Cutis laxa, fat pads and retinopathy due to ALDH18A1 mutation and review of the literature.
Autosomal recessive cutis laxa (ARCL) is a connective tissue disorder characterized by wrinkled, inelastic skin, frequently associated with a neurologic involvement and multisystem disease. Next generation sequencing was performed in genetically unsolved patients with progeroid features, neurological and eye involvement to assess the underlying etiology. We describe an 6 month old child, diagnosed with a novel, homozygous nonsense mutation c.2339T>C in exon 18 of the ALDH18A1 gene, and reviewed all reported P5CS patients. So far 10 patients were described with mutations in ALDH18A1. Features of our patient that have been described in literature included cutis laxa on hands and feet, visible veins on thorax and abdomen, joint laxity, failure to thrive, short stature, microcephaly, and severe developmental and speech delay. Furthermore, abnormal fat distribution, retinal abnormalities, undescended testis, and retinitis pigmentosa have never been described in ALDH18A1. Some features described as unique in ALDH18A1 have been observed in PYCR1 patients, thus suggesting that the phenotypic overlap is higher than previously shown. In conclusion, the clinical phenotype caused by ALDH18A1 mutations is diverse, with variable degree of progeria in children, but always in association with neurologic disease. We suggest genetic testing for possible ALDH18A1 mutations in all patients with progeroid features, like wrinkled or parchment-like skin, abnormal growth, especially with central nervous system involvement and microcephaly.
Hayward Genetics Center, Tulane University Medical School, 1430 Tulane Ave, New Orleans, LA 70112, USA; Laboratory of Genetic, Metabolic and Endocrine Diseases, Radboud University Medical Centre Nijmegen, The Netherlands; Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands.
David F G J
DF
Wolthuis
Hayward Genetics Center, Tulane University Medical School, 1430 Tulane Ave, New Orleans, LA 70112, USA; Laboratory of Genetic, Metabolic and Endocrine Diseases, Radboud University Medical Centre Nijmegen, The Netherlands; Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands.
Ellyze
E
van Asbeck
Hayward Genetics Center, Tulane University Medical School, 1430 Tulane Ave, New Orleans, LA 70112, USA; Laboratory of Genetic, Metabolic and Endocrine Diseases, Radboud University Medical Centre Nijmegen, The Netherlands; Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands.
Miski
M
Mohamed
Hayward Genetics Center, Tulane University Medical School, 1430 Tulane Ave, New Orleans, LA 70112, USA; Laboratory of Genetic, Metabolic and Endocrine Diseases, Radboud University Medical Centre Nijmegen, The Netherlands; Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands.
Thatjana
T
Gardeitchik
Regional Medical Genetics Center, N.Y. Medical College, Valhalla, USA.
Elizabeth R
ER
Lim-Melia
Laboratory of Genetic, Metabolic and Endocrine Diseases, Radboud University Medical Centre Nijmegen, The Netherlands.
Ron A
RA
Wevers
Hayward Genetics Center, Tulane University Medical School, 1430 Tulane Ave, New Orleans, LA 70112, USA; Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands. Electronic address: emoravakozicz@tulane.edu.
Eva
E
Morava
D000273:Adipose Tissue / Q000473:pathology*; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000080924:Aldehyde Dehydrogenase 1 Family; D002675:Child, Preschool; D003483:Cutis Laxa / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D050697:Retinal Dehydrogenase; D012164:Retinal Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology
D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
ALDH18A1; Abnormal fat distribution; Cutis laxa; Retinopathy