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

Abstract

Osteopathia striata with cranial sclerosis (OS-CS) or Horan-Beighton syndrome is a rare X-linked dominant inherited bone dysplasia, characterized by longitudinal striations of long bones and cranial sclerosis. Patients can be asymptomatic or present with typical facial dysmorphism, sensory defects, internal organs anomalies, growth and mental retardation, depending on the severity of the disease. WTX gene (Xq11) has been recently identified as the disease causing gene. Aim of this article is to present the case of a 6 year old girl initially evaluated for bilateral hearing loss. Patient’s head CT scan pointed out sclerosis of skull base and mastoid cells, and abnormal middle-ear ossification. Clinical examination of the patient and her mother were suspicious for OS-CS. The diagnosis was confirmed by X-rays examination showing typical longitudinal striation. Genetic analysis allowed the identification of maternally transmitted heterozygous nonsense c.1057C>T (p.R353X) WTX gene mutation. We also provide a systematic review of currently available knowledge about clinical, radiologic and genetic features typical of the OS-CS.

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

“…General information: Rare skeletal dysplasia with highly variable age at diagnosis and clinical presentation, ranging from asymptomatic to neonatal death. About 100 cases reported through 2012 …”

“…CNS: Occasional findings include ventriculomegaly, abnormal gyration pattern, and agenesis of the corpus callosum. Narrow cranial nerve canals and foramina cause nerve encroachment and palsies …”

“…About 100 cases reported through 2012. 299 Somatic findings: May occur in isolation or as part of a syndrome with heart defects, malrotation of the abdominal organs, omphalocele, partial callosal agenesis, and Pierre Robin sequence. Craniofacial dysmorphic features include macrocephaly, frontal and occipital bossing, mandible overgrowth with protuberance of the jaw and dental malocclusion, ocular hypertelorism, downslanting palpebral fissures, low-set broad nasal bridge, narrow high-arched or cleft palate, and low-set dysplastic ears.…”

“…Craniofacial dysmorphic features include macrocephaly, frontal and occipital bossing, mandible overgrowth with protuberance of the jaw and dental malocclusion, ocular hypertelorism, downslanting palpebral fissures, low-set broad nasal bridge, narrow high-arched or cleft palate, and low-set dysplastic ears. 299 Skeleton: Characterized by longitudinal striations of long bone diametaphyses (less frequently in the pelvis, vertebrae, and ribs) and diffuse osteosclerosis especially of the cranial vault and base. Rarely, thoracic and vertebral anomalies, digital flexion contractures, phalangeal duplication, syndactyly, short or absent fibula, and club feet.…”

Wnts’ fashion statement: from body stature to dysplasia

“…[66][67][68][69][70][71] The Wnt signaling pathways influence body stature and their deregulation leads to a plethora of pathological conditions expressed as different skeletal diseases ranging from epiphyseal dysplasia to spondyloepimetaphyseal dysplasia. Proper Wnt signaling activity is critical to normal bone development and homeostasis as either gain or loss of Wnt signaling activities adversely affects the skeleton resulting in skeletal dysplasias as summarized in Figure 1.…”