PDF(Pubmed)
Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目标：PTEN，一个已知的抑癌基因,是神经发育的中介.在PTEN基因中具有种系致病变异的个体，分子定义为PTEN错构瘤综合征（PHTS），在童年时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,癫痫发作的频率和性质以及联合医疗服务的利用情况尚未描述。
方法：在美国的5个中心招募年轻的PHTS患者和兄弟姐妹对照，每6-12个月随访一次，平均2.1年。除了从护理人员那里获得的历史，进行了神经发育评估和结构化形态学检查，和脑部MRI的发现，接受治疗，并报道了癫痫的特点。
结果：纳入了107例PHTS患者（中位年龄8.7岁；范围3-21岁）和38例对照。ASD和癫痫在PHTS患者中常见（51％和15％，分别)，与ASD密切相关的全身性癫痫。癫痫患者通常需要两种抗癫痫药物。神经影像学显示，PHTS-ASD患者血管周围间隙明显，血管周围髓鞘减少。联合疗法使用频繁，涉及身体，职业,演讲,和社交技能疗法，89%的患者都有PHTS,不管ASD的诊断，至少使用一项服务。
结论：这种前瞻性，纵向研究强调了年轻PHTS患者的广泛神经系统。ASD在PHTS中很常见，患有癫痫，联合医疗服务被普遍使用。我们的发现为与家人就PHTS的神经系统结局进行护理讨论提供了信息。
方法：在美国的5个中心招募年轻的PHTS患者和兄弟姐妹对照，每6-12个月随访一次，平均2.1年。除了从护理人员那里获得的历史，进行了神经发育评估和结构化形态学检查，和脑部MRI的发现，接受治疗，并报道了癫痫的特点。
结果：纳入了107例PHTS患者（中位年龄8.7岁；范围3-21岁）和38例对照。ASD和癫痫在PHTS患者中常见（51％和15％，分别)，与ASD密切相关的全身性癫痫。癫痫患者通常需要两种抗癫痫药物。神经影像学显示，PHTS-ASD患者血管周围间隙明显，血管周围髓鞘减少。联合疗法使用频繁，涉及身体，职业,演讲,和社交技能疗法，89%的患者都有PHTS,不管ASD的诊断，至少使用一项服务。
结论：这种前瞻性，纵向研究强调了年轻PHTS患者的广泛神经系统。ASD在PHTS中很常见，患有癫痫，联合医疗服务被普遍使用。我们的发现为与家人就PHTS的神经系统结局进行护理讨论提供了信息。
