ANE syndrome

What it is

From: Orphanet

A rare, genetic, neuro-endocrino-cutaneous disorder characterized by highly variable degrees of alopecia, moderate to severe intellectual disability, progressive, late-onset motor deterioration and combined anterior pituitary hormone deficiency, manifesting with central hypogonadotropic hypogonadism, delayed or absent puberty, growth hormone deficiency (resulting in short stature), progressive central adrenal insufficiency and a hypoplastic anterior pituitary gland. Additional features include hypodontia, flexural reticulate hyperpigmentation, gynecomastia, microcephaly and kyphoscoliosis.

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.

Abnormal response to ACTH stimulation test · Frequent (79-30%)

An anomalous response to stimulation by administration of the adrenocorticotropic hormone (ACTH). ACTH stimulation normally stimulates the adrenal glands to release cortisol and adrenaline.

Adrenocorticotropin deficient adrenal insufficiency · Frequent (79-30%)

Adrenal insufficiency secondary to a defect in ACTH production.

Alopecia · Frequent (79-30%)

A noncongenital process of hair loss, which may progress to partial or complete baldness.

Anterior pituitary hypoplasia · Frequent (79-30%)

Underdevelopment of the anterior pituitary gland.

Carious teeth · Frequent (79-30%)

Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.

Decreased response to growth hormone stimulation test · Frequent (79-30%)

Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.

Decreased serum insulin-like growth factor 1 · Frequent (79-30%)

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

Delayed puberty · Frequent (79-30%)

Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.

Delayed skeletal maturation · Frequent (79-30%)

A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.

Gynecomastia · Frequent (79-30%)

Abnormal development of large mammary glands in males resulting in breast enlargement.

Hyperpigmentation of the skin · Frequent (79-30%)

A darkening of the skin related to an increase in melanin production and deposition.

Hypodontia · Frequent (79-30%)

The absence of five or less teeth from the normal series by a failure to develop.

Hypogonadotropic hypogonadism · Frequent (79-30%)

Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones: follicle stimulating hormone (FSH) and luteinizing hormone (LH).

Intellectual disability · Frequent (79-30%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Other findings in the same source

From: Orphanet

Additional reported features include Kyphoscoliosis (Frequent (79-30%)); Lipoatrophy (Frequent (79-30%)); Microcephaly (Frequent (79-30%)); Motor deterioration (Frequent (79-30%)); Motor neuron atrophy (Frequent (79-30%)); Premature loss of teeth (Frequent (79-30%)); Short stature (Frequent (79-30%)); Ulnar deviation of the hand (Frequent (79-30%)); Decreased serum testosterone concentration (Frequent (79-30%)); Hyperpigmented nevi (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adult

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Reported case(s): 5.0; 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 recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing ANE syndrome 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

The material gathered for this draft does not provide a complete condition-specific treatment pathway for ANE syndrome. 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.