Fontaine Progeroid Syndrome
Fontaine progeroid syndrome is a rare disease which is a genetic syndrome that is often diagnosed before birth.This syndrome is also known as Gorlin-Chaudhry-Moss syndrome, Craniofacial Dysostosis, Hypertrichosis, and Hypoplasia Of Labia Majora.
Fontaine progeroid syndrome is a multisystem connective tissue disorder characterized by poor growth, abnormal skeletal features, and distinctive craniofacial features with sagging, thin skin, and decreased subcutaneous fat suggesting an aged appearance that is most pronounced in infancy and improves with time.
Fontaine progeroid syndrome is a condition that affects many parts of the body. The signs and symptoms of this disorder are apparent from birth or infancy.
• One of the main symptoms of the syndrome is a severe growth retardation both before and after birth.
• Fontaine progeroid 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 Fontaine progeroid 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).
Fontaine Progeroid Syndrome (FPS) is an autosomal dominant condition caused by pathogenic variants in the SLC25A24 gene located on chromosome 1 and platelet disorder, familial, with associated myeloid malignancy.
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.
Risk Factor for future pregnancy –
SLC25A24 Fontaine progeroid syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Risk to future pregnancies is presumed to be low as the proband most likely has a de novo SLC25A24 pathogenic variant. However, given a recurrence risk (~1%) to sibs based on the theoretic possibility of parental germline mosaicism, prenatal and preimplantation genetic testing may be considered.
The diagnosis of SLC25A24 Fontaine progeroid syndrome is established in a proband with suggestive findings and a heterozygous pathogenic variant in SLC25A24 identified by molecular genetic testing.
Management, which is largely symptomatic, may be performed by specialists in multiple disciplines, including a craniofacial clinic (involving plastic surgery, neurosurgery, and otolaryngology), cardiology, pulmonology, gastroenterology, and clinical genetics. Some students may benefit from an individualized education plan through their school.
The life expectancy of many individuals with the condition is short, with many individuals not living past infancy or early childhood.
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