Fontaine Progeroid Syndrome

Mendelian MONDO:0012853 Pathograph 7 Progeroid syndrome Mitochondrial disease Craniosynostosis syndrome

Fontaine progeroid syndrome is an ultra-rare autosomal dominant disorder usually caused by de novo heterozygous missense variants affecting codon 217 of SLC25A24. SLC25A24 encodes a mitochondrial inner-membrane ATP-Mg/Pi carrier. Disease-associated variants perturb mitochondrial carrier dynamics, ATP-linked mitochondrial respiration, mitochondrial morphology, and oxidative stress responses, producing prenatal and postnatal growth restriction, craniosynostosis or craniofacial dysostosis, progeroid skin and lipoatrophy, hypertrichosis, distal phalangeal anomalies, dental and ocular findings, and variable cardiovascular, genitourinary, gastrointestinal, and survival outcomes.

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1
Mappings
2
Definitions
1
Inheritance
4
Pathophys.
53
Phenotypes
7
Pathograph
1
Genes
2
Treatments
2
Subtypes
9
References
1
Deep Research
🔗

Mappings

MONDO
MONDO:0012853 Fontaine progeroid syndrome
skos:exactMatch Orphanet ORPHA:2963
Orphanet ORPHA:2963 lists MONDO:0012853 as an exact cross-reference for progeroid syndrome, Petty type, a historical Fontaine progeroid syndrome subtype.
📘

Definitions

2
Orphanet Petty type definition
A rare premature aging syndrome with prenatal and postnatal growth retardation, congenital progeroid craniofacial appearance, reduced subcutaneous fat, cutis laxa, and associated hair, nail, dental, distal phalanx, umbilical hernia, and ocular findings.
OTHER
Show evidence (2 references)
ORPHA:2963 SUPPORT Other
"Progeroid syndrome, Petty type is a rare premature aging syndrome characterized by pre-and postnatal growth retardation"
Orphanet defines the Petty type progeroid phenotype.
PMID:35679445 SUPPORT Human Clinical
"SLC25A24 Fontaine progeroid syndrome is a multisystem connective tissue disorder characterized by poor growth, abnormal skeletal features"
GeneReviews supports the multisystem connective-tissue disease definition.
Molecular diagnosis definition
The molecular diagnosis is established in a proband with suggestive findings and a heterozygous pathogenic SLC25A24 variant.
OTHER
Show evidence (1 reference)
PMID:35679445 SUPPORT Human Clinical
"established in a proband with suggestive findings and a heterozygous pathogenic variant in SLC25A24 identified by molecular genetic testing."
GeneReviews defines the molecular diagnostic criterion.
👪

Inheritance

1
Autosomal dominant, usually de novo HP:0000006
Fontaine progeroid syndrome is autosomal dominant and is typically caused by a de novo heterozygous SLC25A24 pathogenic variant; rare parental mosaicism can increase recurrence risk.
Autosomal dominant inheritance
Show evidence (3 references)
ORPHA:2963 SUPPORT Other
"Autosomal dominant"
Orphanet records autosomal dominant inheritance for the Petty type subtype.
PMID:35679445 SUPPORT Human Clinical
"SLC25A24 Fontaine progeroid syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant."
GeneReviews states the inheritance mode and typical de novo origin.
PMID:38980211 SUPPORT Human Clinical
"paternal SLC25A24 mosaicism was detected in one case."
Prenatal case evidence supports parental mosaicism as a recurrence-risk mechanism.
◆

Subtypes

2
Progeroid syndrome, Petty type
Historical clinical subtype also called Petty syndrome or Petty-Laxova-Wiedemann syndrome. Orphanet maps this subtype exactly to the MONDO Fontaine progeroid syndrome term and records autosomal dominant inheritance and SLC25A24 involvement.
Show evidence (2 references)
ORPHA:2963 SUPPORT Other
"Petty-Laxova-Wiedemann syndrome"
Orphanet lists Petty-Laxova-Wiedemann syndrome as a synonym for this subtype.
ORPHA:2963 SUPPORT Other
"Autosomal dominant"
Orphanet records autosomal dominant inheritance for the Petty type subtype.
Gorlin-Chaudhry-Moss syndrome
Historical clinical subtype characterized by craniofacial dysostosis, facial dysmorphism, conductive hearing loss, generalized hypertrichosis, and extremity, ocular, and dental anomalies. Molecular literature supports integration with Fontaine progeroid syndrome through de novo SLC25A24 variants.
Show evidence (2 references)
ORPHA:2095 SUPPORT Other
"Gorlin-Chaudhry-Moss (GCM) syndrome is a multiple congenital anomaly syndrome characterized by craniofacial dysostosis"
Orphanet defines the historical GCM subtype.
PMID:31775791 SUPPORT Human Clinical
"it has been proposed recently that they be integrated into a single disorder under the name of Fontaine progeroid syndrome (FPS)."
This case report summarizes the molecular reclassification of GCMS and FFS as Fontaine progeroid syndrome.
⚙

Pathophysiology

4
SLC25A24 codon 217 carrier dysfunction
Heterozygous de novo missense variants at Arg217 alter the SLC25A24 mitochondrial ATP-Mg/phosphate carrier and disrupt its transport dynamics.
SLC25A24 link
mitochondrial transport link ⚠ ABNORMAL ATP metabolic process link ⚠ ABNORMAL
mitochondrial inner membrane link
Downstream
Abnormal mitochondrial energy metabolism Defective ATP-Mg/phosphate carrier dynamics disrupt mitochondrial ATP-linked respiration and membrane physiology.
Show evidence (3 references)
PMID:29100093 SUPPORT Human Clinical
"SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/Pi carrier."
The discovery paper identifies the affected protein as a mitochondrial inner-membrane carrier.
PMID:29100094 SUPPORT Human Clinical
"SLC25A24 allows an electro-neutral and reversible exchange of ATP-Mg and phosphate between the cytosol and mitochondria"
This supports the normal carrier function disrupted by disease variants.
PMID:29100094 SUPPORT Computational
"p.Arg217Cys and p.Arg217His narrow the substrate cavity of the protein and disrupt transporter dynamics."
Molecular-dynamics modeling supports altered carrier dynamics at the recurrent variant site.
Abnormal mitochondrial energy metabolism
Patient-derived fibroblasts and cells expressing SLC25A24 Arg217 variants show abnormal mitochondrial morphology, reduced ATP-linked oxygen consumption, lower mitochondrial matrix ATP, and membrane-potential hyperpolarization.
fibroblast link
oxidative phosphorylation link ↓ DECREASED proton motive force-driven mitochondrial ATP synthesis link ↓ DECREASED mitochondrion organization link ⚠ ABNORMAL
mitochondrion link
Downstream
Oxidative stress-sensitive mitochondrial swelling Bioenergetic membrane defects make patient cells sensitive to oxidative-stress-induced mitochondrial swelling.
Skeletal and connective tissue developmental abnormalities Mitochondrial carrier dysfunction is linked experimentally to skeletal and connective-tissue development.
Show evidence (3 references)
PMID:29100094 SUPPORT In Vitro
"showed altered mitochondrial morphology, a decreased proliferation rate, increased mitochondrial membrane potential, and decreased ATP-linked mitochondrial oxygen consumption."
Patient fibroblast and expression-system data support abnormal mitochondrial bioenergetics.
PMID:29100093 SUPPORT In Vitro
"ATP content in the mitochondrial matrix was lower than that in control cells."
Patient fibroblast data support reduced mitochondrial matrix ATP.
PMID:41271664 SUPPORT Human Clinical
"decreased activity of mitochondrial respiratory chain enzyme activity."
Clinical case evidence supports overt mitochondrial respiratory-chain involvement in at least one patient.
Oxidative stress-sensitive mitochondrial swelling
SLC25A24-mutant cells develop mitochondrial swelling, especially after hydrogen peroxide exposure, indicating abnormal response to oxidative stress.
fibroblast link
response to oxidative stress link ⚠ ABNORMAL mitochondrion organization link ⚠ ABNORMAL
Downstream
Skeletal and connective tissue developmental abnormalities Oxidative-stress-sensitive mitochondrial dysfunction is part of the mechanism linked to skeletal and connective-tissue manifestations.
Show evidence (2 references)
PMID:29100093 SUPPORT In Vitro
"the probands' cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H2O2)."
Patient fibroblast experiments directly support oxidative-stress-sensitive mitochondrial swelling.
PMID:29100093 SUPPORT In Vitro
"mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations."
The authors interpret the cell findings as mutation-driven oxidative-stress sensitivity.
Skeletal and connective tissue developmental abnormalities
The mitochondrial ATP-Mg/Pi carrier defect is linked to skeletal and connective-tissue development, matching the craniosynostosis, bone dysplasia, progeroid skin, lipoatrophy, and distal phalangeal phenotype.
skeletal system development link ⚠ ABNORMAL connective tissue development link ⚠ ABNORMAL
Show evidence (2 references)
PMID:29100093 SUPPORT In Vitro
"link mitochondrial ATP-Mg/Pi transport to the development of skeletal and connective tissue."
The discovery study links the mitochondrial carrier defect to skeletal and connective-tissue development.
PMID:29100094 SUPPORT Human Clinical
"early aging, especially evident in congenitally decreased subcutaneous fat tissue and sparse hair, bone dysplasia of the skull and fingers"
Human clinical features support skeletal and connective-tissue involvement.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Fontaine Progeroid Syndrome Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

53
Cardiovascular 1
Patent ductus arteriosus FREQUENT Patent ductus arteriosus (HP:0001643)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0001643 | Patent ductus arteriosus | Frequent (79-30%)"
Orphanet provides the GCM phenotype association and frequency band.
Ear 1
Conductive hearing impairment VERY_FREQUENT Conductive hearing impairment (HP:0000405)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000405 | Conductive hearing impairment | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Eye 4
Hypertelorism VERY_FREQUENT Hypertelorism (HP:0000316)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000316 | Hypertelorism | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Strabismus VERY_FREQUENT Strabismus (HP:0000486)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000486 | Strabismus | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Nystagmus VERY_FREQUENT Nystagmus (HP:0000639)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000639 | Nystagmus | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Sclerocornea FREQUENT Sclerocornea (HP:0000647)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000647 | Sclerocornea | Frequent (79-30%)"
Orphanet provides the GCM phenotype association and frequency band.
Head and Neck 6
Brachycephaly VERY_FREQUENT Brachycephaly (HP:0000248)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000248 | Brachycephaly | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Coronal craniosynostosis VERY_FREQUENT Coronal craniosynostosis (HP:0004440)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0004440 | Coronal craniosynostosis | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Epicanthus VERY_FREQUENT Epicanthus (HP:0000286)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000286 | Epicanthus | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Tooth agenesis VERY_FREQUENT Tooth agenesis (HP:0009804)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0009804 | Tooth agenesis | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Abnormality of the dentition VERY_FREQUENT Abnormality of the dentition (HP:0000164)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000164 | Abnormality of the dentition | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Oligodontia VERY_FREQUENT Oligodontia (HP:0000677)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000677 | Oligodontia | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Integument 6
Cutis laxa VERY_FREQUENT Cutis laxa (HP:0000973)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000973 | Cutis laxa | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Redundant skin VERY_FREQUENT Redundant skin (HP:0001582)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0001582 | Redundant skin | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Prematurely aged appearance VERY_FREQUENT Prematurely aged appearance (HP:0007495)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0007495 | Prematurely aged appearance | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Shagreen patch VERY_FREQUENT Shagreen patch (HP:0009721)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0009721 | Shagreen patch | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Abnormality of the nail VERY_FREQUENT Abnormal nail morphology (HP:0001597)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0001597 | Abnormality of the nail | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Sparse hair VERY_FREQUENT Sparse hair (HP:0008070)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0008070 | Sparse hair | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Nervous System 1
Mild intellectual disability OCCASIONAL Mild intellectual disability (HP:0001256)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0001256 | Intellectual disability, mild | Occasional (29-5%)"
Orphanet provides the GCM phenotype association and frequency band.
Growth 3
Intrauterine growth retardation VERY_FREQUENT Intrauterine growth retardation (HP:0001511)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0001511 | Intrauterine growth retardation | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Failure to thrive VERY_FREQUENT Failure to thrive (HP:0001508)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0001508 | Failure to thrive | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Short stature VERY_FREQUENT Short stature (HP:0004322)
Show evidence (2 references)
ORPHA:2963 SUPPORT Other
"HP:0004322 | Short stature | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
ORPHA:2095 SUPPORT Other
"HP:0004322 | Short stature | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Other 31
Wide anterior fontanel VERY_FREQUENT Wide anterior fontanel (HP:0000260)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000260 | Wide anterior fontanel | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Broad forehead VERY_FREQUENT Broad forehead (HP:0000337)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000337 | Broad forehead | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Mandibular prognathia VERY_FREQUENT Mandibular prognathia (HP:0000303)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000303 | Mandibular prognathia | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Posteriorly rotated ears VERY_FREQUENT Posteriorly rotated ears (HP:0000358)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000358 | Posteriorly rotated ears | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Low anterior hairline VERY_FREQUENT Low anterior hairline (HP:0000294)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000294 | Low anterior hairline | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Congenital craniofacial dysostosis VERY_FREQUENT Congenital craniofacial dysostosis (HP:0008497)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0008497 | Congenital craniofacial dysostosis | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Hypoplasia of the maxilla FREQUENT Hypoplasia of the maxilla (HP:0000327)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000327 | Hypoplasia of the maxilla | Frequent (79-30%)"
Orphanet provides the GCM phenotype association and frequency band.
Abnormal skull morphology FREQUENT Abnormal skull morphology (HP:0000929)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000929 | Abnormal skull morphology | Frequent (79-30%)"
Orphanet provides the GCM phenotype association and frequency band.
Aplasia or hypoplasia of the nasal bone FREQUENT Aplasia/Hypoplasia of the nasal bone (HP:0010940)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0010940 | Aplasia/Hypoplasia of the nasal bone | Frequent (79-30%)"
Orphanet provides the GCM phenotype association and frequency band.
Reduced subcutaneous adipose tissue VERY_FREQUENT Reduced subcutaneous adipose tissue (HP:0003758)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0003758 | Reduced subcutaneous adipose tissue | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Lipoatrophy VERY_FREQUENT Lipoatrophy (HP:0100578)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0100578 | Lipoatrophy | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Generalized hirsutism VERY_FREQUENT Generalized hirsutism (HP:0002230)
Show evidence (2 references)
ORPHA:2963 SUPPORT Other
"HP:0002230 | Generalized hirsutism | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
ORPHA:2095 SUPPORT Other
"HP:0002230 | Generalized hirsutism | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Abnormality of the hair VERY_FREQUENT Abnormal hair morphology (HP:0001595)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0001595 | Abnormality of the hair | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Brittle hair VERY_FREQUENT Brittle hair (HP:0002299)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0002299 | Brittle hair | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Thick eyebrow VERY_FREQUENT Thick eyebrow (HP:0000574)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000574 | Thick eyebrow | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Long eyelashes in irregular rows VERY_FREQUENT Long eyelashes in irregular rows (HP:0007740)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0007740 | Long eyelashes in irregular rows | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Coarse hair VERY_FREQUENT Coarse hair (HP:0002208)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0002208 | Coarse hair | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Abnormality of the eye VERY_FREQUENT Abnormality of the eye (HP:0000478)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000478 | Abnormality of the eye | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Abnormal eyelid morphology VERY_FREQUENT Abnormal eyelid morphology (HP:0000492)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000492 | Abnormal eyelid morphology | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Abnormality of vision VERY_FREQUENT Abnormality of vision (HP:0000504)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000504 | Abnormality of vision | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Astigmatism FREQUENT Astigmatism (HP:0000483)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000483 | Astigmatism | Frequent (79-30%)"
Orphanet provides the GCM phenotype association and frequency band.
Upper eyelid coloboma OCCASIONAL Upper eyelid coloboma (HP:0000636)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0000636 | Upper eyelid coloboma | Occasional (29-5%)"
Orphanet provides the GCM phenotype association and frequency band.
Short distal phalanx of finger VERY_FREQUENT Short distal phalanx of finger (HP:0009882)
Show evidence (2 references)
ORPHA:2963 SUPPORT Other
"HP:0009882 | Short distal phalanx of finger | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
ORPHA:2095 SUPPORT Other
"HP:0009882 | Short distal phalanx of finger | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Decreased skull ossification VERY_FREQUENT Decreased skull ossification (HP:0004331)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0004331 | Decreased skull ossification | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Abnormal foot morphology VERY_FREQUENT Abnormal foot morphology (HP:0001760)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0001760 | Abnormal foot morphology | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Abnormal metacarpal morphology VERY_FREQUENT Abnormal metacarpal morphology (HP:0005916)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0005916 | Abnormal metacarpal morphology | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
Abnormal dermatoglyphics VERY_FREQUENT Abnormal dermatoglyphics (HP:0007477)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0007477 | Abnormal dermatoglyphics | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Umbilical hernia in Petty type VERY_FREQUENT Umbilical hernia (HP:0001537)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0001537 | Umbilical hernia | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Umbilical hernia in GCM type FREQUENT Umbilical hernia (HP:0001537)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0001537 | Umbilical hernia | Frequent (79-30%)"
Orphanet provides the GCM phenotype association and frequency band.
Everted lower lip vermilion VERY_FREQUENT Everted lower lip vermilion (HP:0000232)
Show evidence (1 reference)
ORPHA:2963 SUPPORT Other
"HP:0000232 | Everted lower lip vermilion | Very frequent (99-80%)"
Orphanet provides the Petty type phenotype association and frequency band.
Underdeveloped supraorbital ridges VERY_FREQUENT Underdeveloped supraorbital ridges (HP:0009891)
Show evidence (1 reference)
ORPHA:2095 SUPPORT Other
"HP:0009891 | Underdeveloped supraorbital ridges | Very frequent (99-80%)"
Orphanet provides the GCM phenotype association and frequency band.
🧬

Genetic Associations

1
SLC25A24 (Heterozygous pathogenic missense variants, usually de novo)
Show evidence (4 references)
ORPHA:2963 SUPPORT Other
"SLC25A24 | solute carrier family 25 member 24 | hgnc:20662 | Disease-causing germline mutation(s) in"
Orphanet identifies SLC25A24 as the disease-causing gene.
PMID:29100093 SUPPORT Human Clinical
"we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls"
Human discovery series identifies recurrent de novo SLC25A24 variants.
PMID:29100094 SUPPORT Human Clinical
"all carried the de novo missense variant c.649C>T (p.Arg217Cys) or c.650G>A (p.Arg217His) in SLC25A24"
Independent case series identifies the same de novo codon 217 variants.
+ 1 more reference
💊

Treatments

2
Multidisciplinary symptomatic management
Action: supportive care MAXO:0000950
Management is largely symptomatic and coordinated across craniofacial, cardiology, pulmonology, gastroenterology, otolaryngology, genetics, and developmental supports according to the manifestations present.
Target Phenotypes: Craniosynostosis ↗ Patent ductus arteriosus ↗
Show evidence (1 reference)
PMID:35679445 SUPPORT Human Clinical
"Management, which is largely symptomatic, may be performed by specialists in multiple disciplines"
GeneReviews supports symptomatic multidisciplinary care.
Routine clinical surveillance
Action: clinical assessment MAXO:0000487
Ongoing surveillance assesses emerging manifestations and treatment response, including development, cranial, cardiovascular, pulmonary, gastrointestinal, and other system-specific complications.
Show evidence (1 reference)
PMID:35679445 SUPPORT Human Clinical
"Routine evaluation to assess development of new manifestations and response to ongoing management."
GeneReviews supports surveillance through routine clinical assessment.
{ }

Source YAML

click to show 
name: Fontaine Progeroid Syndrome
creation_date: "2026-05-07T05:07:00Z"
updated_date: "2026-05-07T05:07:00Z"
category: Mendelian
parents:
- Progeroid syndrome
- Mitochondrial disease
- Craniosynostosis syndrome
synonyms:
- SLC25A24 Fontaine progeroid syndrome
- FPS
- Fontaine syndrome
- Gorlin-Chaudhry-Moss syndrome
- GCM syndrome
- Progeroid syndrome, Petty type
- Petty-Laxova-Wiedemann syndrome
description: >-
  Fontaine progeroid syndrome is an ultra-rare autosomal dominant disorder
  usually caused by de novo heterozygous missense variants affecting codon 217
  of SLC25A24. SLC25A24 encodes a mitochondrial inner-membrane ATP-Mg/Pi
  carrier. Disease-associated variants perturb mitochondrial carrier dynamics,
  ATP-linked mitochondrial respiration, mitochondrial morphology, and oxidative
  stress responses, producing prenatal and postnatal growth restriction,
  craniosynostosis or craniofacial dysostosis, progeroid skin and lipoatrophy,
  hypertrichosis, distal phalangeal anomalies, dental and ocular findings, and
  variable cardiovascular, genitourinary, gastrointestinal, and survival
  outcomes.
disease_term:
  preferred_term: Fontaine progeroid syndrome
  term:
    id: MONDO:0012853
    label: Fontaine progeroid syndrome
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0012853
      label: Fontaine progeroid syndrome
    mapping_predicate: skos:exactMatch
    mapping_source: Orphanet ORPHA:2963
    mapping_justification: >-
      Orphanet ORPHA:2963 lists MONDO:0012853 as an exact cross-reference for
      progeroid syndrome, Petty type, a historical Fontaine progeroid syndrome
      subtype.
external_assertions:
- name: Orphanet Fontaine progeroid syndrome disease record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:697101
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=697101
  description: >-
    Orphanet's ORPHA:697101 record defines Fontaine progeroid syndrome as a
    disease-level record and links it exactly to OMIM:612289.
  evidence:
  - reference: ORPHA:697101
    reference_title: "Fontaine progeroid syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "OMIM:612289 | Exact"
    explanation: Orphanet maps the disease-level Fontaine progeroid syndrome record to OMIM:612289.
- name: Orphanet Petty type subtype record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:2963
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2963
  description: >-
    Orphanet's ORPHA:2963 structured subtype record provides the Petty type
    definition, autosomal dominant inheritance, SLC25A24 gene association,
    epidemiology, MONDO mapping, and HPO phenotype rows used in this entry.
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "MONDO:0012853 | Exact"
    explanation: Orphanet maps ORPHA:2963 exactly to the MONDO term used by this entry.
- name: Orphanet Gorlin-Chaudhry-Moss subtype record
  source: Orphanet
  assertion_type: structured_disease_record
  external_id: ORPHA:2095
  url: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2095
  description: >-
    Orphanet's ORPHA:2095 structured subtype record provides historical
    Gorlin-Chaudhry-Moss syndrome synonyms, definition, SLC25A24 gene
    association, epidemiology, and HPO phenotype rows used in this entry.
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SLC25A24 | solute carrier family 25 member 24 | hgnc:20662 | Disease-causing germline mutation(s) in"
    explanation: Orphanet identifies SLC25A24 as the disease-causing gene for the historical GCM subtype.
definitions:
- name: Orphanet Petty type definition
  definition_type: OTHER
  description: >-
    A rare premature aging syndrome with prenatal and postnatal growth
    retardation, congenital progeroid craniofacial appearance, reduced
    subcutaneous fat, cutis laxa, and associated hair, nail, dental, distal
    phalanx, umbilical hernia, and ocular findings.
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Progeroid syndrome, Petty type is a rare premature aging syndrome characterized by pre-and postnatal growth retardation"
    explanation: Orphanet defines the Petty type progeroid phenotype.
  - reference: PMID:35679445
    reference_title: SLC25A24 Fontaine Progeroid Syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "SLC25A24 Fontaine progeroid syndrome is a multisystem connective tissue disorder characterized by poor growth, abnormal skeletal features"
    explanation: GeneReviews supports the multisystem connective-tissue disease definition.
- name: Molecular diagnosis definition
  definition_type: OTHER
  description: >-
    The molecular diagnosis is established in a proband with suggestive
    findings and a heterozygous pathogenic SLC25A24 variant.
  evidence:
  - reference: PMID:35679445
    reference_title: SLC25A24 Fontaine Progeroid Syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "established in a proband with suggestive findings and a heterozygous pathogenic variant in SLC25A24 identified by molecular genetic testing."
    explanation: GeneReviews defines the molecular diagnostic criterion.
references:
- reference: ORPHA:2963
  title: Progeroid syndrome, Petty type
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      Orphanet maps the Petty type subtype exactly to MONDO:0012853 and
      provides autosomal dominant inheritance, SLC25A24, epidemiology, and HPO
      phenotype rows.
    supporting_text: "MONDO:0012853 | Exact"
- reference: ORPHA:2095
  title: Gorlin-Chaudhry-Moss syndrome
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      Orphanet records the historical Gorlin-Chaudhry-Moss subtype with
      SLC25A24 and structured HPO phenotype rows.
    supporting_text: "SLC25A24 | solute carrier family 25 member 24 | hgnc:20662 | Disease-causing germline mutation(s) in"
- reference: ORPHA:697101
  title: Fontaine progeroid syndrome
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      Orphanet records Fontaine progeroid syndrome as a disease-level record
      with an exact OMIM mapping.
    supporting_text: "OMIM:612289 | Exact"
- reference: PMID:35679445
  title: SLC25A24 Fontaine Progeroid Syndrome.
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      GeneReviews summarizes Fontaine progeroid syndrome clinical features,
      molecular diagnosis, management, surveillance, and autosomal dominant
      mostly de novo inheritance.
    supporting_text: "SLC25A24 Fontaine progeroid syndrome is a multisystem connective tissue disorder"
- reference: PMID:29100093
  title: "De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction."
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      A GCMS cohort identified recurrent de novo SLC25A24 variants and showed
      mitochondrial swelling, low matrix ATP, oxidative-stress sensitivity, and
      gain of pathological function.
    supporting_text: "These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations."
- reference: PMID:29100094
  title: "De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise."
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      A second discovery series named Fontaine syndrome and linked codon 217
      SLC25A24 variants to impaired ATP-Mg/phosphate transport dynamics and
      abnormal mitochondrial energy metabolism.
    supporting_text: "Our findings identify SLC25A24 mutations affecting codon 217 as the underlying genetic cause of human progeroid Fontaine syndrome."
- reference: PMID:31775791
  title: "A 9-year-old Korean girl with Fontaine progeroid syndrome: a case report with further phenotypical delineation and description of clinical course during long-term follow-up."
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      Long-term case follow-up supports integrating GCMS and FFS under
      Fontaine progeroid syndrome and documents typical clinical features with
      a de novo SLC25A24 variant.
    supporting_text: "it has been proposed recently that they be integrated into a single disorder under the name of Fontaine progeroid syndrome (FPS)."
- reference: PMID:38980211
  title: "Prenatal diagnosis of SLC25A24 Fontaine progeroid syndrome: description of the fetal phenotype, genotype and detection of parental mosaicism."
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      Prenatal cases support the fetal phenotype, exome/genome diagnostic
      utility, and possible parental mosaicism in recurrence risk.
    supporting_text: "paternal SLC25A24 mosaicism was detected in one case."
- reference: PMID:41271664
  title: Fontaine progeroid syndrome with neonatal mitochondrial disease.
  found_in:
  - Fontaine_Progeroid_Syndrome-deep-research-fallback.md
  findings:
  - statement: >-
      A neonatal case directly diagnosed mitochondrial disease in Fontaine
      progeroid syndrome with decreased respiratory chain enzyme activity.
    supporting_text: "decreased activity of mitochondrial respiratory chain enzyme activity."
has_subtypes:
- name: Petty type
  display_name: Progeroid syndrome, Petty type
  classification: historical_clinical_name
  description: >-
    Historical clinical subtype also called Petty syndrome or
    Petty-Laxova-Wiedemann syndrome. Orphanet maps this subtype exactly to the
    MONDO Fontaine progeroid syndrome term and records autosomal dominant
    inheritance and SLC25A24 involvement.
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Petty-Laxova-Wiedemann syndrome"
    explanation: Orphanet lists Petty-Laxova-Wiedemann syndrome as a synonym for this subtype.
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal dominant"
    explanation: Orphanet records autosomal dominant inheritance for the Petty type subtype.
- name: GCM type
  display_name: Gorlin-Chaudhry-Moss syndrome
  classification: historical_clinical_name
  description: >-
    Historical clinical subtype characterized by craniofacial dysostosis,
    facial dysmorphism, conductive hearing loss, generalized hypertrichosis,
    and extremity, ocular, and dental anomalies. Molecular literature supports
    integration with Fontaine progeroid syndrome through de novo SLC25A24
    variants.
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Gorlin-Chaudhry-Moss (GCM) syndrome is a multiple congenital anomaly syndrome characterized by craniofacial dysostosis"
    explanation: Orphanet defines the historical GCM subtype.
  - reference: PMID:31775791
    reference_title: "A 9-year-old Korean girl with Fontaine progeroid syndrome: a case report with further phenotypical delineation and description of clinical course during long-term follow-up."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "it has been proposed recently that they be integrated into a single disorder under the name of Fontaine progeroid syndrome (FPS)."
    explanation: This case report summarizes the molecular reclassification of GCMS and FFS as Fontaine progeroid syndrome.
prevalence:
- population: Worldwide
  subtype: Petty type
  percentage: <1 per 1,000,000
  notes: Orphanet records worldwide point prevalence below one per million for the Petty type subtype.
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "<1 / 1 000 000 | Worldwide | Point prevalence | PMID:2309786"
    explanation: Orphanet provides the point-prevalence category for this subtype.
- population: Worldwide
  subtype: GCM type
  percentage: <1 per 1,000,000
  notes: Orphanet records worldwide point prevalence below one per million for the GCM subtype.
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "<1 / 1 000 000 | Worldwide | Point prevalence | ORPHANET"
    explanation: Orphanet provides the point-prevalence category for this subtype.
progression:
- phase: Prenatal and neonatal onset
  age_range: Prenatal to neonatal
  notes: >-
    Growth restriction and malformations can be recognized prenatally or at
    birth. The progeroid skin appearance may be most pronounced in infancy and
    can improve with time in survivors.
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Neonatal"
    explanation: Orphanet records neonatal onset for Petty type.
  - reference: PMID:38980211
    reference_title: "Prenatal diagnosis of SLC25A24 Fontaine progeroid syndrome: description of the fetal phenotype, genotype and detection of parental mosaicism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the first two prenatal cases identified during the second trimester of pregnancy."
    explanation: The prenatal series supports fetal recognition of the syndrome.
  - reference: PMID:35679445
    reference_title: SLC25A24 Fontaine Progeroid Syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "an aged appearance that is most pronounced in infancy and improves with time."
    explanation: GeneReviews supports evolution of the progeroid appearance over time.
- phase: Variable survival
  age_range: Infancy to adolescence
  notes: >-
    Reported survival is variable, with early lethality in some patients and
    longer-term childhood or adolescent survival in others.
  evidence:
  - reference: PMID:36093452
    reference_title: Fontaine progeroid syndrome-A case report.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Eleven cases have been described in the literature, with early lethality in some."
    explanation: Case-report summary supports early lethality in a subset.
  - reference: PMID:31775791
    reference_title: "A 9-year-old Korean girl with Fontaine progeroid syndrome: a case report with further phenotypical delineation and description of clinical course during long-term follow-up."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "including growth and developmental achievements."
    explanation: Long-term follow-up supports childhood survival and developmental tracking.
inheritance:
- name: Autosomal dominant, usually de novo
  description: >-
    Fontaine progeroid syndrome is autosomal dominant and is typically caused
    by a de novo heterozygous SLC25A24 pathogenic variant; rare parental
    mosaicism can increase recurrence risk.
  inheritance_term:
    preferred_term: Autosomal dominant inheritance
    term:
      id: HP:0000006
      label: Autosomal dominant inheritance
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Autosomal dominant"
    explanation: Orphanet records autosomal dominant inheritance for the Petty type subtype.
  - reference: PMID:35679445
    reference_title: SLC25A24 Fontaine Progeroid Syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "SLC25A24 Fontaine progeroid syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant."
    explanation: GeneReviews states the inheritance mode and typical de novo origin.
  - reference: PMID:38980211
    reference_title: "Prenatal diagnosis of SLC25A24 Fontaine progeroid syndrome: description of the fetal phenotype, genotype and detection of parental mosaicism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "paternal SLC25A24 mosaicism was detected in one case."
    explanation: Prenatal case evidence supports parental mosaicism as a recurrence-risk mechanism.
genetic:
- name: SLC25A24
  association: Heterozygous pathogenic missense variants, usually de novo
  relationship_type: CAUSATIVE
  variant_origin: DE_NOVO
  presence: Positive
  gene_term:
    preferred_term: SLC25A24
    term:
      id: hgnc:20662
      label: SLC25A24
  notes: >-
    Recurrent pathogenic variants affect Arg217 in the mitochondrial carrier
    protein; functional evidence supports gain of pathological function rather
    than simple haploinsufficiency.
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SLC25A24 | solute carrier family 25 member 24 | hgnc:20662 | Disease-causing germline mutation(s) in"
    explanation: Orphanet identifies SLC25A24 as the disease-causing gene.
  - reference: PMID:29100093
    reference_title: "De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls"
    explanation: Human discovery series identifies recurrent de novo SLC25A24 variants.
  - reference: PMID:29100094
    reference_title: "De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "all carried the de novo missense variant c.649C>T (p.Arg217Cys) or c.650G>A (p.Arg217His) in SLC25A24"
    explanation: Independent case series identifies the same de novo codon 217 variants.
  - reference: CGGV:assertion_e194527a-5bb7-44ca-af69-f919f365a434-2025-09-18T040000.000Z
    reference_title: "SLC25A24 / Fontaine progeroid syndrome (Definitive)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "SLC25A24 | HGNC:20662 | Fontaine progeroid syndrome | MONDO:0012853 | AD | Definitive"
    explanation: ClinGen classifies the SLC25A24-Fontaine progeroid syndrome gene-disease relationship as definitive with autosomal dominant inheritance.
pathophysiology:
- name: SLC25A24 codon 217 carrier dysfunction
  description: >-
    Heterozygous de novo missense variants at Arg217 alter the SLC25A24
    mitochondrial ATP-Mg/phosphate carrier and disrupt its transport dynamics.
  genes:
  - preferred_term: SLC25A24
    term:
      id: hgnc:20662
      label: SLC25A24
  cellular_components:
  - preferred_term: mitochondrial inner membrane
    term:
      id: GO:0005743
      label: mitochondrial inner membrane
  biological_processes:
  - preferred_term: mitochondrial transport
    modifier: ABNORMAL
    term:
      id: GO:0006839
      label: mitochondrial transport
  - preferred_term: ATP metabolic process
    modifier: ABNORMAL
    term:
      id: GO:0046034
      label: ATP metabolic process
  evidence:
  - reference: PMID:29100093
    reference_title: "De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/Pi carrier."
    explanation: The discovery paper identifies the affected protein as a mitochondrial inner-membrane carrier.
  - reference: PMID:29100094
    reference_title: "De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "SLC25A24 allows an electro-neutral and reversible exchange of ATP-Mg and phosphate between the cytosol and mitochondria"
    explanation: This supports the normal carrier function disrupted by disease variants.
  - reference: PMID:29100094
    reference_title: "De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise."
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "p.Arg217Cys and p.Arg217His narrow the substrate cavity of the protein and disrupt transporter dynamics."
    explanation: Molecular-dynamics modeling supports altered carrier dynamics at the recurrent variant site.
  downstream:
  - target: Abnormal mitochondrial energy metabolism
    causal_link_type: DIRECT
    description: Defective ATP-Mg/phosphate carrier dynamics disrupt mitochondrial ATP-linked respiration and membrane physiology.
- name: Abnormal mitochondrial energy metabolism
  description: >-
    Patient-derived fibroblasts and cells expressing SLC25A24 Arg217 variants
    show abnormal mitochondrial morphology, reduced ATP-linked oxygen
    consumption, lower mitochondrial matrix ATP, and membrane-potential
    hyperpolarization.
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  cellular_components:
  - preferred_term: mitochondrion
    term:
      id: GO:0005739
      label: mitochondrion
  biological_processes:
  - preferred_term: oxidative phosphorylation
    modifier: DECREASED
    term:
      id: GO:0006119
      label: oxidative phosphorylation
  - preferred_term: proton motive force-driven mitochondrial ATP synthesis
    modifier: DECREASED
    term:
      id: GO:0042776
      label: proton motive force-driven mitochondrial ATP synthesis
  - preferred_term: mitochondrion organization
    modifier: ABNORMAL
    term:
      id: GO:0007005
      label: mitochondrion organization
  evidence:
  - reference: PMID:29100094
    reference_title: "De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "showed altered mitochondrial morphology, a decreased proliferation rate, increased mitochondrial membrane potential, and decreased ATP-linked mitochondrial oxygen consumption."
    explanation: Patient fibroblast and expression-system data support abnormal mitochondrial bioenergetics.
  - reference: PMID:29100093
    reference_title: "De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "ATP content in the mitochondrial matrix was lower than that in control cells."
    explanation: Patient fibroblast data support reduced mitochondrial matrix ATP.
  - reference: PMID:41271664
    reference_title: Fontaine progeroid syndrome with neonatal mitochondrial disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "decreased activity of mitochondrial respiratory chain enzyme activity."
    explanation: Clinical case evidence supports overt mitochondrial respiratory-chain involvement in at least one patient.
  downstream:
  - target: Oxidative stress-sensitive mitochondrial swelling
    causal_link_type: DIRECT
    description: Bioenergetic membrane defects make patient cells sensitive to oxidative-stress-induced mitochondrial swelling.
  - target: Skeletal and connective tissue developmental abnormalities
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Mitochondrial carrier dysfunction is linked experimentally to skeletal and connective-tissue development.
- name: Oxidative stress-sensitive mitochondrial swelling
  description: >-
    SLC25A24-mutant cells develop mitochondrial swelling, especially after
    hydrogen peroxide exposure, indicating abnormal response to oxidative
    stress.
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: response to oxidative stress
    modifier: ABNORMAL
    term:
      id: GO:0006979
      label: response to oxidative stress
  - preferred_term: mitochondrion organization
    modifier: ABNORMAL
    term:
      id: GO:0007005
      label: mitochondrion organization
  evidence:
  - reference: PMID:29100093
    reference_title: "De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "the probands' cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H2O2)."
    explanation: Patient fibroblast experiments directly support oxidative-stress-sensitive mitochondrial swelling.
  - reference: PMID:29100093
    reference_title: "De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations."
    explanation: The authors interpret the cell findings as mutation-driven oxidative-stress sensitivity.
  downstream:
  - target: Skeletal and connective tissue developmental abnormalities
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Oxidative-stress-sensitive mitochondrial dysfunction is part of the mechanism linked to skeletal and connective-tissue manifestations.
- name: Skeletal and connective tissue developmental abnormalities
  description: >-
    The mitochondrial ATP-Mg/Pi carrier defect is linked to skeletal and
    connective-tissue development, matching the craniosynostosis, bone
    dysplasia, progeroid skin, lipoatrophy, and distal phalangeal phenotype.
  biological_processes:
  - preferred_term: skeletal system development
    modifier: ABNORMAL
    term:
      id: GO:0001501
      label: skeletal system development
  - preferred_term: connective tissue development
    modifier: ABNORMAL
    term:
      id: GO:0061448
      label: connective tissue development
  evidence:
  - reference: PMID:29100093
    reference_title: "De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "link mitochondrial ATP-Mg/Pi transport to the development of skeletal and connective tissue."
    explanation: The discovery study links the mitochondrial carrier defect to skeletal and connective-tissue development.
  - reference: PMID:29100094
    reference_title: "De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "early aging, especially evident in congenitally decreased subcutaneous fat tissue and sparse hair, bone dysplasia of the skull and fingers"
    explanation: Human clinical features support skeletal and connective-tissue involvement.
phenotypes:
- category: Growth
  name: Intrauterine growth retardation
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Intrauterine growth retardation
    term:
      id: HP:0001511
      label: Intrauterine growth retardation
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001511 | Intrauterine growth retardation | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Growth
  name: Failure to thrive
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Failure to thrive
    term:
      id: HP:0001508
      label: Failure to thrive
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001508 | Failure to thrive | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Growth
  name: Short stature
  frequency: VERY_FREQUENT
  subtypes:
  - Petty type
  - GCM type
  phenotype_term:
    preferred_term: Short stature
    term:
      id: HP:0004322
      label: Short stature
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0004322 | Short stature | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0004322 | Short stature | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Craniofacial
  name: Wide anterior fontanel
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Wide anterior fontanel
    term:
      id: HP:0000260
      label: Wide anterior fontanel
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000260 | Wide anterior fontanel | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Craniofacial
  name: Broad forehead
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Broad forehead
    term:
      id: HP:0000337
      label: Broad forehead
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000337 | Broad forehead | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Craniofacial
  name: Mandibular prognathia
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Mandibular prognathia
    term:
      id: HP:0000303
      label: Mandibular prognathia
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000303 | Mandibular prognathia | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Craniofacial
  name: Posteriorly rotated ears
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Posteriorly rotated ears
    term:
      id: HP:0000358
      label: Posteriorly rotated ears
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000358 | Posteriorly rotated ears | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Craniofacial
  name: Brachycephaly
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Brachycephaly
    term:
      id: HP:0000248
      label: Brachycephaly
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000248 | Brachycephaly | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Craniofacial
  name: Low anterior hairline
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Low anterior hairline
    term:
      id: HP:0000294
      label: Low anterior hairline
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000294 | Low anterior hairline | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Craniofacial
  name: Hypertelorism
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Hypertelorism
    term:
      id: HP:0000316
      label: Hypertelorism
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000316 | Hypertelorism | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Craniofacial
  name: Congenital craniofacial dysostosis
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Congenital craniofacial dysostosis
    term:
      id: HP:0008497
      label: Congenital craniofacial dysostosis
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0008497 | Congenital craniofacial dysostosis | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Craniofacial
  name: Coronal craniosynostosis
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Coronal craniosynostosis
    term:
      id: HP:0004440
      label: Coronal craniosynostosis
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0004440 | Coronal craniosynostosis | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Craniofacial
  name: Hypoplasia of the maxilla
  subtype: GCM type
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Hypoplasia of the maxilla
    term:
      id: HP:0000327
      label: Hypoplasia of the maxilla
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000327 | Hypoplasia of the maxilla | Frequent (79-30%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Craniofacial
  name: Abnormal skull morphology
  subtype: GCM type
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Abnormal skull morphology
    term:
      id: HP:0000929
      label: Abnormal skull morphology
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000929 | Abnormal skull morphology | Frequent (79-30%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Craniofacial
  name: Aplasia or hypoplasia of the nasal bone
  subtype: GCM type
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Aplasia/Hypoplasia of the nasal bone
    term:
      id: HP:0010940
      label: Aplasia/Hypoplasia of the nasal bone
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0010940 | Aplasia/Hypoplasia of the nasal bone | Frequent (79-30%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Dermatologic
  name: Cutis laxa
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Cutis laxa
    term:
      id: HP:0000973
      label: Cutis laxa
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000973 | Cutis laxa | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Dermatologic
  name: Redundant skin
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Redundant skin
    term:
      id: HP:0001582
      label: Redundant skin
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001582 | Redundant skin | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Dermatologic
  name: Prematurely aged appearance
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Prematurely aged appearance
    term:
      id: HP:0007495
      label: Prematurely aged appearance
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0007495 | Prematurely aged appearance | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Dermatologic
  name: Reduced subcutaneous adipose tissue
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Reduced subcutaneous adipose tissue
    term:
      id: HP:0003758
      label: Reduced subcutaneous adipose tissue
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003758 | Reduced subcutaneous adipose tissue | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Dermatologic
  name: Lipoatrophy
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Lipoatrophy
    term:
      id: HP:0100578
      label: Lipoatrophy
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100578 | Lipoatrophy | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Dermatologic
  name: Shagreen patch
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Shagreen patch
    term:
      id: HP:0009721
      label: Shagreen patch
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0009721 | Shagreen patch | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hair and nails
  name: Generalized hirsutism
  frequency: VERY_FREQUENT
  subtypes:
  - Petty type
  - GCM type
  phenotype_term:
    preferred_term: Generalized hirsutism
    term:
      id: HP:0002230
      label: Generalized hirsutism
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002230 | Generalized hirsutism | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002230 | Generalized hirsutism | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Hair and nails
  name: Abnormality of the hair
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormality of the hair
    term:
      id: HP:0001595
      label: Abnormal hair morphology
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001595 | Abnormality of the hair | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hair and nails
  name: Abnormality of the nail
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormality of the nail
    term:
      id: HP:0001597
      label: Abnormal nail morphology
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001597 | Abnormality of the nail | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hair and nails
  name: Brittle hair
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Brittle hair
    term:
      id: HP:0002299
      label: Brittle hair
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002299 | Brittle hair | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hair and nails
  name: Sparse hair
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Sparse hair
    term:
      id: HP:0008070
      label: Sparse hair
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0008070 | Sparse hair | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hair and nails
  name: Thick eyebrow
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Thick eyebrow
    term:
      id: HP:0000574
      label: Thick eyebrow
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000574 | Thick eyebrow | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hair and nails
  name: Long eyelashes in irregular rows
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Long eyelashes in irregular rows
    term:
      id: HP:0007740
      label: Long eyelashes in irregular rows
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0007740 | Long eyelashes in irregular rows | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hair and nails
  name: Coarse hair
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Coarse hair
    term:
      id: HP:0002208
      label: Coarse hair
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002208 | Coarse hair | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Ocular
  name: Strabismus
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Strabismus
    term:
      id: HP:0000486
      label: Strabismus
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000486 | Strabismus | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Ocular
  name: Epicanthus
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Epicanthus
    term:
      id: HP:0000286
      label: Epicanthus
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000286 | Epicanthus | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Ocular
  name: Abnormality of the eye
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormality of the eye
    term:
      id: HP:0000478
      label: Abnormality of the eye
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000478 | Abnormality of the eye | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Ocular
  name: Abnormal eyelid morphology
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormal eyelid morphology
    term:
      id: HP:0000492
      label: Abnormal eyelid morphology
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000492 | Abnormal eyelid morphology | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Ocular
  name: Abnormality of vision
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormality of vision
    term:
      id: HP:0000504
      label: Abnormality of vision
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000504 | Abnormality of vision | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Ocular
  name: Nystagmus
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Nystagmus
    term:
      id: HP:0000639
      label: Nystagmus
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000639 | Nystagmus | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Ocular
  name: Astigmatism
  subtype: GCM type
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Astigmatism
    term:
      id: HP:0000483
      label: Astigmatism
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000483 | Astigmatism | Frequent (79-30%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Ocular
  name: Sclerocornea
  subtype: GCM type
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Sclerocornea
    term:
      id: HP:0000647
      label: Sclerocornea
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000647 | Sclerocornea | Frequent (79-30%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Ocular
  name: Upper eyelid coloboma
  subtype: GCM type
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Upper eyelid coloboma
    term:
      id: HP:0000636
      label: Upper eyelid coloboma
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000636 | Upper eyelid coloboma | Occasional (29-5%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Dental
  name: Tooth agenesis
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Tooth agenesis
    term:
      id: HP:0009804
      label: Tooth agenesis
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0009804 | Tooth agenesis | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Dental
  name: Abnormality of the dentition
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormality of the dentition
    term:
      id: HP:0000164
      label: Abnormality of the dentition
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000164 | Abnormality of the dentition | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Dental
  name: Oligodontia
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Oligodontia
    term:
      id: HP:0000677
      label: Oligodontia
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000677 | Oligodontia | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Musculoskeletal
  name: Short distal phalanx of finger
  frequency: VERY_FREQUENT
  subtypes:
  - Petty type
  - GCM type
  phenotype_term:
    preferred_term: Short distal phalanx of finger
    term:
      id: HP:0009882
      label: Short distal phalanx of finger
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0009882 | Short distal phalanx of finger | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0009882 | Short distal phalanx of finger | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Musculoskeletal
  name: Decreased skull ossification
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Decreased skull ossification
    term:
      id: HP:0004331
      label: Decreased skull ossification
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0004331 | Decreased skull ossification | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Musculoskeletal
  name: Abnormal foot morphology
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormal foot morphology
    term:
      id: HP:0001760
      label: Abnormal foot morphology
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001760 | Abnormal foot morphology | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Musculoskeletal
  name: Abnormal metacarpal morphology
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormal metacarpal morphology
    term:
      id: HP:0005916
      label: Abnormal metacarpal morphology
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0005916 | Abnormal metacarpal morphology | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Dermatoglyphics
  name: Abnormal dermatoglyphics
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Abnormal dermatoglyphics
    term:
      id: HP:0007477
      label: Abnormal dermatoglyphics
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0007477 | Abnormal dermatoglyphics | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hernia
  name: Umbilical hernia in Petty type
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Umbilical hernia
    term:
      id: HP:0001537
      label: Umbilical hernia
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001537 | Umbilical hernia | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Hernia
  name: Umbilical hernia in GCM type
  subtype: GCM type
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Umbilical hernia
    term:
      id: HP:0001537
      label: Umbilical hernia
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001537 | Umbilical hernia | Frequent (79-30%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Cardiovascular
  name: Patent ductus arteriosus
  subtype: GCM type
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Patent ductus arteriosus
    term:
      id: HP:0001643
      label: Patent ductus arteriosus
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001643 | Patent ductus arteriosus | Frequent (79-30%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Auditory
  name: Conductive hearing impairment
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Conductive hearing impairment
    term:
      id: HP:0000405
      label: Conductive hearing impairment
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000405 | Conductive hearing impairment | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Neurodevelopmental
  name: Mild intellectual disability
  subtype: GCM type
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Intellectual disability, mild
    term:
      id: HP:0001256
      label: Mild intellectual disability
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001256 | Intellectual disability, mild | Occasional (29-5%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
- category: Facial
  name: Everted lower lip vermilion
  subtype: Petty type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Everted lower lip vermilion
    term:
      id: HP:0000232
      label: Everted lower lip vermilion
  evidence:
  - reference: ORPHA:2963
    reference_title: "Progeroid syndrome, Petty type (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0000232 | Everted lower lip vermilion | Very frequent (99-80%)"
    explanation: Orphanet provides the Petty type phenotype association and frequency band.
- category: Facial
  name: Underdeveloped supraorbital ridges
  subtype: GCM type
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Underdeveloped supraorbital ridges
    term:
      id: HP:0009891
      label: Underdeveloped supraorbital ridges
  evidence:
  - reference: ORPHA:2095
    reference_title: "Gorlin-Chaudhry-Moss syndrome (Orphanet structured-database record)"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0009891 | Underdeveloped supraorbital ridges | Very frequent (99-80%)"
    explanation: Orphanet provides the GCM phenotype association and frequency band.
diagnosis:
- name: SLC25A24 molecular genetic testing
  description: >-
    Molecular genetic testing establishes the diagnosis in an individual with
    suggestive clinical findings and a heterozygous pathogenic SLC25A24 variant.
  diagnosis_term:
    preferred_term: genetic testing
    term:
      id: MAXO:0000127
      label: genetic testing
  evidence:
  - reference: PMID:35679445
    reference_title: SLC25A24 Fontaine Progeroid Syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "established in a proband with suggestive findings and a heterozygous pathogenic variant in SLC25A24 identified by molecular genetic testing."
    explanation: GeneReviews supports SLC25A24 molecular testing as diagnostic.
- name: Prenatal exome or genome sequencing
  description: >-
    Exome or genome sequencing can support prenatal or postmortem diagnosis
    when fetal polymalformations occur with normal karyotype and array CGH.
  diagnosis_term:
    preferred_term: genetic testing
    term:
      id: MAXO:0000127
      label: genetic testing
  evidence:
  - reference: PMID:38980211
    reference_title: "Prenatal diagnosis of SLC25A24 Fontaine progeroid syndrome: description of the fetal phenotype, genotype and detection of parental mosaicism."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "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"
    explanation: Prenatal series supports genome-scale sequencing in the diagnostic setting.
treatments:
- name: Multidisciplinary symptomatic management
  description: >-
    Management is largely symptomatic and coordinated across craniofacial,
    cardiology, pulmonology, gastroenterology, otolaryngology, genetics, and
    developmental supports according to the manifestations present.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  target_phenotypes:
  - preferred_term: Craniosynostosis
    term:
      id: HP:0001363
      label: Craniosynostosis
  - preferred_term: Patent ductus arteriosus
    term:
      id: HP:0001643
      label: Patent ductus arteriosus
  evidence:
  - reference: PMID:35679445
    reference_title: SLC25A24 Fontaine Progeroid Syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Management, which is largely symptomatic, may be performed by specialists in multiple disciplines"
    explanation: GeneReviews supports symptomatic multidisciplinary care.
- name: Routine clinical surveillance
  description: >-
    Ongoing surveillance assesses emerging manifestations and treatment
    response, including development, cranial, cardiovascular, pulmonary,
    gastrointestinal, and other system-specific complications.
  treatment_term:
    preferred_term: clinical assessment
    term:
      id: MAXO:0000487
      label: clinical assessment
  evidence:
  - reference: PMID:35679445
    reference_title: SLC25A24 Fontaine Progeroid Syndrome.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Routine evaluation to assess development of new manifestations and response to ongoing management."
    explanation: GeneReviews supports surveillance through routine clinical assessment.
notes: >-
  Orphanet retains separate historical subtype records for Petty type
  (ORPHA:2963) and Gorlin-Chaudhry-Moss syndrome (ORPHA:2095). Molecular
  literature supports integrating these presentations under SLC25A24 Fontaine
  progeroid syndrome. ORPHA:2095 still lists autosomal recessive inheritance,
  but this entry follows current molecular evidence and GeneReviews in modeling
  the SLC25A24 syndrome as autosomal dominant, usually de novo.
📚

References & Deep Research

References

9
ORPHA:2963
Progeroid syndrome, Petty type
1 finding
Orphanet maps the Petty type subtype exactly to MONDO:0012853 and provides autosomal dominant inheritance, SLC25A24, epidemiology, and HPO phenotype rows.
"MONDO:0012853 | Exact"
ORPHA:2095
Gorlin-Chaudhry-Moss syndrome
1 finding
Orphanet records the historical Gorlin-Chaudhry-Moss subtype with SLC25A24 and structured HPO phenotype rows.
"SLC25A24 | solute carrier family 25 member 24 | hgnc:20662 | Disease-causing germline mutation(s) in"
ORPHA:697101
Fontaine progeroid syndrome
1 finding
Orphanet records Fontaine progeroid syndrome as a disease-level record with an exact OMIM mapping.
"OMIM:612289 | Exact"
PMID:35679445
SLC25A24 Fontaine Progeroid Syndrome.
1 finding
GeneReviews summarizes Fontaine progeroid syndrome clinical features, molecular diagnosis, management, surveillance, and autosomal dominant mostly de novo inheritance.
"SLC25A24 Fontaine progeroid syndrome is a multisystem connective tissue disorder"
PMID:29100093
De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction.
1 finding
A GCMS cohort identified recurrent de novo SLC25A24 variants and showed mitochondrial swelling, low matrix ATP, oxidative-stress sensitivity, and gain of pathological function.
"These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations."
PMID:29100094
De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise.
1 finding
A second discovery series named Fontaine syndrome and linked codon 217 SLC25A24 variants to impaired ATP-Mg/phosphate transport dynamics and abnormal mitochondrial energy metabolism.
"Our findings identify SLC25A24 mutations affecting codon 217 as the underlying genetic cause of human progeroid Fontaine syndrome."
PMID:31775791
A 9-year-old Korean girl with Fontaine progeroid syndrome: a case report with further phenotypical delineation and description of clinical course during long-term follow-up.
1 finding
Long-term case follow-up supports integrating GCMS and FFS under Fontaine progeroid syndrome and documents typical clinical features with a de novo SLC25A24 variant.
"it has been proposed recently that they be integrated into a single disorder under the name of Fontaine progeroid syndrome (FPS)."
PMID:38980211
Prenatal diagnosis of SLC25A24 Fontaine progeroid syndrome: description of the fetal phenotype, genotype and detection of parental mosaicism.
1 finding
Prenatal cases support the fetal phenotype, exome/genome diagnostic utility, and possible parental mosaicism in recurrence risk.
"paternal SLC25A24 mosaicism was detected in one case."
PMID:41271664
Fontaine progeroid syndrome with neonatal mitochondrial disease.
1 finding
A neonatal case directly diagnosed mitochondrial disease in Fontaine progeroid syndrome with decreased respiratory chain enzyme activity.
"decreased activity of mitochondrial respiratory chain enzyme activity."

Deep Research

1
Fontaine Progeroid Syndrome fallback research ▸

Fontaine Progeroid Syndrome fallback research

Scope

This fallback artifact supports the initial direct-Orpha curation of Fontaine_Progeroid_Syndrome while provider-based deep research is attempted with bounded timeouts. The entry focuses on the MONDO:0012853 / SLC25A24 Fontaine progeroid syndrome root and its Orphanet historical subtype records: ORPHA:697101, ORPHA:2963, and ORPHA:2095.

Structured sources

  • ORPHA:697101: disease-level Fontaine progeroid syndrome record with exact OMIM:612289 mapping.
  • ORPHA:2963: Progeroid syndrome, Petty type; includes exact MONDO:0012853, autosomal dominant inheritance, SLC25A24 gene association, epidemiology, and HPO phenotype-frequency rows.
  • ORPHA:2095: Gorlin-Chaudhry-Moss syndrome; includes historical GCM synonyms, SLC25A24 gene association, epidemiology, and HPO phenotype-frequency rows.

Primary literature used

  • PMID:35679445 GeneReviews, "SLC25A24 Fontaine Progeroid Syndrome." Used for the current clinical definition, molecular diagnosis, autosomal dominant usually de novo inheritance, management, surveillance, and recurrence-risk counseling.
  • PMID:29100093 Ehmke et al. 2017, AJHG. Used for recurrent de novo SLC25A24 variants, mitochondrial inner membrane ATP-Mg/Pi carrier function, patient-fibroblast mitochondrial swelling, low matrix ATP, oxidative-stress sensitivity, gain-of-pathological-function interpretation, and linkage to skeletal/connective-tissue development.
  • PMID:29100094 Writzl et al. 2017, AJHG. Used for the Fontaine syndrome name, recurrent codon 217 SLC25A24 variants, ATP-Mg/phosphate exchange, substrate cavity and transporter-dynamics modeling, altered mitochondrial morphology, decreased proliferation, increased membrane potential, decreased ATP-linked oxygen consumption, and impaired mitochondrial ATP synthesis.
  • PMID:31775791 Ryu et al. 2019. Used for integration of GCMS and Fontaine-Farriaux syndrome under Fontaine progeroid syndrome and long-term clinical follow-up.
  • PMID:38980211 Pannier et al. 2024. Used for prenatal diagnosis, fetal phenotype extension, exome/genome diagnostic utility, and paternal SLC25A24 mosaicism.
  • PMID:36093452 Lally et al. 2022. Used for early-lethality summary.
  • PMID:41271664 Riko et al. 2025. Used for neonatal mitochondrial disease and decreased mitochondrial respiratory chain enzyme activity.
  • PMID:23686885 Rosti et al. 2013. Background historical GCM phenotype review; not required for the primary mechanism graph because Orphanet and SLC25A24 molecular evidence cover the structured claims.

Literature-scope notes

PubMed searches were run for "Fontaine progeroid syndrome", "Gorlin-Chaudhry-Moss syndrome", "Petty Laxova Wiedemann syndrome", and "SLC25A24 progeroid". The priority curation evidence was selected from GeneReviews, the two 2017 AJHG molecular discovery papers, Orphanet structured records, and later case reports that add prenatal, long-term follow-up, lethality, mosaicism, or mitochondrial-disease information.

Provider attempts

  • 2026-05-07: timeout 75s just research-disorder falcon Fontaine_Progeroid_Syndrome timed out with signal 15 before producing an artifact.
  • 2026-05-07: timeout 75s just research-disorder openai Fontaine_Progeroid_Syndrome timed out with signal 15 before producing an artifact.

Because both bounded provider attempts failed to return promptly, this curation proceeds from the PubMed, GeneReviews, and Orphanet evidence above.