Goel Himanshu, Harrison Katrina
Genomic Health, West Leederville, Western Australia, Australia.
Hunter Genetics, Waratah, New South Wales, Australia.
Mol Genet Genomic Med. 2025 Sep;13(9):e70136. doi: 10.1002/mgg3.70136.
Culler-Jones syndrome (CJS) is an autosomal dominant disorder characterized by hypopituitarism, postaxial polydactyly, and craniofacial anomalies, associated with pathogenic GLI2 variants. Genotype-phenotype correlations suggest missense variants may present with isolated pituitary phenotypes.
We evaluated an 8-year-old boy referred for short stature, failure to thrive, and neurodevelopmental concerns. Clinical assessment, endocrine evaluation, imaging studies, and trio exome sequencing were performed.
The patient exhibited growth hormone deficiency, dolichocephaly, midline diastema, lip and tongue ties, hypotonia, and ADHD. No polydactyly was noted. Trio exome sequencing revealed a de novo heterozygous likely pathogenic GLI2 variant (c.1496G>T; p.Arg499Leu) located within the DNA-binding zinc finger domain.
This case expands the phenotypic spectrum of GLI2-related disorders and reinforces that non-truncating GLI2 variants are often associated with isolated hypopituitarism and subtle craniofacial or neurodevelopmental features. Genomic testing should be considered in similar clinical presentations.
卡勒-琼斯综合征（CJS）是一种常染色体显性疾病，其特征为垂体功能减退、轴后多指畸形和颅面畸形，与致病性GLI2变异相关。基因型-表型相关性提示错义变异可能表现为孤立性垂体表型。
我们评估了一名8岁男孩，他因身材矮小、生长发育不良和神经发育问题前来就诊。进行了临床评估、内分泌评估、影像学检查和三联体外显子组测序。
该患者表现出生长激素缺乏、长头畸形、中线间隙、唇系带和舌系带、肌张力减退和注意力缺陷多动障碍。未发现多指畸形。三联体外显子组测序发现一个位于DNA结合锌指结构域内的新生杂合可能致病性GLI2变异（c.1496G>T；p.Arg499Leu）。
该病例扩展了GLI2相关疾病的表型谱，并强化了非截短型GLI2变异通常与孤立性垂体功能减退以及细微的颅面或神经发育特征相关的观点。对于类似临床表现应考虑进行基因组检测。
