Johanson-Blizzard syndrome caused by novel UBR1 mutation in four Saudi patients.

Johanson-Blizzard syndrome (JBS) is a rare genetic disorder caused by Ubiquitin Protein Ligase E3 Component N-Recognin1 (UBR1) gene mutations. It is characterized by exocrine pancreatic insufficiency, craniofacial deformities, sensorineural hearing loss, and a broad variety of intellectual disabilities. The aim of our study is to report four pediatric cases (three of which are siblings, and the fourth patient is unrelated) that presented some features of JBS. The cases have been confirmed by genetic testing to have mutations in the UBR1 gene. This case series study was conducted retrospectively, giving a detailed description of the demographic and clinical information of these four cases, and reflecting our experience with this subset of patients. All these cases have been treated at the King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, and were identified by their clinical and laboratory markers that favor JBS. A novel homozygous missense mutation c.2075 T > C (p. lle692Thr) in exon 18 (UBR1: NM_174916.3) was identified and confirmed by Sanger sequencing in all our cases outlined in this paper. These presented cases illustrate the phenotypic variability and complexity of JBS and the importance of physical examination to reach a diagnosis. The identified novel mutation in this study broadens the spectrum of UBR1 mutations that contribute to JBS.

A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with osteogenesis imperfecta.

OBJECTIVES: Osteogenesis imperfecta (OI) is a heterogeneous group of inherited connective tissue disorders, characterised by skeletal fragility. Patients with OI may also exhibit extra-skeletal features like blue or grey scleral colour, fragile skin, easy bruising, joint laxity, short stature, deafness, cardiac valve abnormalities and abnormal pulmonary function. The objective of this study is to describe genetic mutations, prevalence of hearing issues, cardiac complications and impaired pulmonary function in children with OI. METHODS: This is a cross-sectional study of 23 Saudi children aged 6 months to 18 years who were diagnosed with OI. The revised Sillence classification (2,105) was used to classify the OI type. Whole exome sequencing was performed for genetic mutations. The hearing was assessed by either pure-tone audiometry and/or otoacoustic emission testing. Cardiac defects were screened by echocardiograms. Spirometry was performed to assess pulmonary function. Data were analysed with descriptive statistics. RESULTS: Based on the Sillence classification, 16 patients had OI type III, 6 had type IV and 1 had type I. Of the18 patients who had genetic sequencing, 66.6% had autosomal dominant and 33.3% had autosomal recessive mutations. Among children who had screening, hearing loss was diagnosed in 53% (9/17), congenital cardiac malformations in 26% (5/19) and restrictive lung disease in 70% (7/10). CONCLUSIONS: We found significant extra-skeletal features and a high yield of genetic mutations associated with OI. We suggest further studies to develop a screening protocol for extra-skeletal features in children with OI.

Complications After Surgical Repair of Congenital Heart Disease in Infants. An Experience From Tertiary Care Center.

OBJECTIVES: This study aimed to describe the incidence and spectrum of postoperative complications in infants who underwent their first cardiac surgery for the repair of congenital heart diseases. METHODS: This is a single-center retrospective study. Data of infants admitted to King Faisal Specialist Hospital & Research Center; Jeddah; Saudi Arabia, from January 2015 to December 2019 who underwent the first cardiac procedure for congenital heart disease at an age of less than 3 months, were analyzed. The primary outcome is the prevalence and spectrum of postoperative complications during hospitalization. Data were analyzed by using descriptive and analytical statistics using SAS software version 9.4. RESULTS: Data of 130 procedures were analyzed. The most frequent procedure performed was the Norwood procedure (31.5%), aortic coarctation repair (13.8%), arterial switch operation (13%), and Blalock-Taussig and central shunts (10%). The overall postprocedural complications were reported in 96 (73.8%) of the procedures. The most frequent complications were prolonged postoperative mechanical ventilation (27%), pleural effusion (21%), excessive bleeding (19%), cardiac arrest (18%), and systemic infections (18%). CONCLUSION: Cardiac surgery for congenital heart disease in young infants has a substantial risk for postoperative complications. The high incidence of these complications in these cases makes necessary attention to prove the outcomes in the cardiac centers.