Osteopathia striata cranial sclerosis: Non‐random X‐inactivation suggestive of X‐linked dominant inheritance

Abstract

Osteopathia striata with cranial sclerosis (OS-CS) is a rare syndrome comprising macrocephaly, minor anomalies, conductive hearing loss, and mild mental retardation. The diagnosis is based on radiological findings, including cranial sclerosis and longitudinal striations of metaphyses of long bones. Here we report on 10 new cases of OS-CS, including two sporadic cases and three families, with an excess of affected females (9F/1M). Phenotypic variability was observed in our patients as well as several unusual findings. Hirschsprung disease, Pierre Robin sequence, coronal craniostenosis, and laryngotracheomalacia were associated with a poor prognosis. The X-inactivation pattern of peripheral blood lymphocytes in a mildly affected mother and her severely affected boy demonstrated a non-random X-inactivation in the mother. This finding, in combination with a sex ratio in favor of females and an increased morbidity and mortality in males, is highly suggestive of X-linked dominant inheritance.

WTX R353X mutation in a family with osteopathia striata and cranial sclerosis (OS-CS): case report and literature review of the disease clinical, genetic and radiological features

“…Facial dysmorphisms include macrocephaly (43%) [2,11-17,19,20,27-32,34,36-39], frontal and occipital bossing (32%) [2,11-15,17,19-21,30-33,36], mandible overgrowth with protuberance of the jaw and dental malocclusion (12%) [2,11,14,23] (giving a leonine appearance), ocular hypertelorism [6,8,10,14,19,20,23,27,29-31,38-40], down-slanting palpebral fissures [19,28,31], low set broad nasal bridge (29%) [1,2,6,8,12,14,15,17,18,20,23,30-32,37,38,41,42], narrow high-arched or cleft palate (Pierre Robin’s triad) (12%) [2,6,8,14-16,19,21,30,31,35] and low set dysplastic ears (9%) [6,12,19,20,29-31,33,39,42]. …”

“…Patients can also present thoracic and vertebral anomalies (2%) [8,13,14,19-21,28-32,35,42], digital flection contractures, phalangeal duplication, syndactyly, short or absent fibula, club feet (3%) [8,10,14,16,17,20,28-31,35,36,38,40]. …”

Osteopathia striata with cranial sclerosis (OSCS): review of the literature and case report demonstrating challenges of spinal fusion after trauma

“…The inheritance pattern was initially thought to be autosomal dominant, but recent evidence suggests it to be X-linked dominant [14]. One study suggested that mutations involving the WTX (FAM123B) gene on the X-chromosome are responsible for the disease by enhancing WNT signaling [8].…”

Temporal Bone CT Findings in a Male Patient with Osteopathia Striata and Cranial Sclerosis

“…The inheritance of this variant is referred as autosomal dominant. However, the clinical pattern of partial involvement, as well as the reported family observations pleads for X-linked inheritance with mild striated bone affections to carrier women and severe syndromic morbidity and high mortality to the males [1,17]. Descriptions of biochemical findings and biopsy changes in patients having osteopathia striata with cranial sclerosis are scarce [6,12,15].…”