Costello syndrome is a rare genetic disorder associated with developmental delay, short stature, and pubertal delay. However, a few cases of precocious puberty have been reported, reflecting the complex regulation of the hypothalamic-pituitary-gonadal axis affected by Harvey rat sarcoma viral oncogene homolog (HRAS) gene mutations. We present a case of a boy with Costello syndrome, heterozygous for a mutation in the HRAS gene, first seen in a pediatric endocrinology consultation at the age of nine years and seven months with central precocious puberty and short stature (-0.61 SD). The growth rate had accelerated from age seven years and six months. Pubarche and testicular enlargement began at age eight, and by nine years and seven months, the patient had reached Tanner stage V, with a testicular volume of 20 ml. Bone age was estimated to be 13 years. The brain magnetic resonance imaging (MRI) identified a Chiari type I malformation. At nine years and eight months, triptorelin treatment was initiated, leading to a reduction of pubic hair, stabilization of testicular volume, and a stature of -1.64 SD at the age of 13 years. Despite known factors influencing puberty, the precise physiological mechanisms behind its initiation remain unclear. This case provides valuable insights for understanding the genotype-phenotype relationship in Costello syndrome.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873749PMC
http://dx.doi.org/10.7759/cureus.78321DOI Listing

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An Unusual Presentation of Costello Syndrome in a Boy with Precocious Puberty and Chiari I Malformation: A Case Report.

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February 2025

Pediatric Endocrinology and Diabetology Unit, Pediatrics Department, Unidade Local de Saúde de Braga, Braga, PRT.

Costello syndrome is a rare genetic disorder associated with developmental delay, short stature, and pubertal delay. However, a few cases of precocious puberty have been reported, reflecting the complex regulation of the hypothalamic-pituitary-gonadal axis affected by Harvey rat sarcoma viral oncogene homolog (HRAS) gene mutations. We present a case of a boy with Costello syndrome, heterozygous for a mutation in the HRAS gene, first seen in a pediatric endocrinology consultation at the age of nine years and seven months with central precocious puberty and short stature (-0.

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