Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by rearrangements on chromosome 22q13.3 or sequence variants in SHANK3. Individuals with PMS caused by a 22q terminal deletion and a ring chromosome are at increased risk for Neurofibromatosis type 2 (NF2). However, the prevalence of NF2 in individuals with PMS and a r (22) is unknown.

Individuals with PMS and a r (22) chromosome evaluated at the Greenwood Genetic Center (GGC) or by international collaborators, or identified through the PMS International Registry (PMSIR) were contacted and participated in a clinical questionnaire. Forty-four families completed the questionnaire and consented for the study. Of the individuals with a r (22), 7 (16%) carried a diagnosis of NF2. The average age of diagnosis of r (22) was 18 years old in individuals with NF2 and three years old in individuals without NF2 (p-value <0.001). Clinical findings were similar among all individuals in our sample with the exception of hearing loss, present in 57% of individuals with NF2 and 8% of individuals without NF2 (p-value <0.01).

This is the largest clinical report of individuals with PMS and a r (22) chromosome. We show a diagnosis of NF2 in individuals with r (22) is not uncommon and may be under ascertained. Moreover, the presentation of NF2 in this cohort is variable and lifelong routine screening for features of NF2 in this population should be considered.

Phelan-McDermid综合征（PMS）是一种罕见的神经发育障碍，由22q13.3号染色体上的重排或SHANK3中的序列变异引起。由22 q末端缺失和环状染色体引起的PMS患者患2型神经纤维瘤病（NF2）的风险增加。但是，尚不清楚PMS和ar（22）患者中NF2的患病率。

在格林伍德遗传中心（GGC）或由国际合作者评估或通过PMS国际注册（PMSIR）鉴定的具有PMS和ar（22）染色体的个体进行了联系，并参加了临床问卷调查。四十四个家庭填写了调查表并同意进行研究。在患有ar（22）的个体中，有7名（16％）患有NF2。r（22）的平均诊断年龄在患有NF2的个体中为18岁，而在没有NF2的个体中为3岁（p值<0.001）。在我们的样本中，除听力损失外，所有患者的临床发现均相似，有57％的NF2患者和8％的无NF2患者（p值<0.01）。

这是患有PMS和ar（22）染色体的个体的最大临床报告。我们显示r（22）的个体中NF2的诊断并不罕见，可能尚待确定。此外，该人群中NF2的表现是可变的，因此应考虑终身对该人群中NF2的特征进行常规筛查。