A novel likely pathogenic heterozygous HECW2 missense variant in a family with variable expressivity of neurodevelopmental delay, hypotonia, and epileptiform EEG patterns.

Pathogenic variants in HECW2 are extremely rare. So far, only 19 cases have been reported. They were associated with epilepsy, intellectual disability, absent language, hypotonia, and autism. As these cases were all de novo mutations, mostly presenting without identical variants, variable expressivity has never been investigated. Here, we describe the first family with the same novel variant in HECW2. A 19-year old female patient presented with bursts of generalized spike-wave discharges and intellectual disability. We performed next-generation-sequencing, to detect the genetic cause. Next-generation-sequencing revealed a novel likely pathogenic variant in HECW2 (c.3571C>T; p.Arg1191Trp) in the index patient, her mother and brother. They showed some similar phenotypic patterns with intellectual disability, hypotonia and generalized epileptiform patterns. However, the mother was less severely affected and epileptiform patterns were less frequent. The brother presented with additional autistic features. In contrast to previous cases, the speech of all individuals was only mildly impaired. This is the first case report of a family with the same novel likely pathogenic variant in HECW2 and as such provides insight into the phenotypic variability of this mutation. The expressivity of symptoms may be so mild that genetic and EEG analysis are needed to disclose the correct diagnosis.

Needle EMG induced muscle bleeding complication after guideline approved discontinuation of anticoagulation.

INTRODUCTION: Needle electromyography (EMG) is an essential part of electrodiagnosis (EDX) in neuromuscular disorders. As in all invasive procedures there is a risk of bleeding complications, but which is rare according to the current literature. Controlled, prospective studies that include patients under anticoagulation or antiplatelet therapy are lacking and would be difficult to conduct. CASE REPORTS: We describe two patients with no history of coagulopathy who developed an intramuscular hematoma after needle EMG. They had been under therapeutic anticoagulation but this had been discontinued, and their standard coagulation parameters had returned to normal prior to the EMG. One patient was found to have a rare genetic defect in thromboxane synthesis with associated markedly impaired platelet aggregation, while no obvious cause of the bleeding was found in the second patient. However, it could have been due to an unexpectedly strong anticoagulatory response to the oral anticoagulant apixaban. CONCLUSION: One must be aware of the increased risk of bleeding events in patients with therapeutic anticoagulation. These can occur even when the recommendations regarding discontinuation of anticoagulant drugs for the procedure have been followed. The patient must be actively questioned for ongoing use of NSAIDs, and if pain therapy is required alternatives with no antiplatelet activity should be given. A larger data pool of adverse EMG events would aid in risk assessment and decision making.