遺伝性周期性四肢麻痺

OBJECTIVE: To estimate allele frequencies for genetic diseases in the American Quarter Horse (QH), including hyperkalemic periodic paralysis (HYPP), type 1 polysaccharide storage myopathy (PSSM1), malignant hyperthermia (MH), myosin-heavy chain myopathy (MYHM), glycogen branching enzyme deficiency (GBED), hereditary equine regional dermal asthenia (HERDA), and equine juvenile spinocerebellar ataxia (EJSCA), and to compare these frequencies over time among elite performance subgroups and a random cohort of registered horses. METHODS: In this prospective genetic survey, DNA was extracted from 300 elite performance QHs in 7 popular disciplines and 300 randomly selected QHs born between 2020 and 2024. Genotyping was performed with commercially available assays. Allele, carrier, and affected frequencies were calculated as proportion ± SE, compared across disciplines, and compared to a 2009 study by Tryon et al. RESULTS: Genotyping the top-performing QHs identified high HYPP (0.318 ± 0.050) and PSSM1 (0.386 ± 0.052) frequencies in halter horses. Glycogen branching enzyme deficiency frequency was high in reining horses (0.109 ± 0.032), and HERDA was high in cutting horses (0.135 ± 0.035). Genotyping randomly selected QHs identified low PSSM1 (0.012 ± 0.004) and high myosin-heavy chain myopathy frequencies (0.066 ± 0.010). Many of these allele frequencies in the random population have not changed over time (HYPP, GBED, HERDA) but have changed within specific subgroups. Equine juvenile spinocerebellar ataxia allele frequencies were low but detectable in the random, reining, and cutting populations. CONCLUSIONS: Disease allele frequencies in QHs are highly variable between performance subgroups. CLINICAL RELEVANCE: The establishment of allele frequencies allows for longitudinal monitoring to determine how genetic testing results are being utilized.

BACKGROUND: Bidirectional ventricular tachycardia is a rare electrocardiographic (ECG) finding, associated with a restricted group of clinical conditions, particularly hereditary channelopathies. CASE SUMMARY: An 11-year-old girl, asymptomatic from a cardiovascular point of view, was identified by family screening after detection in her father of a pathogenic variant in the KCNJ2 gene. The admission ECG showed bidirectional ventricular tachycardia. Clinical investigation revealed periodic paralysis and skeletal dysmorphisms, confirming a diagnosis of Andersen-Tawil syndrome. Pharmacological treatment significantly reduced the arrhythmic burden, with reverse ventricular remodeling at follow-up. DISCUSSION: This case illustrates the central role of ECG as a diagnostic tool in rare cardiovascular diseases, allowing early recognition, targeted genetic investigation, and prevention of arrhythmia-induced cardiomyopathy. TAKE HOME MESSAGES: Bidirectional ventricular tachycardia is a distinct ECG pattern that should raise suspicion of Andersen-Tawil syndrome and warrants genetic evaluation with cascade family screening. In this patient, the combination of propafenone and beta-blocker therapy was associated with suppression of bidirectional ventricular tachycardia, significant reduction in ventricular arrhythmic load, and reversal of tachycardiomyopathy, suggesting a potential therapeutic alternative when flecainide is not available.

Andersen-Tawil syndrome (ATS) is a rare, hereditary channelopathy characterized by periodic paralysis, cardiac arrhythmias, and sometimes developmental anomalies. No association with hematologic malignancies has previously been reported. We describe the case of a 27-year-old man with genetically confirmed Type 1 ATS who developed T-cell acute lymphoblastic leukemia. He was treated according to the GRAALL-2014 protocol and achieved sustained complete molecular remission without allogeneic transplantation after 3.5 years of follow-up. Management required careful adaptation to mitigate ATS-related risks. Specifically, QT-prolonging and neurotoxic agents were avoided or substituted, glucose infusions were minimized, and acetazolamide was introduced early. Despite exposure to high-dose corticosteroids and anthracyclines, only moderate, self-limited paralytic episodes occurred during intensive phases. During maintenance, ventricular ectopy and QT prolongation prompted chemotherapy dose adjustments and beta-blocker therapy, leading to rapid normalization. This case highlights the feasibility of delivering intensive chemotherapy in ATS with tailored supportive care. Although likely coincidental, this unprecedented association raises questions about potential links between ion channel dysfunction and leukemogenesis.

Reliable pre-implantation sex determination and genetic screening enables informed embryo transfer decisions in equine breeding while avoiding later interventions. We developed a streamlined workflow that couples rapid whole genome amplification (WGA) with a multiplex real-time PCR targeting ETSTY5 as a Y-specific marker and UBC as an autosomal control. On purified equine DNA, sex was correctly assigned down to 10 pg gDNA and to a single fibroblast cell. Direct testing of embryo biopsies without WGA yielded inconsistent results, whereas introducing a short WGA step produced tight allelic-discrimination clusters and 100% diagnostic calls, including in cloned embryos of known sex. The same WGA product supported targeted genotyping for inherited disease screening of hyperkalemic periodic paralysis (HYPP) and hereditary equine regional dermal asthenia (HERDA) alleles. This WGA plus real-time PCR pipeline supports robust and practical embryo sexing and targeted pre-implantation genetic diagnostics within in vitro produced equine embryo and embryo transfer workflows.

Hypokalemic periodic paralysis (HypoPP) occurs in calcium and sodium ion channelopathy, which is a rare presentation following certain triggers. This typically hereditary condition leads to episodic acute muscle weakness associated with hypokalemia, which can later present as permanent weakness. This article presents the case of a 37-year-old male who developed bilateral lower limb weakness associated with severe hypokalemia following intramuscular administration of 8 mg dexamethasone. HypoPP, though not common, should be evaluated in patients following treatment with glucocorticoids. These patients present with typical symptoms that can be managed accordingly.