Neurofibromatosis Type 1 and Precocious Puberty

Abstract

Since neurofibromatosis type 1 (NF1) is a well known cause of precocious puberty (PP), we reviewed 412 NF1 pediatric patients to evaluate the prevalence of PP, the association with optic pathway tumors (OPT), and other clinical, auxological and hormonal data. Thirty-one of 412 patients had OPT (7.5%), 10/412 PP (2.4%), and in seven of these PP was associated with OPT (7/31, 22.6%). OPT in patients with PP involved the chiasm in four patients, and the optic nerves alone in three patients. The age at the onset of puberty (or better at diagnosis) ranged from 5.2 to 7.5 yr in girls (n=6) and from 7.9 to 8.9 yr in boys (n=4). LHRH agonist therapy was used in only three children because in the others the predicted height at diagnosis was good, treatment was refused or the patients were referred to us too late. The three treated patients attained a final height within the familial range. In the untreated patients the progression of puberty was not too rapid and final height was slightly below the genetic target in four patients; however, three patients had a final height markedly below the familial range. In conclusion, the prevalence of PP is increased in children with NF1, and frequently but not exclusively is associated with OPT. Moreover, sexual precocity does not seem to be necessarily bound to chiasmatic OPT. Treatment seems to be useful in the children with younger age at the onset of puberty or with a progressive decline in predicted final height.

Silver-Russell Syndrome-like Features in a Patient Carrying a Novel NF1 Mutation

“…Thereafter, height velocity and relative height (standard deviation scores or percentiles) decrease 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 (lower than the third percentile) increases from childhood (5%) to late puberty (18%), and final height is significantly below the genetic target and predicted adult height calculated just before or at the beginning of puberty (20). These clinical data suggest that alterations of stature in NF1 are the result of lower growth velocity during adolescence.…”

Endocrine Problems in Children with Neurofibromatosis Type 1

“…Santral erken ergenlik sıklığı NF-1 hastalarında %3 civarında olup, genel populasyondan 4 kat fazladır (3,4). Erken ergenlik ve NF-1 ile ilgili birçok vaka serisi yayınlanmıştır.…”

“…Çoğu NF-1 hastasında ise, normal pubertal gidiş görülmekle birlikte literatürde gecikmiş püberte olguları rapor edilmiş ancak tam olarak sıklığı belirtilmemiştir. NF-1 ile birlikte gecikmiş menarş erken püberteden daha sıktır ve başlıca pubertal sorun olduğu vurgulanmıştır (2,3). İki olgumuzda boy kısalığı ve kilo azlığı ile birlikte yapısal ergenlik gecikmesi gözlenmiştir.…”

“…İntrakraniyel yerleşimli suprasellar lezyonlara bağlı santral hipotiroidi ve büyüme hormonu eksikliği de gözlenebil-mektedir. Bazı erken ergenlik ve büyüme hormonu eksikliği gös-teren olgularda optik kiazma gliomaları da rapor edilmiştir (1)(2)(3)(4)(5).…”

Reproductive disturbances in multiple neuroendocrine tumor syndromes

“…Central activation of pituitary gonadotrope function, mostly, but not solely, due to the presence of optic pathway tumors or hypothalamic involvement, may induce central precocious puberty in young NF1 patients. In NF1, precocious puberty has been reported in 2.4% of the patients, while delayed puberty may also occur (Carmi et al 1999, Virdis et al 2000.…”