Syndromic failure to thrive and short stature in children: Genetic mechanisms, endocrine implications, and responses to nutritional and growth hormone therapies

Short stature and failure to thrive (FTT) are indicative of a number of congenital syndromes. Numerous factors such as malnutrition, endocrine dysfunction and structural or genetic abnormalities, can cause these growth disturbances. Although GH therapy and nutritional interventions have been investigated for a number of syndromes, their effectiveness varies according to the pathophysiology that underlies them.

Objectives: The objectives of this mini-review are to: (1) characterize the growth characteristics and endocrine abnormalities linked to specific genetic syndromes that manifest as short stature or FTT (2) assess the efficacy of GH therapy and nutritional support and (3) evaluate the prognosis and outcomes across syndromic categories.

Methods: We included studies released between 2000 and 2024. A systematic literature review was carried out using PubMed, Scopus, and Embase. Studies that reported on endocrine profiles, clinical growth parameters, and treatment outcomes in syndromic FTT were required to meet inclusion criteria. Growth features, GH response, nutritional impact, and long-term prognosis were all described.

Results: A total of ten syndromes were examined. There was widespread endocrine dysfunction such as GH resistance or deficiency (e. g. A. IGF-1 axis abnormalities (e. g. Turner syndrome, Russell-Silver syndrome), hypothyroidism (e. g. Noonan syndrome,  Seckel syndrome, Down syndrome, and hypogonadism (e. g. Prader–Willi syndrome. In cases where malabsorption or feeding issues predominated, such as Rett syndrome, CHARGE, and cystic fibrosis, nutritional rehabilitation produced notable growth benefits. Height SDS improved with GH therapy in several conditions. The most consistent positive response was seen in 3-M syndrome, Turner syndrome, Prader-Willi syndrome, and Noonan syndrome (PTPN11-negative). However, in Cornelia de Lange Rett and Seckel syndromes, GH therapy had little effect, most likely because of underlying structural or neurodevelopmental barriers. Early diagnosis, interdisciplinary treatment, and customized dietary and endocrine therapies all improved the prognosis.

Conclusion: In summary, growth failure and syndromic FTT have a variety of endocrine and nutritional causes. In certain situations, targeted interventions, particularly early GH treatment and all-encompassing nutritional support, can greatly enhance growth and developmental outcomes. In order to maximize response and direct clinical care, a syndrome-specific approach is necessary.