Clinical characteristics: SLC25A24 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. Characteristic radiographic features include turribrachycephaly with widely open anterior fontanelle, craniosynostosis, and anomalies of the terminal phalanges. Cardiovascular, genitourinary, ocular, and gastrointestinal abnormalities may also occur. To date, 13 individuals with a molecularly confirmed diagnosis of SLC25A24 Fontaine progeroid syndrome have been described.
Diagnosis/testing: 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: Treatment of manifestations: 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.
Surveillance: Routine evaluation to assess development of new manifestations and response to ongoing management.
Agents/circumstances to avoid: Contact sports and isometric exercise may need to be restricted if cranial anomalies and/or aortic dilatation are present.
Genetic counseling: 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.
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