X-linked intellectual disability can be diagnosed in about 10–12% of intellectually disabled males. In the past, mutations affecting the PAK3 gene (p21 protein-activated kinase 3, MIM#300142) have been associated with a non-syndromic form of X-linked intellectual disability, which has to date been identified in a limited number of families.

Since this neurodevelopmental disorder mostly afflicts males, descriptions of symptomatic female carriers are quite rare.

We describe a female patient with neurodevelopmental delay and a novel PAK3 variant. Interestingly, she manifests craniofacial anomalies, including microcephaly, representing the second reported microcephalic female but the first for whom a detailed clinical description is available. She also displays other uncommon clinical findings, which we illustrate.

Moreover, a comprehensive clinical and molecular review of all to date published patients has been made. 

This study contributes to further delineate the PAK3-related phenotype, which can be considered a non-syndromic X-linked intellectual disability, with seemingly recurrent craniofacial abnormalities.

大约 10-12% 的智障男性可以诊断出 X 连锁智力障碍。过去，影响PAK3基因（p21 蛋白激活激酶 3，MIM#300142）的突变与 X 连锁智力障碍的非综合征形式有关，迄今为止已在有限数量的家庭中发现了这种形式。

由于这种神经发育障碍主要影响男性，因此对有症状的女性携带者的描述非常罕见。

我们描述了一名患有神经发育迟缓的女性患者和一种新的PAK3变体。有趣的是，她表现出颅面异常，包括小头畸形，代表第二个报告的小头女性，但第一个有详细的临床描述。她还展示了其他不常见的临床发现，我们对此进行了说明。

此外，已经对所有迄今为止发表的患者进行了全面的临床和分子评估。 

该研究有助于进一步描述PAK3相关表型，该表型可被认为是一种非综合征性 X 连锁智力障碍，具有看似反复出现的颅面异常。