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

Abstract

SUMMARYPrader-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 o f a PWS boy w i t h C P P 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. Arch Endocrinol Metab. 2016;60(6):596-600

Gonadal function and testicular histology in males with Prader‐Willi syndrome

“…Precocious puberty in PWS males is rare, but several cases have been reported in the literature . The mechanism of precocious puberty in PWS is uncertain.…”

“…Precocious puberty in PWS males is rare, but several cases have been reported in the literature. 24,[27][28][29] The mechanism of precocious puberty in PWS is uncertain. It has been reported that the mutation in MKRN3 gene, an imprinted gene located in the PWS critical region (chromosome 15q11-q13) is associate with familial central precocious puberty.…”

The tempo of human childhood: a maternal foot on the accelerator, a paternal foot on the brake

“…As a corollary, effects of imprinted genes on a life-history trait provide strong evidence that the trait has been subject to evolutionary conflicts within the family. Occasional individuals with PWS undergo precocious puberty, 42,43 but most undergo incomplete puberty, expressed as lack of a pubertal growth spurt, hypogonadotropic hypogonadism, cryptorchidism, underdeveloped genitalia, and incomplete menarche. [44][45][46][47][48][49] Thus, other PEGs from this chromosomal region appear to promote, rather than inhibit, aspects of sexual maturation.…”

Premature Adrenarche in Children with Prader-Willi Syndrome Treated with Recombinant Human Growth Hormone Seems to Not Influence the Course of Central Puberty and the Efficacy and Safety of the Therapy

“…Moreover there have been a few cases of central precocious puberty (CPP) in both sexes reported. It can be linked to loss of MKRN3 (makorin RING-finger protein 3) gene, within the 15q11-q13 region, which has been found to be one of the most commonly recognized genetic reason for CPP in the general population [ 17 , 18 , 19 , 20 ]. It has also been reported that premature adrenarche (PA) can be present in a significant part of PWS patients [ 21 , 22 , 23 ].…”