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Growth and pubertal disorders in neurofibromatosis type 1
R Virdis1, M E Street, M A Bandello
1Dipartimento Età Evolutiva e Materno Infantile, Università di Parma, Italy. ravirdis@unipr.it
Insights
Children with neurofibromatosis type 1 (NF1) experience abnormal growth and puberty patterns, often leading to short stature and delayed menarche. These endocrine complications can increase medical and psychological challenges for affected individuals.
Area of Science:
- Pediatric Endocrinology
- Genetics
- Growth Disorders
Background:
- Neurofibromatosis type 1 (NF1) is associated with endocrine abnormalities, including growth and puberty disturbances.
- Historical observations and recent studies highlight altered height velocity and reduced final adult height in NF1 patients.
- Short stature is a significant concern, with increased prevalence in late puberty and association with severe complications.
Purpose of the Study:
- To investigate the complex patterns of growth and puberty in patients with neurofibromatosis type 1.
- To analyze the incidence of short stature, precocious puberty, and delayed puberty in NF1.
- To understand the implications of these endocrine issues on patient health and well-being.
Main Methods:
- Retrospective analysis of growth data and pubertal development in a cohort of NF1 patients.
- Comparison of growth parameters and pubertal timing with general population data and familial controls.
- Assessment of the association between growth disturbances, puberty, and NF1-related complications.
Main Results:
- NF1 patients exhibit normal growth until puberty, followed by decreased height velocity and relative height.
- A substantial percentage of NF1 patients develop true short stature, with final height below genetic targets.
- Precocious puberty, often linked to optic pathway tumors, and delayed puberty (including delayed menarche) are frequent complications.
Conclusions:
- Growth and puberty follow atypical trajectories in NF1, presenting significant clinical challenges.
- Early identification and management of endocrine dysfunction are crucial for improving outcomes in NF1.
- The interplay between NF1, growth, puberty, and associated medical issues requires further investigation and individualized patient care.
Abstract:
The first textbook of Pediatric Endocrinology in the early 1950s reported an association of neurofibromatosis type 1 (NF1) and precocious puberty (PP) and/or short stature. Recent studies have indicated that children with NF1 grow normally until puberty; thereafter height velocity and relative height (SDS or percentiles) decreases with respect to healthy peers, reaching a mean adult height close to the 25th percentile for the general population. Moreover, the percentage of patients with true short stature (<3rd percentile) increases from childhood (5%) to late puberty (20-30% in literature, 18% in our study), and final height is significantly below the genetic target and predicted adult height calculated just before or at the beginning of puberty. Finally, among the shortest patients (<10th percentile) there is a high incidence of severe complications, such as CNS tumors, huge plexiform neurofibromas and severe scoliosis. Precocious puberty is a frequent complication of NF1, and occurs mainly in association with optic pathway tumors (OPT); however, occasionally it has been reported in the absence of optic gliomas, probably with a similar incidence as in the general population. GnRH agonist therapy must be decided individually as in some patients further growth could be normal and/or treatment would not improve final height. In the presence of early pubertal signs, an OPT must be ruled out. In addition to PP, delayed puberty has been frequently reported in NF1. In a study of 123 girls with NF1, we found that the mean age at menarche (13.0 +/- 1.9 yr) was later than in their mothers (12.7 +/- 1.4 yr) and in the general population (12.4 +/- 1.2 yr; p <0.05), with a very high incidence of delayed menarche (>2 SD): 16% vs 6.8% (mothers) vs 3.4% (controls) (p <0.01). In conclusion, growth and puberty present unusual patterns in NF1, often with true pathological findings increasing medical and psychological problems.