The relationship between congenital defects of the brain and facial anomalies was proven. The Hedgehog signaling pathway plays a fundamental role in normal craniofacial development in humans. Mutations in the sonic hedgehog (SHH) signaling gene CDON have been recently reported in patients with holoprosencephaly and with pituitary stalk interruption syndrome (PSIS). This study’s aim was an elucidation of an 18-year-old patient presenting PSIS, multiple pituitary hormone deficiency, and congenital unilateral facial and abducens nerve palsy. Additionally, bilateral sensorineural hearing loss, dominating at the right site, was diagnosed. From the second year of life, growth deceleration was observed, and from the age of eight, anterior pituitary hormone deficiencies were gradually confirmed and substituted. At the MRI, characteristic triad for PSIS (anterior pituitary hypoplasia, interrupted pituitary stalk and ectopic posterior lobe) was diagnosed. We performed a comprehensive genomic screening, including microarrays for structural rearrangements and whole-exome sequencing for a monogenic defect. A novel heterozygous missense variant in the CDON gene (c.1814G > T; p.Gly605Val) was identified. The variant was inherited from the mother, who, besides short stature, did not show any disease symptoms. The variant was absent in control databases and 100 healthy subjects originating from the same population. We report a novel variant in the CDON gene associated with PSIS and congenital cranial nerve palsy. The variant revealed autosomal dominant inheritance with incomplete penetrance in concordance with previous studies reporting CDON defects.

大脑先天性缺陷与面部异常之间的关系已得到证实。 Hedgehog 信号通路在人类正常颅面发育中发挥着重要作用。最近报道了前脑无裂畸形和垂体柄中断综合征 (PSIS) 患者中音刺猬 (SHH) 信号基因CDON 的突变。本研究的目的是阐明一名 18 岁患者患有 PSIS、多种垂体激素缺乏症以及先天性单侧面部和外展神经麻痹。此外，还诊断出双侧感音神经性听力损失，主要发生在右侧部位。从出生第二年起，观察到生长减慢，从八岁起，垂体前叶激素缺乏逐渐得到证实和替代。 MRI 诊断出 PSIS 的特征性三联征（垂体前叶发育不全、垂体柄中断和异位后叶）。我们进行了全面的基因组筛查，包括用于结构重排的微阵列和用于单基因缺陷的全外显子组测序。鉴定出CDON基因中的一个新的杂合错义变体（c.1814G > T；p.Gly605Val）。该变异遗传自母亲，母亲除了身材矮小外，没有表现出任何疾病症状。对照数据库和来自同一人群的 100 名健康受试者中不存在该变体。我们报告了与 PSIS 和先天性颅神经麻痹相关的CDON基因的新变异。该变异揭示了具有不完全外显率的常染色体显性遗传，与之前报告CDON缺陷的研究一致。