To date, all reports of pathogenic variants affecting the GTPase domain of the DNM1 gene have a clinically severe neurodevelopmental phenotype, including severe delays or intractable epilepsy. We describe a case with moderate developmental delays and self-resolved epilepsy.

The patient was followed by our neurology and genetics teams. After clinical examination and EEG to characterize the patient's presentation, we conducted etiologic workup including brain MRI, chromosomal microarray, genetic and metabolic investigations, and nerve conduction studies. Subsequently, we arranged an Intellectual Disability Plus Trio Panel.

Our patient presented with seizures at 2 days old, requiring phenobarbital. She also had hypotonia, mild dysmorphic features, and mild ataxia. Although initial workup returned unremarkable, the trio gene panel identified a de novo heterozygous pathogenic missense variant in the DNM1 GTPase domain. Now 4 years old, she has been seizure-free for 3 years without ongoing treatment and has nonsevere developmental delays (e.g., ambulates independently and speaks 2-word phrases).

Our case confirms that not all individuals with DNM1 pathogenic variants, even affecting the GTPase domain, will present with intractable epilepsy or severe delays. Expanding the known clinical spectrum of dynamin-related neurodevelopmental disorder is crucial for patient prognostication and counseling.

迄今为止，所有影响DNM1基因 GTPase 结构域的致病变异的报道都具有临床上严重的神经发育表型，包括严重的延迟或顽固性癫痫。我们描述了一个患有中度发育迟缓和自愈性癫痫的病例。

我们的神经病学和遗传学团队对患者进行了跟踪。在临床检查和 EEG 以描述患者的表现后，我们进行了病因检查，包括脑 MRI、染色体微阵列、遗传和代谢研究以及神经传导研究。随后，我们安排了智障加三人小组。

我们的患者在 2 天大时出现癫痫发作，需要使用苯巴比妥。她还有肌张力减退、轻度畸形特征和轻度共济失调。尽管最初的检查结果并不显着，但 trio 基因组在DNM1 GTPase 结构域中发现了一个从头杂合的致病性错义变体。现在 4 岁，在没有持续治疗的情况下，她已经 3 年没有癫痫发作，并且有非严重的发育迟缓（例如，独立行走和说 2 个单词的短语）。

我们的案例证实，并非所有具有DNM1致病变异的个体，即使影响 GTPase 结构域，都会出现顽固性癫痫或严重延迟。扩大已知的与动力相关的神经发育障碍的临床谱对于患者的预后和咨询至关重要。