Genetic factors play a crucial role in determining human height. Short stature commonly affects multiple family members and therefore, familial short stature (FSS) represents a significant proportion of growth disorders. Traditionally, FSS was considered a benign polygenic condition representing a subcategory of idiopathic short stature (ISS). However, advancements in genetic research have revealed that FSS can also be monogenic, inherited in an autosomal dominant manner and can result from different mechanisms including primary growth plate disorders, growth hormone deficiency/insensitivity or by the disruption of fundamental intracellular pathways. These discoveries have highlighted a broader phenotypic spectrum for monogenic forms of short stature, which may exhibit mild manifestations indistinguishable from ISS. Given the overlapping features and the difficulty in differentiating polygenic from monogenic FSS without genetic testing, some researchers redefine FSS as a descriptive term that encompasses any familial occurrence of short stature, regardless of the underlying cause. This shift emphasizes the complexity of diagnosing and managing short stature within families, reflecting the diverse genetic landscape that influences human growth.

• Klíčová slova
• autosomal dominant short stature, familial short stature, genetics, growth plate, short stature,
• MeSH
• fenotyp MeSH
• lidé MeSH
• nanismus genetika   MeSH
• poruchy růstu * genetika   MeSH
• tělesná výška * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Because the causes of combined pituitary hormone deficiency (CPHD) are complex, the etiology of congenital CPHD remains unknown in most cases. The aim of the study was to identify the genetic etiology of CPHD in a well-defined single-center cohort. In total, 34 children (12 girls) with congenital CPHD (growth hormone (GH) deficiency and impaired secretion of at least one other pituitary hormone) treated with GH in our center were enrolled in the study. Their median age was 11.2 years, pre-treatment height was -3.2 s.d., and maximal stimulated GH was 1.4 ug/L. Of them, 30 had central adrenal insufficiency, 27 had central hypothyroidism, ten had hypogonadotropic hypogonadism, and three had central diabetes insipidus. Twenty-six children had a midline defect on MRI. Children with clinical suspicion of a specific genetic disorder underwent genetic examination of the gene(s) of interest via Sanger sequencing or array comparative genomic hybridization. Children without a detected causal variant after the first-tier testing or with no suspicion of a specific genetic disorder were subsequently examined using next-generation sequencing growth panel. Variants were evaluated by the American College of Medical Genetics standards. Genetic etiology was confirmed in 7/34 (21%) children. Chromosomal aberrations were found in one child (14q microdeletion involving the OTX2 gene). The remaining 6 children had causative genetic variants in the GLI2, PROP1, POU1F1, TBX3, PMM2, and GNAO1 genes, respectively. We elucidated the cause of CPHD in a fifth of the patients. Moreover, our study supports the PMM2 gene as a candidate gene for CPHD and suggests pathogenic variants in the GNAO1 gene as a potential novel genetic cause of CPHD.

• Klíčová slova
• combined pituitary hormone deficiency, genetics of short stature, growth hormone deficiency, next-generation sequencing, short stature,
• Publikační typ
• časopisecké články MeSH