Beyond GH stimulation tests: genetic heterogeneity and treatment response in children with diagnosed GH…

Cohort studyJournal of the Endocrine Society· Jun 2026

Beyond GH stimulation tests: genetic heterogeneity and treatment response in children with diagnosed GH deficiency.

Lukas Plachy, Petra Dusatkova, Lukas Kavciak … Stepanka Pruhova

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Clinical GeneticsCohort studyQ2IF 3.1

A genetic cause was identified in 17% of children with clinically diagnosed growth hormone deficiency.

Beyond GH stimulation tests: genetic heterogeneity and treatment response in children with diagnosed GH deficiency.

Lukas Plachy … Stepanka Pruhova

Journal of the Endocrine Society · Jun 2026

Background

Growth hormone (growth hormone) stimulation tests have limited reliability and may lead to false-positive results.

Purpose

This work aimed to evaluate genetic causes of short stature in children clinically diagnosed with growth hormone deficiency (GH deficiency) and assess genotype-phenotype correlations.

Methods

A retrospective single-center study was conducted including 233 children with clinically diagnosed primary growth hormone deficiency treated with growth hormone for 5 years or more.

n = 233 children

17%

Results

17%

Genetic testing found a causative variant in 39 of 233 children thought to have growth hormone deficiency.

n = 233 children

More results

Only 13 of 39 (33%) findings confirmed GH deficiency (genes CHD7 , GH1, GHSR , GLI2 , GNAO1 , KMT2D , OTX2 [3], POU1F1 , PROP1 , SALL4 , TBX3 ).

More results

The remaining 26 of 39 (67%) revealed alternative etiologies of growth failure: RASopathies (13/39; genes NF1 [2], PTPN11 [7], RAF1 , SOS1 [2], SPRED1 ), growth plate disorders (8/39; genes ACAN , COL2A1 , EXT2 , FGFR3 [2], NPR2 [3]), and miscellaneous conditions (5/39; genes CDC42 , LMNA , HMGA2 , PMM2 , RAI1 ).

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Conclusion · 1 of 2

The population of children clinically diagnosed with GH deficiency is genetically heterogeneous.

Conclusion · 2 of 2

A statistically significant proportion harbors defects in RAS-MAPK signaling or growth plate disorders, highlighting the limitations of current methods of GH deficiency diagnostics.

Beyond GH stimulation tests: genetic heterogeneity and treatment response in children with diagnosed GH deficiency.

Beyond GH stimulation tests: genetic heterogeneity and treatment response in children with diagnosed GH deficiency.

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