Gorlin Chaudhry Moss syndrome

Other Names: Craniofacial dysostosis, patent ductus arteriosus, hypertrichosis, hypoplasia of labia majora, dental and eye anomalies; GCM syndrome; Gorlin-Chaudhry-Moss syndrome

Definition

Gorlin-Chaudhry-Moss (GCM) syndrome is a multiple congenital anomaly syndrome characterized by craniofacial dysostosis, facial dysmorphism, conductive hearing loss, generalized hypertrichosis, and extremity, ocular and dental anomalies.

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).

Cause

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.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

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.

Epidemiology

To date, 7 cases of GCM have been described in the world literature and all patients are female with no known parental consanguinity.

Similar diseases

Progeroid syndrome, Petty type and Saethre-Chotzen syndrome (see these terms) have overlapping features with GCM syndrome and should be considered in the differential diagnosis.

Etiology

The etiology is still unknown and, to date, no causative gene has been implicated in the physiopathology of GCM.

Symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormality of the foot(Abnormal feet morphology)
• Abnormality of the metacarpal bones(Abnormality of the long bone of hand)
• Abnormality of vision(Abnormality of sight)
• Brachycephaly(Short and broad skull)
• Coarse hair(Coarse hair texture)
• Conductive hearing impairment(Conductive deafness)
• Congenital craniofacial dysostosis
• Coronal craniosynostosis
• Generalized hirsutism(Excessive hairiness over body)
• Hypertelorism(Wide-set eyes)
• Low anterior hairline(Low frontal hairline)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Oligodontia(Failure of development of more than six teeth)
• Short distal phalanx of finger(Short outermost finger bone)
• Short stature(Decreased body height)
• Underdeveloped supraorbital ridges(Flattened bony protrusion above eyes)

30%-79% of people have these symptoms

• Aplasia/Hypoplasia of the nasal bone
• Astigmatism
• Abnormal curving of the cornea or lens of the eye
• Hypoplasia of the maxilla(Decreased size of maxilla)
• Patent ductus arteriosus
• Sclerocornea(Hardening of skin and connective tissue)
• Umbilical hernia

5%-29% of people have these symptoms

• Intellectual disability, mild(Mental retardation, borderline-mild)
• Upper eyelid coloboma(Cleft upper eyelid)

Treatment

The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Ibuprofen lysine (Brand name: NeoProfen®)For closure of a clinically significant patent ductus arteriosus in premature infants weighing between 500 and 1500 g, who are no more than 32 weeks gestational age when usual medical management (e.g., fluid restriction, diuretics, respiratory support, etc.

NIH genetic and rare disease info

• NIH info on Gorlin Chaudhry Moss syndrome

Gorlin Chaudhry Moss syndrome is a rare disease.

Gorlin Chaudhry Moss syndrome Resources
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