X-linked acrogigantism

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

X-linked acrogigantism (X-LAG) is a condition that causes abnormally fast growth beginning early in life. Babies with this condition are a normal size at birth but begin to grow rapidly in infancy or early childhood, and affected children are taller than their peers.

This rapid growth is caused by an abnormality of the pituitary gland. The pituitary gland, which is found at the base of the brain, produces hormones that control many important body functions, including growth. Individuals with X-LAG may have the condition as a result of enlargement (hyperplasia) of the gland or development of a noncancerous tumor in the gland (called a pituitary neuroendocrine tumor or PitNET). Rarely, an affected individual has both pituitary hyperplasia and a pituitary neuroendocrine tumor. The abnormal gland releases excess amounts of growth hormone, a hormone that normally helps direct growth of the body's bones and tissues. The abnormal gland can also release excess amounts of another hormone called prolactin, which helps control the function of the internal reproductive organs (gonads).

Some people with X-LAG have additional signs and symptoms such as facial features that are described as coarse; disproportionately large hands or feet (acral enlargement); an increased appetite; and a skin condition called acanthosis nigricans, in which the skin in body folds and creases becomes thick, dark, and velvety.

ORPHANET DEFINITION A rare, genetic pituitary disease characterized by infantile-onset, rapid and excessive acceleration of linear growth and body size due to mixed growth hormone (GH)- and prolactin-secreting adenomas and/or pituitary hyperplasia. Patients present with gigantism and may have associated acromegalic features (e.g. coarse facial features, frontal bossing, prognathism, increased interdental space) as well as marked enlargement of hands and feet, soft tissue swelling, increased appetite and acanthosis nigricans.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

Autosomal dominant

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 33.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of the pituitary gland · Very frequent (99-80%)

An anomaly of the pituitary gland.

Elevated circulating growth hormone concentration · Very frequent (99-80%)

Acromegaly is a condition resulting from overproduction of growth hormone by the pituitary gland in persons with closed epiphyses, and consists chiefly in the enlargement of the distal parts of the body. The circumference of the skull increases, the nose becomes broad, the tongue becomes enlarged, the facial features become coarsened, the mandible grows excessively, and the teeth become separated. The fingers and toes grow chiefly in thickness.

Increased circulating insulin-like growth factor 1 concentration · Very frequent (99-80%)

The concentration of insulin-like growth factor 1 (IGF1) in the blood circulation is above the upper limit of normal.

Increased circulating prolactin concentration · Very frequent (99-80%)

The presence of abnormally increased levels of prolactin in the blood. Prolactin is a peptide hormone produced by the anterior pituitary gland that plays a role in breast development and lactation during pregnancy.

Tall stature · Very frequent (99-80%)

A height above that which is expected according to age and gender norms.

Abnormal oral glucose tolerance · Frequent (79-30%)

An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral administration of glucose.

Abnormality of optic chiasm morphology · Frequent (79-30%)

A structural abnormality of the optic chiasm.The optic chiasm, located below the hypothalamus, is a partial crossing of the optic nerves.

Coarse facial features · Frequent (79-30%)

Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

Decreased thyroid-stimulating hormone level · Frequent (79-30%)

Reduced amount of the thyroid-stimulating hormone (TSH), which is produced by the anterior pituitary gland and stimulates the function of the thyroid gland.

Fasting hyperinsulinemia · Frequent (79-30%)

An increased concentration of insulin in the blood in the fasting state, i.e., not as the response to food intake.

Hyperhidrosis · Frequent (79-30%)

Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.

Increased body mass index · Frequent (79-30%)

Abnormally increased weight-to-height squared ratio, calculated by dividing the individual's weight in kilograms by the square of the individual's height in meters and used as an indicator of overweight compared to averages.

Pituitary adenoma · Frequent (79-30%)

A benign epithelial tumor derived from intrinsic cells of the adenohypophysis (anterior pituitary).

Polyphagia · Frequent (79-30%)

A neurological anomaly with gross overeating associated with an abnormally strong desire or need to eat.

Other findings in the same source

From: Orphanet

Additional reported features include Sleep apnea (Frequent (79-30%)); Snoring (Frequent (79-30%)); Thickened skin (Frequent (79-30%)); Abdominal distention (Occasional (29-5%)); Abnormality of the cardiovascular system (Occasional (29-5%)); Abnormality of the skeletal system (Occasional (29-5%)); Acanthosis nigricans (Occasional (29-5%)); Adrenocorticotropic hormone deficiency (Occasional (29-5%)); Ataxia (Occasional (29-5%)); Delayed puberty (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Childhood; Infancy; Neonatal

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

Autosomal dominant

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Reported case(s): 33.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal dominant pattern means that one altered copy of a relevant gene can be sufficient for the condition. Some affected people inherit the change; others have a new change without an affected parent. The precise finding, family history and condition determine what this means for relatives.

Which doctor should you see?

The suggested department for discussing X-linked acrogigantism is Endocrinology, with a endocrinologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

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.

• Which hormone or metabolic finding is important in this case?
• How should test timing and current medicines be taken into account?
• What follow-up would show whether the care plan is working?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for X-linked acrogigantism. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

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.