Gorlin-Chaudhry-Moss syndrome (GCMS) is a rare disorder consisting of craniofacial dysostosis, hypertrichosis, underdeveloped genitalia, and ocular and dental anomalies. Recently, GCMS has been reclassified together with Fontaine syndrome as Fontaine progeroid syndrome (FPS), after a common genetic basis was found. It was previously thought that GCMS/FPS was not associated with aortopathy, but in recent years 3 patients with aortic disease have been described. We describe the fourth case, who is the oldest patient with GCMS/FPS reported in the medical literature: a 45-year-old patient who presented with acute aortic dissection. We therefore recommend screening patients previously diagnosed with GCMS/FPS for aortic pathology to aid early detection and avoid patient presentation in an acute setting.

Gorlin-Chaudhry-Moss syndrome (GCMS) and Fontaine-Farriaux syndrome (FFS) are extremely rare genetic disorders that share similar clinical manifestations. Because a de novo missense mutation of the solute carrier family 25 member 24 (SLC25A24) gene was suggested to be the common genetic basis of both syndromes, it has been proposed recently that they be integrated into a single disorder under the name of Fontaine progeroid syndrome (FPS). A 9-year-old Korean girl presented with typical clinical features of FPS. She had generalized loose skin with decreased subcutaneous fat, skin wrinkling on the forehead and limbs, skull deformities and a peculiar facial appearance with microphthalmia and midface hypoplasia, anomalies of the digits and nails, a large umbilical hernia and a nearly normal developmental outcome. She exhibited prenatal and postnatal growth retardation together with short stature, and records showed that her height and weight were invariably under - 2.0 SD from birth to the age of 10 years. SLC25A24 analysis revealed a heterozygous mutation reported previously, NM_013386:c.650G > A, p.[Arg217His]. After screening her family for the identified mutation, she was confirmed as being a de novo case of FPS caused by an SLC25A24 mutation. We describe a Korean girl with typical clinical findings of FPS and a de novo mutation in SLC25A24, as well as 10 years of clinical follow-up, including growth and developmental achievements.

We report the clinical and genetic findings in a 15-year-old Spanish boy presenting prenatal and postnatal growth retardation, reduced subcutaneous adipose tissue, premature skin wrinkling, sparse hair, short distal phalanges with small nails, umbilical hernia, wide anterior fontanel, and normal cognitive and motor development. Exome sequencing uncovered a heterozygous mutation in SLC25A24 (NM_013386: c.650G>A: p.R217H) that encodes for the calcium-binding mitochondrial carrier protein SCaMC-1. This gain-of-function variant has been previously associated with Fontaine syndrome and Gorlin-Chaudhry-Moss syndrome, two entities that show overlapping features, and have been recently subsumed under the name Fontaine progeroid syndrome (FPS; MIM: 612289) in OMIM. Here, we describe the first male patient with genetically confirmed FPS who survives at least until adolescence.

Gorlin-Chaudhry-Moss syndrome (GCMS) is a dysmorphic syndrome characterized by coronal craniosynostosis and severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, and short distal phalanges. Variable lipoatrophy and cutis laxa are the basis for a progeroid appearance. Using exome and genome sequencing, we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls diagnosed with GCMS. Two of the girls had pronounced neonatal progeroid features and were initially diagnosed with Wiedemann-Rautenstrauch syndrome. SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/Pi carrier. In fibroblasts from affected individuals, the mutated SLC25A24 showed normal stability. In contrast to control cells, the probands' cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H2O2). The same effect was observed after overexpression of the mutant cDNA. Under normal culture conditions, the mitochondrial membrane potential of the probands' fibroblasts was intact, whereas ATP content in the mitochondrial matrix was lower than that in control cells. However, upon H2O2 exposure, the membrane potential was significantly elevated in cells harboring the mutated SLC25A24. No reduction of mitochondrial DNA copy number was observed. These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations. Our results suggest that the SLC25A24 mutations induce a gain of pathological function and link mitochondrial ATP-Mg/Pi transport to the development of skeletal and connective tissue.

We report the case of a 7-month-old girl with atypical oculo-facio-cardio-dental syndrome (OFCD). A novel de novo pathogenic mutation in the BCL6 interacting co-repressor gene (BCOR) (c.4540C>T; p.Arg1514*), was identified on the X chromosome. This case expands the phenotype of OFCD as it is the first report of a case presenting with craniosynostois, temporal hypertrichosis, supraorbital grooving, and underdevelopment of the midface.