur at the end of the long bones of the limbs. These abnormalities include sclerosis, which is a hardening of the bones of the face and skull. A very large head is common also.

In some individuals developmental delay is diagnosed, along with hearing loss and heart defects.

How does someone get tested for Osteopathia Striata with Cranial Sclerosis?

The initial testing for Osteopathia Striata with Cranial Sclerosis can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.

Medical information on Osteopathia Striata with Cranial Sclerosis

This is the combination of vertical striations of the metaphyses of the long bones (osteopathia striata), a large head with sclerosis, thickening of the skull vault and a variety of variable manifestations. The latter include cleft palate, mental retardation, and sensorineural deafness or other signs of cranial nerve compression including facial paralysis. Bar-Oz et al., (1996) reported an infant who most likely had the condition who had a duodenal web, PDA and a VSD. His mother was affected. Males can be more severely affected with Pierre-Robin anomaly and death in infancy (Winter et al., 1980; Bueno et al., 1998). The lack of convincing male to male transmission has raised the possibility of X-linked inheritance (Behninger and Rott, 2000). The condition is often lethal in males, especially (see below) when there is a WTX mutation in the 5' end of the gene (Perdu et al., 2011) , but this is not always the case. Smallness of the middle ear cavity, abnormal ossicular fixation and sclerosis of the mastoid cells occurred in the case reported by Magliulo et al., (2007). Viot et al., (2002) provide evidence for non-random X-inactivation in a mildly affected mother of a severely affected boy with the condition, again suggesting X-linked inheritance. In an X-linked family reported by Rott et al., (2003), 3 females had typical features, whereas a male had cranial sclerosis with frontal bossing, conductive deafness, cutaneous syndactyly of fingers 3 and 4, a cleft palate, hypertelorism, dysplastic, low-set ears, a small tongue, flat and broad nasal bridge, imperforate anus, malrotation of the gut, duplication of the distal phalanx of the 1st and 2nd digits of a hand, mental retardation, hypothyroidism and a pyloric stenosis. The cerebellar vermis was small. The patient reported by Ward et al., (2004), also had an anal stenosis, and the Pierre-Robin sequence. Males with a severe phenotype (omphalocele, duplicated phalanges, kidney malformations, cardiac defects, ventriculomegaly) differ from those with a mild phenotype (hearing loss, cleft palate and extensivr skeletal sclerosis) - Holman et al., (2011).
Konig et al., (1996) provde a good review of the literature up to 1996. The proband in the family they report had hydrocephalus requiring shunting but had normal development. 28% of patients had mild to moderate psychomotor or speech retardation.
It is difficult to asses the family reported by Pellegrino et al., (1997) where 4 males had osteosclerosis and brain anomalies including cerebral atrophy and internal hydrocephalus, as the radiographs shown do not show convincing striations. The mother and one sister were said to be more mildly affected, but again convincing radiographs of the long bones were not shown. It is possible that this family had a form of OPD2.
Nakamura et al., (1998) reported a 33 year old Japanese man with a relatively severe sclerosing bone dysplasia consisting of osteopathia striata and cranial sclerosis. There was significant metaphyseal undermodeling and also bone fragility. The radiographs showed features more severe than that normally seen in osteopathia striata-cranial sclerosis.
Jenkins et al., (2009) reported a female with severe OSCS and ascertained another 19 females and their affected relatives. They found a deletion at Xq11 in the proband and a mutation in WTX a gene that encodes a repressor of canonical WNT signalling. To date there has been no predisposition for developing tumours although Fujita et al., (2014) reported a case with hepatoblastoma. and there are references in this article to reportes of ovarian and clorectal cancer. Herman et al., (2013) reported a severe case with a whole WTX deletion. Holman et al., (2013) state that OSCS in a female that is not accounted for by a point mutation should prompt copy number analysis at this locus. They had a female with a contiguous WTX deletion and intellectual disability. A father who was mildly affected and thought to be mosaic for the mutation, had a severely affected daughter with a molecularly proven WTX mutation (Ciceri et al., 2013). They were initially thought to have osteopetrosis.
Costantini et al. (2017) described two patients with high bone mass. One female had a novel heterozygous frameshift mutation in the AMER1 gene. Clinical characteristics included developmental delay, rapidly increasing head circumference, choanal stenosis, laryngomalacia, subglottic stenosis, recurrent ear infections, and epilepsy. Dysmorphic features were triangular face, hypertelorism, micrognathia, short neck, flat nasal bridge, large open fontanelles, and two-parted xiphoid process. Brain MRI showed decreased white matter and wide lateral ventricles; X-rays demonstrated hyperostosis with longitudinal striations and uneven bone mineralization, underdeveloped sinuses, small jaw, open fontanels, mild scoliosis, and increased bone density.

* This information is courtesy of the L M D.
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