Unraveling the Genetic Heterogeneity of Isolated Growth Hormone Deficiency: Insights from the GENHYPOPIT Cohort
Authors' conclusion
Our study broadens the spectrum of genetic variations associated with IGHD. In most cases, the implicated gene is involved in GH secretion, but our results highlight that IGHD can also be caused by genes involved in pituitary development. These findings confirm the importance of genetic analysis in IGHD, to improve patient management and genetic counselling.
Study context
- Population
- Patients with isolated growth hormone deficiency (IGHD) referred for targeted NGS panel analysis through the GENHYPOPIT network, 2017–202423 with P/likely pathogenic (LP) variant
- Participants
- 205 patients
- Outcome
- Genotypes and phenotypes of patients with genetic IGHD
Methodological detailstargeted NGS panel analysis, complementary targeted family analysis, GENHYPOPIT network
- Targeted NGS panel analysis
- Complementary targeted family analysis
- GENHYPOPIT network
Main finding
As reported in the abstract
- Patients with a P or LP variant
- 23 (11.2%)
- Variants in GH secretion genes
- 70%
- Variants in GH1, mostly autosomal dominant transmission
- 39%
- Variants in GHRHR
- 13%
- Variants in GHSR
- 18%
- Variants in pituitary development genes
- 30%
- Variants in GLI2 (most common pituitary development gene; always with pituitary stalk interruption syndrome)
- 13%
- Variants in POU1F1
- 9%
- Variants in HESX1
- 4%
- Variants in SOX3
- 4%
- New P or LP variants reported
- 10
Further findings
Phenotype
- Average age at diagnosis
- 3.9 years
- Pituitary hypoplasia
- 47%
Family analyses
- Family analyses
- 30
- Broadened genotype-phenotype correlation, identified de novo variants and the first reported case of GH1 mosaicism
Original publication
Unraveling the Genetic Heterogeneity of Isolated Growth Hormone Deficiency: Insights from the GENHYPOPIT Cohort. Horm Res Paediatr. Published 29 April 2026. doi:10.
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