Gorlin-Chaudhry-Moss syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Gorlin-Chaudhry-Moss syndrome is a condition that affects many parts of the body. The signs and symptoms of this disorder are apparent from birth or infancy.

Gorlin-Chaudhry-Moss syndrome is characterized by the premature closure of certain bones of the skull (craniosynostosis) during development, which affects the shape of the head and face. Many people with this disorder have a premature fusion of skull bones along the coronal suture, the growth line that goes over the head from ear to ear. These changes can result in a head that is abnormally wide and pointed at the top (acrobrachycephaly). Affected individuals also have distinctive facial characteristics that can include a flat or sunken appearance of the middle of the face (midface hypoplasia), and small eyes (microphthalmia) with narrowed openings (narrowed palpebral fissures). Affected individuals may also have farsightedness (hyperopia) and dental problems such as small teeth (microdontia) or fewer teeth than normal (hypodontia).

Many people with Gorlin-Chaudhry-Moss syndrome have a lack of fatty tissue under the skin (lipodystrophy). The lack of fat, together with thin, wrinkled, loose skin and veins visible beneath the skin, makes affected individuals look older than their biological age. This appearance of premature aging is sometimes described as progeroid.

Affected individuals also have excessive hair growth (hypertrichosis) on their face and body. They have a low hairline on the forehead and their scalp hair is often coarse. People with Gorlin-Chaudhry-Moss syndrome also have shortened bones at the ends of the fingers and toes (short distal phalanges). Affected females have unusually small external genital folds (hypoplasia of the labia majora).

Some individuals with Gorlin-Chaudhry-Moss syndrome have mild developmental delay but intelligence is usually normal in this disorder, as is life expectancy.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Gorlin-Chaudhry-Moss syndrome can be caused by mutations in the SLC25A24 gene. This gene provides instructions for producing a protein that transports molecules across the inner membrane of the mitochondria, the energy-producing centers in cells. Among these molecules is ATP, which is the cell's main energy source. Transportation of ATP within the mitochondria is essential for normal energy production, the formation and breakdown (metabolism) of various molecules, and protein production within cells.

The mutations that cause Gorlin-Chaudhry-Moss syndrome are thought to alter the structure of the protein produced from the SLC25A24 gene, which likely decreases its ability to transport molecules across the mitochondrial inner membrane. As a result, there is an increase in mitochondrial size (mitochondria swelling), breakage of mitochondria into smaller pieces, and an overall decrease in energy production. This increase in abnormal mitochondria and decrease in cellular energy can lead to cell death. While altered cellular energy production and increased cell death are likely responsible for the features of Gorlin-Chaudhry-Moss syndrome, it is unclear how these changes lead to the specific signs and symptoms of the condition.

In some affected individuals, no mutation in the SLC25A24 gene has been found. Changes in other unknown genes may cause the disorder in these cases.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

In individuals with an SLC25A24 gene mutation, Gorlin-Chaudhry-Moss syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, the condition results from new (de novo) mutations in the gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development.

Since all known individuals with Gorlin-Chaudhry-Moss syndrome have been female, there are likely other unknown, sex-related factors involved in the inheritance of this condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Gorlin-Chaudhry-Moss syndrome is an extremely rare condition. Approximately ten affected individuals have been described in the medical literature. All known individuals with this condition have been female.

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 eyelid morphology · Very frequent (99-80%)

An abnormality of the eyelids.

Abnormal foot morphology · Very frequent (99-80%)

An abnormality of the skeleton of foot.

Abnormal metacarpal morphology · Very frequent (99-80%)

Any abnormal shape or structure of the metacarpal bones.

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

Any abnormality of the teeth.

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

Any abnormality of the eye, including location, spacing, and intraocular abnormalities.

Abnormality of vision · Very frequent (99-80%)

Abnormality of eyesight (visual perception).

Brachycephaly · Very frequent (99-80%)

An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.

Coarse hair · Very frequent (99-80%)

Hair shafts are rough in texture.

Other findings in the same source

From: Orphanet

Additional reported features include Conductive hearing impairment (Very frequent (99-80%)); Coronal craniosynostosis (Very frequent (99-80%)); Generalized hirsutism (Very frequent (99-80%)); Hypertelorism (Very frequent (99-80%)); Low anterior hairline (Very frequent (99-80%)); Nystagmus (Very frequent (99-80%)); Oligodontia (Very frequent (99-80%)); Short distal phalanx of finger (Very frequent (99-80%)); Short stature (Very frequent (99-80%)); Underdeveloped supraorbital ridges (Very frequent (99-80%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Gorlin-Chaudhry-Moss syndrome is Rheumatology, with a rheumatologist 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.

• Are the findings inflammatory, structural or due to another mechanism?
• Is there evidence that other organs need assessment?
• How will function and any treatment-related risks be monitored?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Gorlin-Chaudhry-Moss 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.