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

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.

The male phenotype in osteopathia striata congenita with cranial sclerosis.

Osteopathia striata with cranial sclerosis (OSCS) is an X-linked disease caused by truncating mutations in WTX. Females exhibit sclerotic striations on the long bones, cranial sclerosis, and craniofacial dysmorphism. Males with OSCS have significant skeletal sclerosis, do not have striations but do display a more severe phenotype commonly associated with gross structural malformations, patterning defects, and significant pre- and postnatal lethality. The recent description of mutations in WTX underlying OSCS has led to the identification of a milder, survivable phenotype in males. Individuals with this presentation can have, in addition to skeletal sclerosis, Hirschsprung disease, joint contractures, cardiomyopathy, and neuromuscular anomalies. A diagnosis of OSCS should be considered in males with macrocephaly, skeletal sclerosis that is most marked in the cranium and the absence of metaphyseal striations. The observation of striations in males may be indicative of a WTX mutation in a mosaic state supporting the contention that this sign in females is indicative of the differential lyonization of cells in the osteoblastic lineage.

WTX mutations can occur both early and late in the pathogenesis of Wilms tumour.

BACKGROUND: Somatic mutations in the X-linked tumour suppressor gene WTX have been observed in 6- 30% of sporadic cases of Wilms tumour. Germline mutations in the same gene cause the sclerosing skeletal dysplasia, osteopathia striata congenita with cranial sclerosis (OSCS). No evidence points towards a susceptibility to the development of tumours in individuals with OSCS, suggesting that there are unrecognised additional determinants that influence the phenotypic outcome associated with germline mutations in WTX. One explanation may be that a somatic mutation in WTX may need to occur late in tumour development to contribute to tumourigenesis. METHODS: Here a panel of four sporadic Wilms tumours with associated nephrogenic rest tissue and characterised WTX and CTNNB1 mutations is studied to ascertain the temporal sequence of acquisition of these mutations. Additionally, a family with OSCS is described segregating a germline mutation in WTX and manifesting a lethal phenotype in males. One male from this family had bilateral multifocal nephrogenic rests at autopsy. RESULTS: In one of the four tumours the WTX mutation was present in both tumour and rest tissue indicating it had arisen early in tumour development. In the remaining three tumours, the WTX mutation was present in the tumour only indicating late acquisition of these mutations. CONCLUSIONS: These data indicate that WTX mutations can arise both early and late in Wilms tumour development. WTX mutations may predispose to nephrogenic rest development rather than Wilms tumour per se.

Design and implementation of a pilot student wellness program at a school of pharmacy.

BACKGROUND AND PURPOSE: In response to concerns about student stress and well-being, a volunteer wellness task force was formed to promote a culture of wellness at the school of pharmacy (SOP). The purpose of this paper is to describe the development and implementation of this pilot wellness program. EDUCATIONAL ACTIVITY AND SETTING: A task force was formed to design and implement a pilot wellness program for pharmacy students. Interventions included: orientation to wellness program, sessions on nutrition and mindfulness, in-class brain breaks, and promotion of on-campus resources. Student wellness was assessed at baseline with a questionnaire including sociodemographic data, perceived stress levels using the Perceived Stress Scale (PSS-10), wellness practices, and use of wellness resources. Program feedback was obtained using a post-questionnaire to identify student perceptions and preferences for wellness activities. FINDINGS: Pharmacy year one through three students (n = 166) were included in the pilot wellness program, with 92.2% and 88.8% completing the baseline and post-questionnaires, respectively. There were notable changes in wellness practices compared to baseline including an increase in weekly exercise and sleeping >4 hours a night. There was greatest use of and satisfaction with 5- to 10-min in-class wellness breaks. The mean student PSS-10 baseline score was 20.14 while the post-implementation mean score was 19.62. SUMMARY: This study demonstrates the potential for implementing a faculty-driven wellness program despite limited resources. The design, implementation, and lessons learned from this pilot program may serve as a practical framework for institutions seeking to promote student wellness.

Acute Low-Dose Hydralazine-Induced Lupus Pneumonitis.

A 35-year-old female was started on hydralazine 10 mg orally three times a day for treatment of postpartum hypertension. Three months later, after multiple unsuccessful courses of prednisone and antibiotics for presumed pneumonia and asthma exacerbations, her respiratory symptoms progressed in severity and she developed resting hypoxia. Previous diagnostic work-up included spirometry with a restrictive pattern, chest CT showing bilateral basilar consolidation, negative BAL, and nonspecific findings on lung biopsy of mild inflammatory cells. Review of systems was positive for arthralgia, lymphadenopathy, paresthesia, and fatigue that began four weeks after starting hydralazine. A clinical diagnosis of hydralazine-induced lupus (HIL) with pneumonitis was made. Antihistone antibodies were positive supporting a diagnosis of HIL. Management included cessation of hydralazine and a prolonged steroid taper. Within days, patient began improving symptomatically. Six weeks later, CT chest showed complete resolution of infiltrates. Genetic testing revealed she was heterozygous for N-acetyltransferase 2 (intermediate acetylator). Drug-induced lupus should be considered in patients with lupus-like symptoms taking medications with a known association. While the majority of HIL cases occur with high doses and prolonged treatment, cases of low-dose HIL have been reported in patients who are slow acetylators.