Prenatal diagnosis of SLC25A24 Fontaine progeroid syndrome: description of the fetal phenotype, genotype and detection of parental mosaicism.

Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101701004 Publication Model: Print Cited Medium: Internet ISSN: 2472-1727 (Electronic) NLM ISO Abbreviation: Birth Defects Res Subsets: MEDLINE

Original Publication: Hoboken, N.J. : John Wiley & Sons, Inc.

Mosaicism*/embryology ; Phenotype* ; Prenatal Diagnosis*/methods ; Progeria*/genetics; Adult ; Female ; Humans ; Male ; Pregnancy ; Antiporters ; Calcium-Binding Proteins ; Fetus ; Genotype ; Mitochondrial Proteins/genetics ; Mutation/genetics

Background: Fontaine progeroid syndrome (FPS, OMIM 612289) is a recently identified genetic disorder stemming from pathogenic variants in the SLC25A24 gene, encoding a mitochondrial carrier protein. It encompasses Gorlin-Chaudry-Moss syndrome and Fontaine-Farriaux syndrome, primarily manifesting as craniosynostosis with brachycephaly, distinctive dysmorphic facial features, hypertrichosis, severe prenatal and postnatal growth restriction, limb shortening, and early aging with characteristic skin changes, phalangeal anomalies, and genital malformations.
Cases: All known occurrences of FPS have been postnatally observed until now. Here, we present the first two prenatal cases identified during the second trimester of pregnancy. While affirming the presence of most postnatal abnormalities in prenatal cases, we note the absence of a progeroid appearance in young fetuses. Notably, our reports introduce new phenotypic features like encephalocele and nephromegaly, which were previously unseen postnatally. Moreover, paternal SLC25A24 mosaicism was detected in one case.
Conclusions: We present the initial two fetal instances of FPS, complemented by thorough phenotypic and genetic assessments. Our findings expand the phenotypical spectrum of FPS, unveiling new fetal phenotypic characteristics. Furthermore, one case underscores a potential novel inheritance pattern in this disorder. Lastly, our observations emphasize the efficacy of exome/genome sequencing in both prenatal and postmortem diagnosis of rare polymalformative syndromes with a normal karyotype and array-based comparative genomic hybridization (CGH).
(© 2024 The Author(s). Birth Defects Research published by Wiley Periodicals LLC.)

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Keywords: 2D/3D ultrasound; Fontaine progeroid syndrome; SLC25A24; craniofacial dysostosis; dysmorphic facial features; fetal growth restriction; fetus; mitochondrial disease; mosaicism

0 (Antiporters)
0 (Calcium-Binding Proteins)
0 (Mitochondrial Proteins)
0 (SLC25A24 protein, human)

Date Created: 20240709 Date Completed: 20240709 Latest Revision: 20240731

20240801

10.1002/bdr2.2380

38980211