Severe osteopathia striata with cranial sclerosis in a female case with whole WTX gene deletion

Abstract

Osteopathia striata with cranial sclerosis (OSCS) is caused by truncating mutations or deletions in the X linked gene, WTX, and is characterized by sclerotic striations of the metaphyses and diaphyses of long bones, pelvis, and scapula, along with craniofacial hyperostosis. Females typically manifest with craniofacial dysmorphisms including macrocephaly, hypertelorism, depressed nasal bridge, and hypoplastic maxilla, often have cleft palate, and less often extra skeletal anomalies. Here we report on a sporadic female patient with OSCS born at 33 weeks, with coarse facies, an abnormal head shape, cleft palate, pyloric stenosis, a small VSD, and laryngotracheomalacia sufficiently severe to require tracheostomy placement. Characteristic radiologic findings were apparent on skeletal survey and cranial CT. At age 5, she showed mild delays in neurodevelopmental milestones. A deletion of WTX and the adjacent gene ASB12 was detected via MLPA and there was no skewing of the X-chromosome inactivation pattern (58:42). Neurodevelopmental delays can manifest in females with OSCS and deletions at the WTX locus, but deletion of the ASB12 gene in this case suggests it is unlikely to contribute to the pathogenesis of this complication. Implication of ASB12 in the patient's other unique features such as laryngotracheomalacia and pyloric stenosis is also unlikely. This case illustrates an early presentation of severe OSCS in a female without skewing of the X-chromosome inactivation pattern, emphasizing the variable expressivity of this disorder.

Prenatal diagnosis of osteopathia striata with cranial sclerosis

“…The diagnosis of OS‐CS in the mother and the fetus was performed in the postnatal period because the mother had a craniofacial dysmorphism with hearing loss and her radiographs showed cranial sclerosis and metaphyseal striations. Similar unspecific ultrasound findings were described by Herman et al ., Perdu et al, and Barbosa et al…”

A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma

“…X‐inactivation studies in 23 female patients with OSCS and WTX abnormalities, including the present patient, have shown random X‐inactivation patterns for all patients [Jenkins et al, ; Herman et al, ; Holman et al, ]. As three patients with a severe clinical phenotype showed random X‐inactivation [Herman et al, ; Jenkins et al, ], Herman et al [ suggested that X‐inactivation might not correlate with clinical severity. Or, marked skewing leading to a lack of wild‐type allele expression might cause lethality similar to affected male patients hemizygous for a null WTX allele.…”

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

“…However, one OSCS patient with a deletion of WTX did have pyloric stenosis and laryngotracheomalacia requiring tracheostomy placement. This is a rare finding infrequently reported in the literature [6]. Another spontaneous mutation (c.1108G > T) resulted in premature termination of translation, a truncated protein (E370X), and mosaicism in an OSCS patient [9].…”