Central precocious puberty

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Central precocious puberty is a condition that causes early sexual development in girls and boys. While puberty normally starts between ages 8 and 13 in girls and between ages 9 and 14 in boys, girls with central precocious puberty begin exhibiting signs before age 8, and boys with this disorder begin before age 9. Signs of puberty include development of pubic and underarm hair, a rapid increase in height (commonly referred to as a "growth spurt"), acne, and underarm odor. Girls also develop breasts and begin their menstrual periods. Boys have growth of the penis and testes and deepening of the voice. Because of the early growth spurt, children with central precocious puberty may be taller than their peers; however, they may stop growing abnormally early. Without proper treatment, some affected individuals are shorter in adulthood compared with other members of their family. Developing ahead of their peers can be emotionally difficult for affected individuals and may lead to psychological and behavioral problems.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

The cause of central precocious puberty is often unknown. The most common known genetic cause of central precocious puberty is mutations in the MKRN3 gene. Changes in other genes are rare causes of the condition, and researchers suspect that changes in genes that have not yet been identified may also be involved in central precocious puberty. The timing of puberty is influenced by several factors in addition to genetics, including nutrition, socioeconomic status, and exposure to certain chemicals in the environment.

The protein produced from the MKRN3 gene plays a role in directing the onset of puberty. Puberty begins when a gland in the brain called the hypothalamus is stimulated to release bursts of a hormone called gonadotropin releasing hormone (GnRH). This hormone triggers the release of other hormones that direct sexual development. Research suggests that the MKRN3 protein blocks (inhibits) the release of GnRH from the hypothalamus, thus holding off the onset of puberty.

The MKRN3 gene mutations involved in central precocious puberty are thought to lead to production of a nonfunctional MKRN3 protein. Although the mechanism is unclear, researchers speculate that without the MKRN3 protein to inhibit GnRH release, the hypothalamus releases bursts of the hormone, which stimulates the onset of puberty earlier than normal.

For most genes, both copies of the gene (one copy inherited from each parent) are active in all cells. However, the activity of the MKRN3 gene depends on which parent it was inherited from. Only the copy inherited from a person's father is active; the copy inherited from the mother is not active. This sort of parent-specific difference in gene activation is caused by a phenomenon called genomic imprinting. Because only the copy of the MKRN3 gene from the father is active, when associated with this gene, the condition can only be inherited from a person's father. Either sons or daughters can have central precocious puberty, although researchers suspect that girls are more severely affected than boys, because the onset of puberty is even earlier than normal in girls than in boys. Boys with an MKRN3 gene mutation inherited from their father may go through puberty at the lower limit of the normal age range, so the condition is not diagnosed.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Central precocious puberty follows an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When passed from parent to child, the condition is known as familial central precocious puberty. In familial cases associated with the MKRN3 gene, the mutation is inherited from the father. In many cases, the father is affected; however, he may be unaffected if he inherited the altered gene from his mother. A father may also be unaffected because some males with a mutation do not show signs of the condition. A father can pass the condition to his sons and daughters.

The condition can also occur in people with no family history of the disorder. These cases are called sporadic central precocious puberty. Some apparently sporadic cases are caused by MKRN3 gene mutations inherited from an unaffected father.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Central precocious puberty is estimated to affect 1 in 5,000 to 10,000 girls. The condition is less common in boys, although the prevalence is unknown.

Which doctor should you see?

The suggested department for discussing Central precocious puberty is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.