A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy.

Natasha G. Ludwig,Rafael F. Radaeli,Delanie B. Macedo,Maria L. Oliveira,Alexandre J. F. Carrilho,Tânia L. Mazzuco,Danielle Bessa,Camila M. Romero,Ana Claudia Latronico,Mariana M. X. Silva

doi:10.1590/2359-3997000000196

Abstract

Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

Highlights

Prader-Willi syndrome (PWS), known as Prader-Labhart-Willi syndrome, is a complex neurogenetic disorder characterized by neonatal hypotonia, psychomotor delay, early-onset hyperphagia, short stature, hypogonadism, sleep disturbance, learning disabilities, and behavioral and psychiatric disorders; it represents the most common form of genetic obesity
Patients with PWS have multiple characteristics associated with hypothalamic dysfunctions, such as hyperphagia, growth hormone (GH) deficiency, and abnormal pubertal development [1]
These patients have hypogonadism manifested as genital hypoplasia and unilateral or bilateral cryptorchidism, incomplete pubertal development, and infertility, which are attributed to both hypothalamic dysfunction and/or to primary gonadal defect [4]

Summary

Introduction

Prader-Willi syndrome (PWS), known as Prader-Labhart-Willi syndrome, is a complex neurogenetic disorder characterized by neonatal hypotonia, psychomotor delay, early-onset hyperphagia, short stature, hypogonadism, sleep disturbance, learning disabilities, and behavioral and psychiatric disorders; it represents the most common form of genetic obesity. Patients with PWS have multiple characteristics associated with hypothalamic dysfunctions, such as hyperphagia, growth hormone (GH) deficiency, and abnormal pubertal development [1]. These patients have hypogonadism manifested as genital hypoplasia and unilateral or bilateral cryptorchidism, incomplete pubertal development, and infertility, which are attributed to both hypothalamic dysfunction and/or to primary gonadal defect [4]. Hypogonadism is one of the eight major clinical diagnostic signs of PWS, whereas isolated premature adrenarche is frequently observed and is accepted as a minor criterion [3]

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