Familial Hemiplegic Migraine with Prolonged Coma and Hyperthermia: ATP1A2 Gene Mutation Case Report in a Single Saudi Family.

Background: Familial hemiplegic migraine (FHM) is a rare disorder presented commonly with coma, hyperthermia, and headache. FHM is usually associated with fully reversible motor weakness as a specific symptom of aura. Seizure and fever are the secondary features observed. All the affected individuals were subjected to several laboratory tests. Case presentation: Three sisters diagnosed with type 2 familial hemiplegic migraines presenting features such as coma and hyperthermia. The brain (MRI) revealed focal subtle cortical swelling, Electroencephalography (EEG) showed unilateral slowing, while no signs of infectious disease were observed. Molecular and genetic tests using whole exome sequencing (WES) identified a novel heterozygous mutation (c.2450T>A p.Ile817Asn) in the exon 18 of the ATP1A2 gene (NM_000702.3). The variant segregated with the disease phenotype within the family. Conclusion: The current study report for the first time, a Saudi family with migraine coma having a novel heterozygous AT1A2 mutation. [JBCGenetics 2019; 2(1.000): 85-90

Teaching Clinical Reasoning: An Experiment Comparing the Effects of Small-group Hypothetico-deduction Versus Self-explanation

Introduction: Research on the effectiveness of approaches for the teaching of clinical reasoning is scarce. A recent study showed hypothetico-deduction to be slightly more beneficial than self-explanation for students’ diagnostic performance. An account for this difference was unclear. This study investigated whether hypothetico-deduction leads to consideration of more alternative diagnoses while practicing with cases, and whether its advantage over self-explanation remains when diseases slightly different from the ones previously studied are tested. Methods: One-hundred thirty-nine 2nd-year students from a six-year medical school participated in a two-phase experiment. In the learning phase, they worked in small groups on five clinical vignettes of cardiovascular diseases by following different approaches depending on their experimental condition. Students under the self-explanation condition provided the most likely diagnosis and pathophysiological explanation for the clinical findings. Students under the hypothetico-deduction condition hypothesized about plausible diagnoses for clinical findings presented sequentially. In a one-week-later test, all students diagnosed eight cases of cardiovascular diseases with clinical presentations similar to the ones previously studied but different diagnoses. Results: The hypothetico-deduction condition generated more alternative diagnoses in the learning phase than the selfexplanation condition, F(1,177) = 199.51, p =.001, η2 = 0.53; the effect size was large. A small difference in favour of hypothetico-deduction was observed in the proportion of accurate diagnoses: F(1,138) = 4.08, p =.05, η2 = 0.03. Discussion: Relative to self-explanation, hypothetico-deduction induced consideration of more alternative diagnoses during practice with cases

Teaching clinical reasoning through hypothetico-deduction is (slightly) better than self-explanation in tutorial groups: An experimental study

Background Self-explanation while individually diagnosing clinical cases has proved to be an effective instructional approach for teaching clinical reasoning. The present study compared the effects on diagnostic performance of self-explanation in small groups with the more commonly used hypothetico-deductive approach. Methods Second-year students from a six-year medical school in Saudi Arabia (39 males; 49 females) worked in small groups on seven clinical vignettes (four criterion cases representing cardiovascular diseases and three ‘fillers’, i.e. cases of other unrelated diagnoses). The students followed diffe

Further delineation of the phenotypic spectrum of ISCA2 defect: A report of ten new cases

Iron-Sulfur Cluster (ISC) biogenesis is a vital cellular process required to produce various ISC-containing proteins. These ISC proteins are responsible for essential functions such as glycine cleavage and the formation of lipoic acid, an essential cofactor of respiratory chain complexes. Defects in ISC biogenesis lead to multiple mitochondrial dysfunction syndromes including: ISCA2 with infantile onset leukodystrophy. Recently, a founder mutation, c.229G > A, p.Gly77Ser in ISCA2 was reported to cause Multiple Mitochondrial Dysfunction Syndrome type 4. In a retrospective review of children diagnosed with the ISCA2 defect, we were able to identify ten new patients who were not reported previously with the identical founder mutation. High CSF glycine levels and elevated glycine peaks on MR spectroscopy were demonstrated in all tested probands. All patients were between 3 and 7 months of age with a triad of neurodevelopmental regression, nystagmus and optic atrophy and leukodystrophy. MRI findings were typical in the patients with diffuse, abnormal white matter signal in the cerebrum, cerebellum, brain stem and spinal cord. The patients ended up in a vegetative state, and often premature death due to respiratory infections. We alert clinicians to consider the ISCA2 defect as a differential diagnosis of infantile onset leukodystrophies affecting the brain as well as the spinal cord, especially in the presence of elevated CSF glycine or elevated glycine peaks in MR spectroscopy

Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome

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