Embryonal tumor with multilayered rosettes: a report of a rare case.

The authors report a case of an embryonal tumor with multilayered rosettes (ETMR) in an 18-month-old female infant who presented with gait imbalance and progressive left-sided weakness for 2 months. ETMR is a rare small round blue cell aggressive tumor of the central nervous system characterized by the amplification of the C19MC region on chromosome 19 (Chr19q13.42). This report in detail the clinical-radiologic and histopathological workup and diagnosis. Because ETMRs are newly described rare pediatric central nervous system tumors with only a few reported cases, we aim to document this typical case to add to the existing data on these tumors.

Phenotypic and genotypic analysis of limb-Girdle muscular dystrophy type 2B.

Dysferlinopathies are rare autosomal recessive muscular dystrophies caused by mutation in the dysferlin (DYSF) gene, resulting in varied phenotype. In this case report, we review a 26-year-old diabetic male patient who presented to hospital suffering from progressive muscle weakness. We confirmed the diagnosis of dysferlinopathy with phenotype of limb girdle muscular dystrophy, followed by a muscle biopsy, immunohistochemistry and a molecular technique, exome sequencing. The specific homozygous mutations in DYSF and heterozygous mutation PSAP genes identified in the present case of LGMD-2B are found in the Saudi population.

Prevalence of biopsy-proven nonalcoholic fatty liver among patients with gallstone disease.

BACKGROUND/AIM: Gallstone disease (GD) and nonalcoholic fatty liver disease (NAFLD) are associated with metabolic syndrome. Despite the benign nature of NAFLD, 10% of patients may develop advanced fibrosis and cirrhosis. We aimed to identify the prevalence and factors associated with NAFLD among GD patients in the Saudi population. PATIENTS AND METHODS: This is a single-center, observational cohort study that included patients seen in general surgery clinics at our institution from 2011 to 2017. All liver biopsies were taken at the same time as the cholecystectomy. Demographical and clinical data were prospectively collected from the study population. RESULTS: Of the 301 GD patients in the study, 15% had a normal body mass index (BMI), 29% were overweight, and 56% were obese. There were 143 (47.8%) patients with NAFLD, of which 125 (41.8%) showed steatosis and 18 (6%) had nonalcoholic steatohepatitis. There was a significant positive correlation between NAFLD and age (r = 0.243; P < 0.0001), and BMI (r = 0.242; P < 0.0001). Obese patients with BMI 30-40 kg/m[2] were 2.403 (P = 0.039) more likely to have NAFLD compared with normal BMI patients, and this value increased to 6.145 (P = 0.002) in patients with BMI >40 kg/m[2]. Additionally, patients with T2DM were 2.839 times (P = 0.015) more likely to have NAFLD compared with those who did not. CONCLUSIONS: The prevalence of NAFLD among GD patients is high. High BMI and diabetes are independent factors associated with NAFLD in GD patients. The results suggest that there may be a need for routine liver biopsy in selected patients during cholecystectomy.

Brainstem encephalitis. A diagnostic dilemma.

Brainstem encephalitis (BE) is a rare, severe, and potentially life-threatening inflammation of the central nervous system. Brainstem encephalitis has multiple etiologies, which vary in treatment and outcomes. The current literature is generally focused on the infectious causes of BE, while little is known about the other entities, including cases with inconclusive diagnoses. Additionally, the outcomes of BE are not well documented. We present a case of an 18-year-old male who presented with progressive symptoms of brainstem involvement. His clinical investigations, including cerebrospinal fluid (CSF) analysis, were normal; magnetic resonance imaging (MRI) of the brain showed an enhancing medullary lesion, while tissue biopsy yielded no specific diagnosis. Multiple empirical treatments to address possible autoimmune and infectious processes were started with no significant improvement. He continued to deteriorate over a period of 12 weeks. Thereafter, following intensive supportive and rehabilitative care, he started to show slow signs of improvement.

Microscopic and ultrastructural changes of Müller's muscle in patients with simple congenital ptosis.

PURPOSE: To study microscopic and ultrastructural changes of Müller's muscle in patients with isolated congenital ptosis. METHODS: In this prospective, observational case-control study, Müller's muscle specimens were collected during ptosis surgical correction for 18 consecutive patients. Each specimen was divided into 2 parts. One part was embedded in formalin for light microscopy, and the other one was fixed in 3% glutaraldehyde for electron microscopy. A neuropathologist, serving as a masked evaluator, blindly reviewed all the different features for every case and counted the number of myocytes showing distinct myofilaments in the whole grid for every case. Statistical analysis using compare means and correlation tests was conducted to investigate potential associations and/or differences within and across groups. RESULTS: Twelve Müller's muscle specimens from patients with simple congenital ptosis of various severities and 6 specimens from patients with aponeurotic ptosis (controls) were collected and studied. Under light microscopy, congenital ptosis slides showed a small number of dispersed myocytes in a fibrotic background, whereas acquired ptosis slides showed a greater number of well-defined myocytes. Under electron microscopy, all congenital ptosis specimens had only a very small number of myocytes with clear, distinct myofilaments. Most myocytes in the aponeurotic ptosis group showed clear, distinct myofilaments, indicating a well-preserved muscle. No relationship existed between the number of clear, distinct myofilaments observed in the congenital ptosis group by transmission electron microscopy and patient age or ptosis severity. CONCLUSION: Substantial Müller's muscle atrophy was observed in patients with different severities of isolated congenital ptosis.

New findings in a global approach to dissect the whole phenotype of PLA2G6 gene mutations.

Mutations in PLA2G6 gene have variable phenotypic outcome including infantile neuroaxonal dystrophy, atypical neuroaxonal dystrophy, idiopathic neurodegeneration with brain iron accumulation and Karak syndrome. The cause of this phenotypic variation is so far unknown which impairs both genetic diagnosis and appropriate family counseling. We report detailed clinical, electrophysiological, neuroimaging, histologic, biochemical and genetic characterization of 11 patients, from 6 consanguineous families, who were followed for a period of up to 17 years. Cerebellar atrophy was constant and the earliest feature of the disease preceding brain iron accumulation, leading to the provisional diagnosis of a recessive progressive ataxia in these patients. Ultrastructural characterization of patients' muscle biopsies revealed focal accumulation of granular and membranous material possibly resulting from defective membrane homeostasis caused by disrupted PLA2G6 function. Enzyme studies in one of these muscle biopsies provided evidence for a relatively low mitochondrial content, which is compatible with the structural mitochondrial alterations seen by electron microscopy. Genetic characterization of 11 patients led to the identification of six underlying PLA2G6 gene mutations, five of which are novel. Importantly, by combining clinical and genetic data we have observed that while the phenotype of neurodegeneration associated with PLA2G6 mutations is variable in this cohort of patients belonging to the same ethnic background, it is partially influenced by the genotype, considering the age at onset and the functional disability criteria. Molecular testing for PLA2G6 mutations is, therefore, indicated in childhood-onset ataxia syndromes, if neuroimaging shows cerebellar atrophy with or without evidence of iron accumulation.

A 38-year old woman with a dural based lesion.

Isolated intracranial xanthogranulomas arising from the dura mater are extremely rare.We present a case of a symptomatic large right frontoparietal dura based intracranial xanthogranuloma in a 38-year-old female. Xanthogranulomas are benign non-Langerhans cell histiocytic lesions. They are frequently described in the skin of infants and children. Extracutaneous manifestations especially in the central nervous system are highly uncommon. Dural xanthogranulomas usually arise in association with familial hypercholesterolemia, with Erdheim Chester disease (ECD), and with Weber-Christian disease. Our case however, had no such associations. In this report, the authors describe the clinical, radiological and microscopic presentation of this case and the differential diagnoses of intracranial xanthogranuloma.

Efficient identification of novel mutations in patients with limb girdle muscular dystrophy.

Limb girdle muscular dystrophy type 2 (LGMD2) is a genetically heterogeneous autosomal recessive disorder caused by mutations in 15 known genes. DNA sequencing of all candidate genes can be expensive and laborious, whereas a selective sequencing approach often fails to provide a molecular diagnosis. We aimed to efficiently identify pathogenic mutations via homozygosity mapping in a population in which the genetics of LGMD2 has not been well characterized. Thirteen consanguineous families containing a proband with LGMD2 were recruited from Saudi Arabia, and for 11 of these families, selected individuals were genotyped at 10,204 single nucleotide polymorphisms. Linkage analysis excluded all but one or two known genes in ten of 11 genotyped families, and haplotype comparisons between families allowed further reduction in the number of candidate genes that were screened. Mutations were identified by DNA sequencing in all 13 families, including five novel mutations in four genes, by sequencing at most two genes per family. One family was reclassified as having a different myopathy based on genetic and clinical data after linkage analysis excluded all known LGMD2 genes. LGMD2 subtypes A and B were notably absent from our sample of patients, indicating that the distribution of LGMD2 mutations in Saudi Arabian families may be different than in other populations. Our data demonstrate that homozygosity mapping in consanguineous pedigrees offers a more efficient means of discovering mutations that cause heterogeneous disorders than comprehensive sequencing of known candidate genes.