Pediatric Neurology Unit, 70492Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
Department of Neurology, 6453Royal Children's Hospital, Melbourne, Australia.
J Child Neurol. 2021 Feb;36(2):152-158. doi: 10.1177/0883073820960314. Epub 2020 Oct 4.
Chudley-McCullough syndrome, a rare autosomal recessive disorder due to pathogenic variants in the (G-protein signaling modulator 2) gene, is characterized by early-onset sensorineural deafness and a typical combination of brain malformations, including ventriculomegaly, (partial) agenesis of the corpus callosum, cerebellar dysplasia, arachnoid cysts, frontal subcortical heterotopia, and midline polymicrogyria. When hearing loss is managed early, most patients have minor or no impairment of motor and cognitive development, despite the presence of brain malformations. We report 2 cases of Chudley-McCullough syndrome, one presenting with congenital deafness and normal development except for speech delay and one presenting prenatally with ventriculomegaly and an atypical postnatal course characterized by epileptic spasms, deafness, and moderate intellectual disability. These highlight the challenges faced by clinicians when predicting prognosis based on pre- or postnatal imaging of brain malformations. We have also reviewed the phenotype and genotype of previous published cases to better understand Chudley-McCullough syndrome.
Chudley-McCullough 综合征是一种罕见的常染色体隐性遗传病，由 (G 蛋白信号调节因子 2) 基因的致病性变异引起，其特征是早发性感觉神经性耳聋和典型的脑畸形组合，包括脑室扩大、（部分）胼胝体发育不全、小脑发育不良、蛛网膜囊肿、额皮质下异位和中线多小脑回。当听力损失得到早期管理时，尽管存在脑畸形，但大多数患者的运动和认知发育仅有轻微或无损伤。我们报告了 2 例 Chudley-McCullough 综合征病例，1 例表现为先天性耳聋和正常发育，除了言语延迟外，另 1 例在产前表现为脑室扩大，随后出现癫痫发作、耳聋和中度智力残疾等非典型的围生期病程。这些病例突出了临床医生在基于脑畸形的产前或产后影像学来预测预后时所面临的挑战。我们还回顾了之前发表的病例的表型和基因型，以更好地理解 Chudley-McCullough 综合征。
