Genetic conditions comprise a wide spectrum of different phenotypes, rapidly expanding due to new diagnostic methodologies. Patients’ facial features and clinical history represent the key elements leading clinicians to the right diagnosis.

CDKL5-early onset epilepsy and Pitt-Hopkins syndrome are two well-known genetic conditions, with a defined phenotype sharing some common characteristics like early-onset epilepsy and hyperventilation episodes. Whilst facial features represent a diagnostic handle in patients with Pitt-Hopkins syndrome, clinical history is crucial in patients carrying a mutation in CDKL5.

Here we present the clinical case of a girl evaluated for the first time when she was 24- years old, with a clinical phenotype mimicking Pitt-Hopkins syndrome. Her facial features have become coarser while she was growing up, leading geneticists to raise different clinical hypotheses and to perform several molecular tests before getting the diagnosis of CDKL5-early-epileptic encephalopathy.

This finding highlights that although typical facial gestalt has not so far extensively been described in CDKL5 mutated adult patients, peculiar facial features could be present later in life and may let CDKL5-related disorder mimic Pitt Hopkins. Thus, considering atypical Rett syndrome in the differential diagnosis of Pitt Hopkins syndrome could be important to solve complex clinical cases.

遗传条件包括各种各样的不同表型，由于新的诊断方法而迅速扩大。患者的面部特征和临床病史是导致临床医生正确诊断的关键因素。

CDKL5早期发作性癫痫和Pitt-Hopkins综合征是两个众所周知的遗传病，具有明确的表型，具有一些共同特征，如早期发作性癫痫和过度换气发作。虽然面部特征代表了Pitt-Hopkins综合征患者的诊断能力，但临床病史对于携带CDKL5突变的患者至关重要。

在这里，我们介绍了一个女孩的临床病例，该女孩在24岁时首次进行了评估，其临床表型类似于Pitt-Hopkins综合征。她的成长过程中，她的面部特征变得更加粗糙，导致遗传学家提出了不同的临床假设，并进行了多种分子检测，然后才诊断出CDKL5早期癫痫性脑病。

这一发现突出表明，尽管到目前为止尚未在CDKL5突变的成年患者中广泛描述典型的面部格式塔，但在生命的后期可能会出现特殊的面部特征，并可能使CDKL5相关的疾病模仿Pitt Hopkins。因此，在Pitt Hopkins综合征的鉴别诊断中考虑非典型的Rett综合征对于解决复杂的临床病例可能很重要。