Mittal Rea, Kumar Ashutosh, Ladda Roger, Mainali Gayatra, Aliu Ermal
Penn State Health College of Medicine, Hershey, USA.
Department of Pediatrics and Neurology, Penn State Health College of Medicine, Hershey, USA.
Child Neurol Open. 2021 Nov 10;8:2329048X211055330. doi: 10.1177/2329048X211055330. eCollection 2021 Jan-Dec.
Pitt Hopkins-like syndrome 1 (PTHLS1, OMIM # 610042) is an ultra-rare autosomal recessive condition with a prevalence of <1/1,000,000. Intragenic deletions of CNTNAP2 has been implicated in PTHLS1, however to our knowledge a compound heterozygous deletion of exon 4 and a c.1977_1989del13; p.V660Ffsx9 frameshift variant have not been published previously. In this case report, the proband is a seven year old female with PTHLS1, developmental delay, autism spectrum disorder, focal epilepsy, hypotonia, refractory errors, strabismus, and obstructive sleep apnea. Whole exome sequencing analysis revealed biallelic pathogenic variants of the CNTNAP2 gene. Proband has a three year old sister who has who has a similar phenotype including, developmental delay, epilepsy, gait abnormality, refractory errors, strabismus. Family variants were tested and she shared the same CNTNAP2 variants as her sister. The sisters described highlight two novel variants leading to PTHLS1. Genetic workup is essential in identification and management guidance in these populations.
皮特-霍普金斯样综合征1（PTHLS1，OMIM # 610042）是一种极为罕见的常染色体隐性疾病，患病率<1/1,000,000。CNTNAP2基因内的缺失与PTHLS1有关，然而据我们所知，外显子4的复合杂合缺失以及c.1977_1989del13；p.V660Ffsx9移码变异此前尚未见报道。在本病例报告中，先证者是一名患有PTHLS1的7岁女性，伴有发育迟缓、自闭症谱系障碍、局灶性癫痫、肌张力减退、难治性屈光不正、斜视和阻塞性睡眠呼吸暂停。全外显子测序分析揭示了CNTNAP2基因的双等位基因致病变异。先证者有一个3岁的妹妹，其具有相似的表型，包括发育迟缓、癫痫、步态异常、难治性屈光不正、斜视。对家族变异进行了检测，她与妹妹共享相同的CNTNAP2变异。所描述的这对姐妹凸显了导致PTHLS1的两种新变异。基因检查对于这些人群的识别和管理指导至关重要。
