Rubinstein-Taybi syndrome (RSTS) is a rare dominant disorder with intellectual disability, postnatal growth deficiency, and multiple congenital anomalies. Approximately 50-70% of the patients have a mutation in the CREBBP gene (RSTS1) and 5-10% display an EP300 gene mutation (RSTS2). Craniospinal abnormalities such as microcranium, scoliosis, and lordosis are frequent findings in RSTS1, but malformations of the brain or spinal cord are seen only occasionally. Here, we report on a 3-year-old boy with facial abnormalities of RSTS, broad thumbs and halluces, developmental delay, autistic features, cerebellar underdevelopment, and a neural tube defect. Molecular diagnostic of the CREBBP and EP300 genes showed a heterozygous 17-bp deletion (c.5698_5714del AAGGCAGCAGGCCAGGT) in exon 31 of the EP300 gene. Findings underline that small (hypoplastic) cerebellum and neural tube defects belong to the phenotypic spectrum not only of RSTS1 but also of RSTS2. Based on the literature and this observation, we recommend that each individual with RSTS2 should be closely evaluated for neural axis and craniovertebral junction anomalies, and where appropriate, neuroimaging studies should be considered. Our frequency estimate of ~ 6% occult or overt neural tube defects in RSTS2 could represent an underestimate.

中文翻译：

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Rubinstein-Taybi综合征2伴有小脑畸形和神经管畸形。

Rubinstein-Taybi综合征（RSTS）是一种罕见的显性疾病，具有智力残疾，产后生长不足和多种先天性异常。大约50-70％的患者的CREBBP基因突变（RSTS1），而5-10％的患者表现出EP300基因突变（RSTS2）。在RSTS1中经常发现颅骨脊柱异常，例如微头盖骨，脊柱侧凸和脊柱前凸，但仅偶尔可见脑或脊髓畸形。在这里，我们报道了一个3岁男孩，其面部表情为RSTS，拇指和幻觉宽泛，发育迟缓，自闭症特征，小脑发育不足和神经管缺损。CREBBP和EP300基因的分子诊断在EP300基因的外显子31中显示杂合的17 bp缺失（c.5698_5714del AAGGCAGCAGGCCAGGT）。结果表明，小（发育不良的）小脑和神经管缺损不仅属于RSTS1，而且属于RSTS2的表型谱。根据文献和观察结果，我们建议对RSTS2的每个个体都应仔细评估其神经轴和颅脑椎连接异常，并在适当的情况下应考虑进行神经影像学研究。我们对RSTS2中约6％的隐匿或明显神经管缺损的频率估计可能是低估了。