Fifty random genetically unstudied families (limb-girdle muscular dystrophy (LGMD)/myopathy) were screened with a gene panel incorporating 759 OMIM genes associated with neurological disorders. Average coverage of the CDS and 10 bp flanking regions of genes was 99 %. All families were referred to the Neurosciences Clinic of King Faisal Specialist Hospital and Research Centre, Saudi Arabia. Patients presented with muscle weakness affecting the pelvic and shoulder girdle. Muscle biopsy in all cases showed dystrophic or myopathic changes. Our main objective was to evaluate a neurological gene panel as a first-line diagnostic test for LGMD/myopathies. Our panel identified the mutation in 76 % of families (38/50; 11 novel). Thirty-four families had mutations in LGMD-related genes with four others having variants not typically associated with LGMD. The majority of cases had recessive inheritance with homoallelic pathogenic variants (97.4 %, 37/38), as expected considering the high rate of consanguinity in the study population. In one case, we detected a heterozygous mutation in DNAJB responsible for LGMD-1E. Our cohort included seven different subtypes of LGMD2. Mutations of DYSF were the most commonly identified cause of disease followed by that in CAPN3 and FKRP. Non-LGMD myopathies were due to mutations in genes associated with congenital disorder of glycosylation (ALG2), rigid spine muscular dystrophy 1 (SEPN1), inclusion body myopathy2/Nonaka myopathy (GNE), and neuropathy (WNK1). Whole exome sequencing (WES) of patients who remained undiagnosed with the neurological panel did not improve our diagnostic yield. Our neurological panel achieved a high clinical sensitivity (76 %) and is an effective first-line laboratory test in patients with LGMD and other myopathies. This sensitive, cost-effective, and rapid assay significantly assists clinical practice especially in these phenotypically and genetically heterogeneous disorders. Moreover, the application of the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) guidelines applied in the classification of variant pathogenecity provides a clear interpretation for physicians on the relevance of such findings.

Context: Familial non-medullary thyroid cancer (NMTC) occurs either as part of known hereditary syndromes or as a non-syndromic isolated hereditary tumor. Although the genes underlying the syndromic type of NMTC have been identified in most syndromes, no clear underlying gene has been identified in the non-syndromic NMTC. Recently, a c.1601G>A, p.G534E mutation in the HABP2 gene was reported to be the underlying genetic defect in a family with 7 members affected by NMTC. The G534E variant has also been reported to occur in about 4.7% of cases of the Thyroid Cancer Genome Atlas (TCGA) database. Objectives: To explore whether the recent finding of G534E genetic variant can be replicated in a large sample of NMTC including 11 members of 4 unrelated families with familial NMTC and 509 cases of sporadic pediatric (63 cases) and adult NMTC (446 cases). Methods: We screened all exons and exon-intron boundaries of HABP2 in 11 members of 4 families with familial non-syndromic NMTC using DNA isolated from peripheral leucocytes, PCR and direct sequencing. We also screened specifically for the G534E variant in 229 of sporadic NMTC using DNA isolated from peripheral leucocytes and an additional 217 cases of NMTC using DNA isolated from formalin fixed paraffin embedded tumor tissues. As a control cohort, we screened 190 healthy individuals without known thyroid disease for the presence of the G534E variant using DNA isolated from peripheral leucocytes. Results: None of the familial NMTC carried HABP2 mutations. Of 509 sporadic NMTC, only one case (0.2%) harbored the G534E variant. Similarly, only one case (0.5%) of the control group harbored the G534E variant. Conclusion: In this study, HABP2 mutations were not found in familial NMTC and the G534E variant is not the underlying genetic defect in a large sample of sporadic NMTC from the Middle East.

Primary retroperitoneal teratomas involving adrenal glands are exceedingly uncommon accounting for only 4% of all primary teratomas. They are more common in childhood and rarely occur in adults. Only a very few case reports have been documented in literature so far. Herein, we report a mature (benign) cystic retroperitoneal teratoma in the region of left adrenal gland in a 22-year-old otherwise healthy male patient who presented with a 1-month history of left flank pain. In addition, a literature review on teratomas is included.

Autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy (APECED) is a rare autosomal recessive disorder caused by mutations in the autoimmune regulator gene (AIRE). Terminal 4q deletion is also a rare cytogenetic abnormality that causes a variable syndrome of dysmorphic features, mental retardation, growth retardation, and heart and limb defects. We report a 12‐year‐old Saudi boy with mucocutaneous candidiasis, hypoparathyroidism, and adrenocortical failure consistent with APECED. In addition, he has dysmorphic facial features, growth retardation, and severe global developmental delay. Patient had late development of chronic renal failure. The blastogenesis revealed depressed lymphocytes′ response to Candida albicans at 38% when compared to control. Chromosome analysis of the patient revealed 46,XY,del(4)(q33). FISH using a 4p/4q subtelomere DNA probe assay confirmed the deletion of qter subtelomere on chromosome 4. Parental chromosomes were normal. The deleted array was further defined using array CGH. AIRE full gene sequencing revealed a homozygous mutation namely 845_846insC. Renal biopsy revealed chronic interstitial nephritis with advanced fibrosis. In addition, there was mesangial deposition of C3, C1q, and IgM. This is, to the best of our knowledge, the first paper showing evidence of autoimmune nephropathy by renal immunofluorescence in a patient with APECED and terminal 4q deletion.

Mucormycosis is the third most common invasive fungal infection that particularly occurs in immunocompromised patients. Intracranial and extracranial arteriovenous vasculopathy is a complication that makes this disease more complex and difficult to treat. We describe a 23-year-old female, who presented to her local hospital with acute blindness and diabetic ketoacidosis-induced coma requiring intensive care treatment. She was found to have lesions in the nasal sinuses, orbit, and frontal base. The left carotid artery was occluded from its origin in the neck to the supraclinoid segment and left cavernous sinus involvement. No cerebral infarction was noted. Biopsies obtained by endonasal debridement confirmed mucormycosis. In addition to antimicrobial therapy, she underwent several multidisciplinary approaches to treat her disease. Multiple endonasal, and cranial procedures were done including bilateral orbital exenteration. After prolonged treatment on the intensive care unit she made a remarkable recovery to the point where she was communicating verbally and had normal limb movements and later discharged home. She remained alive and well for two months, but later succumbed to a recurrence of her disease. In conclusion, mucormycosis-induced vasculopathy is a complex problem, which merits aggressive treatment of this invasive disease. It is normally regarded as an indicator of grave prognosis.

Background: Atypical teratoid rhabdoid tumor is an uncommon aggressive central nervous system tumor. All retrospective series have shown a short mean overall survival rate. Considering the rarity of the disease, few prospective clinical trials addressed treatment recommendations for such aggressive tumors, and consequently no definitive treatment guidelines have been established. In this study, we are reviewing our experience in treating atypical teratoid rhabdoid tumor patients. Methods: We reviewed the medical charts of 43 patients with atypical teratoid rhabdoid tumor who were treated in King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, between 1996 and 2013. We evaluated the overall survival rate and the influence of different clinical features and treatment protocols on survival. Results: The median overall survival time was 16.9 months (95% Confidence Interval, 5.2–32.9 months) with an estimated 2- and 5-year overall survival of 41.9% ± 9.6 and 27.9% ± 9.2, respectively. Patients receiving trimodal treatment (surgery, chemotherapy, and radiotherapy) exhibited significantly better median overall survival time compared to their counterparts (P value < .001). Conclusions: Atypical teratoid rhabdoid tumor is rare and aggressive central nervous system tumor. Despite the limitations of the study, our results support several of clinical practice development. Utilization of postoperative radiotherapy and the adoption of trimodal therapy are associated with significant improvement of median survival. Prompt management with aggressive trimodal therapy should be the standard for future treatment protocols.