Alzahrani Alshaimaa, Alshalan Maha, Alfurayh Mohammed, Bin Akrish Abdulaziz, Alsubeeh Najlaa A, Al Mutairi Fuad
Genetic and Precision Medicine Department, King Abdullah Specialized Children Hospital, King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNGHA), Riyadh, Saudi Arabia.
College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Front Neurol. 2023 Apr 14;14:1131490. doi: 10.3389/fneur.2023.1131490. eCollection 2023.
Calcium ions are involved in several human cellular processes; nevertheless, the relationship between calcium channelopathies (CCs) and autism spectrum disorder (ASD) or intellectual disability (ID) has been previously investigated. We delineate the spectrum of clinical phenotypes and the symptoms associated with a syndrome caused by an inherited gain-of-function mutation in in a family with a history of neuropsychiatric disorders. We also review the clinical and molecular phenotype of previously reported variants of .
We report the case of a 9-year-old female patient, diagnosed with ASD, severe ID, hyperactivity, and aggressive impulsive behaviors. The father, who was a 65-year-old at the time of his death, had ID and developed major depressive disorder with catatonic features and nihilistic delusion, followed by rapidly progressive dementia. He died after experiencing prolonged seizures followed by post-cardiac arrest. The patient's sister was a 30-year-old woman, known to have a severe ID with aggressive behaviors and sleep disorders. The sister has been diagnosed with bipolar disorder and psychosis. Through whole exome sequencing, a heterozygous previously identified and functionally characterized missense likely pathogenic variant was identified in the gene NM_001128840.3: c.2015C > T (p.Ser672Leu). These findings are consistent with the genetic diagnosis of autosomal dominant primary aldosteronism, seizures, and neurological abnormalities. This variant was found in the heterozygous status in the patient, her father, and her affected sister.
This case report will help to determine the key clinical features of this syndrome, which exhibits variable clinical presentations.
钙离子参与多种人体细胞过程；然而，此前已有关于钙通道病（CCs）与自闭症谱系障碍（ASD）或智力残疾（ID）之间关系的研究。我们描述了一个有神经精神疾病家族史的家庭中，由遗传性功能获得性突变引起的一种综合征的临床表型谱及相关症状。我们还回顾了先前报道的该基因变体的临床和分子表型。
我们报告了一名9岁女性患者的病例，该患者被诊断为患有自闭症谱系障碍、重度智力残疾、多动以及攻击冲动行为。患者的父亲在去世时65岁，患有智力残疾，并发展为伴有紧张症特征和虚无妄想的重度抑郁症，随后出现快速进展性痴呆。他在经历长时间癫痫发作后心脏骤停死亡。患者的姐姐是一名30岁女性，已知患有重度智力残疾并伴有攻击行为和睡眠障碍。姐姐被诊断患有双相情感障碍和精神病。通过全外显子组测序，在基因NM_001128840.3中鉴定出一个杂合的、先前已鉴定且功能特征明确的错义可能致病变体：c.2015C＞T（p.Ser672Leu）。这些发现与常染色体显性原发性醛固酮增多症、癫痫发作和神经学异常的基因诊断一致。该变体在患者、其父亲和受影响的姐姐中均为杂合状态。
本病例报告将有助于确定该综合征的关键临床特征，该综合征表现出多种临床表现。
