Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, 44195, USA.
Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, 44195, USA.
Ann Clin Transl Neurol. 2024 May;11(5):1301-1309. doi: 10.1002/acn3.52046. Epub 2024 Mar 19.
PTEN, a known tumor suppressor gene, is a mediator of neurodevelopment. Individuals with germline pathogenic variants in the PTEN gene, molecularly defined as PTEN hamartoma tumor syndrome (PHTS), experience a variety of neurological and neuropsychiatric challenges during childhood, including autism spectrum disorder (ASD). However, the frequency and nature of seizures and the utilization of allied health services have not been described.
Young patients with PHTS and sibling controls were recruited across five centers in the United States and followed every 6-12 months for a mean of 2.1 years. In addition to the history obtained from caregivers, neurodevelopmental evaluations and structured dysmorphology examinations were conducted, and brain MRI findings, received therapies, and epilepsy characteristics were reported.
One hundred and seven patients with PHTS (median age 8.7 years; range 3-21 years) and 38 controls were enrolled. ASD and epilepsy were frequent among patients with PHTS (51% and 15%, respectively), with generalized epilepsy strongly associated with ASD. Patients with epilepsy often required two antiseizure medications. Neuroimaging revealed prominent perivascular spaces and decreased peritrigonal myelination in individuals with PHTS-ASD. Allied therapy use was frequent and involved physical, occupational, speech, and social skills therapies, with 89% of all patients with PHTS, regardless of ASD diagnosis, utilizing at least one service.
This prospective, longitudinal study highlights the wide neurological spectrum seen in young individuals with PHTS. ASD is common in PHTS, comorbid with epilepsy, and allied health services are used universally. Our findings inform care discussions with families about neurological outcomes in PHTS.
PTEN 是一种已知的肿瘤抑制基因，是神经发育的介质。具有 PTEN 基因种系致病性变异的个体，分子上定义为 PTEN 错构瘤肿瘤综合征（PHTS），在儿童期经历各种神经和神经精神挑战，包括自闭症谱系障碍（ASD）。然而，尚未描述癫痫发作的频率和性质以及联合保健服务的利用情况。
在美国的五个中心招募了患有 PHTS 的年轻患者及其兄弟姐妹对照者，并在平均 2.1 年的时间内每 6-12 个月进行一次随访。除了从照顾者那里获得病史外，还进行了神经发育评估和结构化畸形检查，并报告了脑 MRI 结果、接受的治疗和癫痫特征。
共纳入了 107 例 PHTS 患者（中位数年龄 8.7 岁；范围 3-21 岁）和 38 名对照者。PHTS 患者中 ASD 和癫痫发作较为常见（分别为 51%和 15%），全身性癫痫与 ASD 密切相关。癫痫发作患者通常需要两种抗癫痫药物。神经影像学显示 PHTS-ASD 患者的血管周围空间明显突出，周围脑膜的髓鞘形成减少。联合治疗的应用较为频繁，涉及物理、职业、言语和社会技能治疗，89%的 PHTS 患者，无论 ASD 诊断如何，都至少使用了一种服务。
这项前瞻性、纵向研究强调了 PHTS 年轻患者中广泛的神经学表现。ASD 在 PHTS 中很常见，与癫痫共病，并且普遍使用联合保健服务。我们的研究结果为与 PHTS 患者家庭讨论神经学结局提供了信息。
