Feingold syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Feingold syndrome is a disorder that affects many parts of the body. There are two types of Feingold syndrome, distinguished by their genetic cause; both types have similar features that can vary among affected individuals.

Individuals with Feingold syndrome type 1 or type 2 have characteristic abnormalities of their fingers and toes. Almost all people with this condition have a specific hand abnormality called brachymesophalangy, which refers to shortening of the second and fifth fingers. Other common abnormalities include fifth fingers that curve inward (clinodactyly), underdeveloped thumbs (thumb hypoplasia), and fusion (syndactyly) of the second and third toes or the fourth and fifth toes.

Additional common features of both types of Feingold syndrome include an unusually small head size (microcephaly), a small jaw (micrognathia), a narrow opening of the eyelids (short palpebral fissures), and mild to moderate learning disabilities. Less often, affected individuals have hearing loss, short stature, or kidney or heart abnormalities.

People with Feingold syndrome type 1 are frequently born with a blockage in part of their digestive system called gastrointestinal atresia. In most cases, the blockage occurs in the esophagus (esophageal atresia) or in part of the small intestine (duodenal atresia). Individuals with type 2 do not have gastrointestinal atresias.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the MYCN gene cause Feingold syndrome type 1, and mutations in chromosome 13 that remove (delete) a region of the chromosome that includes the MIR17HG gene cause type 2. Both genes are involved in growth and development, particularly before birth.

The MYCN gene provides instructions for making a protein that regulates the activity (expression) of other genes. The protein attaches (binds) to specific regions of DNA and controls the first step of protein production (transcription). Studies suggest that the MYCN protein is necessary for normal development of the limbs, heart, kidneys, lungs, nervous system, and digestive system.

The MIR17HG gene provides instructions for making a set of microRNAs (miRNAs) known as the miR-17~92 cluster. MiRNAs are short pieces of RNA, a chemical cousin of DNA. These molecules control gene expression by blocking protein production. The miRNAs in the miR-17~92 cluster are involved in the development of many tissues and organs in the body.

Mutations affecting the MYCN or MIR17HG gene that cause Feingold syndrome prevent one copy of the gene in each cell from producing any functional protein or miRNAs, respectively. As a result, only half the normal amount of the protein or miRNAs is available to control the activity of specific genes during development. It remains unclear how a reduced amount of the MYCN protein or miR-17~92 cluster miRNAs cause the specific features of Feingold syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Feingold syndrome appears to be a rare condition, although its exact prevalence is unknown. Type 1 is more common than type 2.

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.

Brachydactyly · Very frequent (99-80%)

Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.

Clinodactyly of the 5th finger · Very frequent (99-80%)

Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).

Deviation of the 2nd finger · Very frequent (99-80%)

Displacement of the 2nd finger from its normal position.

Microcephaly · Very frequent (99-80%)

Head circumference below 2 standard deviations below the mean for age and gender.

Short palpebral fissure · Very frequent (99-80%)

Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures.

Abnormal pinna morphology · Frequent (79-30%)

An abnormality of the pinna, which is also referred to as the auricle or external ear.

Anteverted nares · Frequent (79-30%)

Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).

Depressed nasal bridge · Frequent (79-30%)

Posterior positioning of the nasal root in relation to the overall facial profile for age.

Other findings in the same source

From: Orphanet

Additional reported features include Hallux valgus (Frequent (79-30%)); Intellectual disability (Frequent (79-30%)); Micrognathia (Frequent (79-30%)); Short stature (Frequent (79-30%)); Toe syndactyly (Frequent (79-30%)); Abnormal form of the vertebral bodies (Occasional (29-5%)); Abnormality of the spleen (Occasional (29-5%)); Annular pancreas (Occasional (29-5%)); Duodenal atresia (Occasional (29-5%)); Esophageal atresia (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Feingold 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 Feingold 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.