Background

PURA-related neurodevelopmental disorders (PURA-NDDs) include 5q31.3 deletion syndrome and PURA syndrome. PURA-NDDs are characterized by neonatal hypotonia, moderate to severe global developmental delay/intellectual disability (GDD/ID), facial dysmorphism, epileptic seizures, nonepileptic movement disorders, and ophthalmological problems. PURA-NDDs have recently been identified and underestimated in neurodevelopmental cohorts, but their diagnosis is still challenging.

Methods

We retrospectively reviewed the clinical characteristics, genetic spectrum, and diagnostic journey of patients with PURA-NDDs.

Results

We report 2 patients with 5q31.3 microdeletion and 5 with PURA pathogenic variants. They demonstrated hypotonia (7/7, 100%), feeding difficulties (4/5, 80%), and respiratory problems (4/7, 57%) in the neonatal period. All of them had severe GDD/ID and could not achieve independent walking and verbal responses. Distinctive facial features of open-tented upper vermilion, long philtrum, and anteverted nares and poor visual fixation and tracking with or without nystagmus were most commonly found (5/7, 71.4%). There were no significant differences in clinical phenotypes between 5q31.3 microdeletion syndrome and PURA syndrome. PURA-NDDs need to be considered as a differential diagnosis in individuals who show severe hypotonia, including feeding difficulties since birth and severe developmental retardation with distinctive facial and ophthalmological features.

Conclusions

Our data expands the phenotypic and genetic spectrum of PURA-NDD. Next-generation sequencing methods based on the detailed phenotypic evaluation would shorten the diagnostic delay and would help this rare disorder become a recognizable cause of neurodevelopmental delay.

中文翻译：

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扩大 PURA 相关神经发育障碍的临床表型和遗传谱

背景

PURA 相关神经发育障碍 (PURA-NDD) 包括 5q31.3 缺失综合征和 PURA 综合征。PURA-NDD 的特点是新生儿张力减退、中度至重度全球发育迟缓/智力残疾 (GDD/ID)、面部畸形、癫痫发作、非癫痫性运动障碍和眼科问题。最近在神经发育队列中发现并低估了 PURA-NDD，但它们的诊断仍然具有挑战性。

方法

我们回顾性回顾了 PURA-NDD 患者的临床特征、遗传谱和诊断过程。

结果

我们报告了 2 名 5q31.3 微缺失患者和 5 名PURA患者致病性变异。他们在新生儿期表现出张力减退（7/7, 100%）、喂养困难（4/5, 80%）和呼吸问题（4/7, 57%）。他们都患有严重的 GDD/ID，无法实现独立行走和言语反应。最常见的面部特征是开放式上朱红色、长人中和前倾的鼻孔以及视力固定和追踪不良，伴有或不伴有眼球震颤（5/7，71.4％）。5q31.3微缺失综合征和PURA综合征的临床表型没有显着差异。PURA-NDDs 需要被视为对表现出严重张力减退的个体的鉴别诊断，包括自出生以来的喂养困难和具有独特面部和眼科特征的严重发育迟缓。

结论

我们的数据扩展了 PURA-NDD 的表型和遗传谱。基于详细表型评估的下一代测序方法将缩短诊断延迟，并有助于这种罕见疾病成为神经发育延迟的一个可识别原因。