Familial male precocious puberty

Familial Male Precocious Puberty

Familial Male Precocious Puberty (FMPP), also known as testotoxicosis, is a rare genetic disorder characterized by early onset of puberty in males. This condition is caused by mutations in the luteinizing hormone receptor (LHCGR) gene, leading to autonomous testosterone production independent of luteinizing hormone (LH) stimulation.

Pathophysiology

FMPP is an autosomal dominant disorder, meaning that a single copy of the mutated gene can cause the condition. The mutation in the LHCGR gene results in constitutive activation of the receptor, which stimulates the testes to produce testosterone without the need for LH. This leads to early development of secondary sexual characteristics in affected boys, typically before the age of 9.

Clinical Presentation

Boys with FMPP exhibit signs of puberty much earlier than their peers. Common clinical features include:

• Accelerated growth and bone maturation
• Early development of pubic and axillary hair
• Increased muscle mass
• Deepening of the voice
• Acne
• Advanced bone age, which can lead to early epiphyseal closure and reduced adult height

Diagnosis

Diagnosis of FMPP is based on clinical presentation, family history, and genetic testing. Elevated levels of testosterone with low or normal LH levels are indicative of the condition. Genetic testing can confirm the presence of mutations in the LHCGR gene.

Management

The primary goal of treatment is to manage symptoms and prevent early epiphyseal closure to maximize adult height. Treatment options include:

• Anti-androgens: Medications such as spironolactone or bicalutamide can block the effects of testosterone.
• Aromatase inhibitors: These drugs, such as anastrozole or letrozole, can prevent the conversion of testosterone to estrogen, slowing bone maturation.
• GnRH analogs: Although not directly effective in FMPP, they may be used in combination with other treatments to manage symptoms.

Prognosis

With appropriate management, individuals with FMPP can achieve a normal adult height and lead a healthy life. However, untreated FMPP can result in short stature due to early closure of growth plates.

Genetic Counseling

Since FMPP is an autosomal dominant condition, genetic counseling is recommended for affected families. Parents of a child with FMPP have a 50% chance of passing the mutation to their offspring.

Research Directions

Ongoing research aims to better understand the molecular mechanisms of FMPP and develop more targeted therapies. Advances in genetic testing and personalized medicine hold promise for improved management of this condition.

Also see

• Precocious puberty
• Luteinizing hormone
• Endocrinology
• Genetic disorders