title: Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica.
abstract: Cutis laxa is a heterogeneous condition characterized by redundant, sagging, inelastic, and wrinkled skin. The inherited forms of this disease are rare and can have autosomal dominant, autosomal recessive, or X-linked inheritance. Three of the autosomal recessive cutis laxa syndromes, namely cutis laxa IIA (ARCL2A), cutis laxa IIB (ARCL2B), and geroderma osteodysplastica (GO), have very similar clinical features, complicating accurate diagnosis. Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. These conditions also share additional features, such as short stature, hypotonia, and congenital hip dislocation, but the severity and frequency of these findings are variable in each of these cutis laxa syndromes. The characteristic features for ARCL2A are abnormal isoelectric focusing and facial features, including downslanting palpebral fissures and a long philtrum. Rather, the clinical phenotype of ARCL2B includes severe wrinkling of the dorsum of the hands and feet, wormian bones, athetoid movements, lipodystrophy, cataract and corneal clouding, a thin triangular face, and a pinched nose. Normal cognition and osteopenia leading to pathological fractures, maxillary hypoplasia, and oblique furrowing from the outer canthus to the lateral border of the supraorbital ridge are discriminative features for GO. Here we present 10 Iranian patients who were initially diagnosed clinically using the respective features of each cutis laxa syndrome. Each patient's clinical diagnosis was then confirmed with molecular investigation of the responsible gene. Review of the clinical features from the cases reported from the literature also supports our conclusions.
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, #2, 4th Street, Hasan Seyf Street, Sanat Square, Tehran 14667-13713, Iran. arianakariminejad@yahoo.com.
authors.forename: Ariana
authors.initials: A
authors.lastname: Kariminejad
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, #2, 4th Street, Hasan Seyf Street, Sanat Square, Tehran 14667-13713, Iran. afroozan@yahoo.com.
authors.forename: Fariba
authors.initials: F
authors.lastname: Afroozan
authors.affiliation: Kariminejad-Najmabadi Pathology & Genetics Center, #2, 4th Street, Hasan Seyf Street, Sanat Square, Tehran 14667-13713, Iran. b_bzwr@yahoo.com.
authors.forename: Bita
authors.initials: B
authors.lastname: Bozorgmehr
authors.affiliation: Department of Dermatopathology, Razi Dermatology Hospital, Tehran University of Medical Sciences, Tehran 14167-53955, Iran. dermpath101@gmail.com.|Department of Pathology, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran 14197-33141, Iran. dermpath101@gmail.com.
authors.forename: Alireza
authors.initials: A
authors.lastname: Ghanadan
authors.affiliation: Clinical Genetics Division, Mofid Children's Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 15514-15468, Iran. susanakbaroghli@yahoo.com.
authors.forename: Susan
authors.initials: S
authors.lastname: Akbaroghli
authors.affiliation: Genetic Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran 19857-13834, Iran. hrkhkh@yahoo.com.
authors.forename: Hamid Reza
authors.initials: HR
authors.lastname: Khorram Khorshid
authors.affiliation: Mashhad Medical Genetic Counseling Center, Social Welfare and Rehabilitation Organization, Mashhad 91767-61999, Iran. mojahedi1381@yahoo.com.
authors.forename: Faezeh
authors.initials: F
authors.lastname: Mojahedi
authors.affiliation: Division of Pediatric Endocrinology and Inherited Metabolic Disorders, Department of Pediatrics, Tehran University of Medical Sciences, Tehran 14197-33141, Iran. arset59@yahoo.com.
authors.forename: Aria
authors.initials: A
authors.lastname: Setoodeh
authors.affiliation: Institute of Medical Biology, A*STAR, Singapore 138648, Singapore. abigail.loh@reversade.com.
authors.forename: Abigail
authors.initials: A
authors.lastname: Loh
authors.affiliation: Institute of Medical Biology, A*STAR, Singapore 138648, Singapore. t_yuxuan@yahoo.com.sg.
authors.forename: Yu Xuan
authors.initials: YX
authors.lastname: Tan
authors.affiliation: Institute of Medical Biology, A*STAR, Singapore 138648, Singapore. nathalie.escande@reversade.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Escande-Beillard
authors.affiliation: Center for Metabolic Diseases, Department of Pediatrics, University Hospitals Leuven, Leuven 3000, Belgium. Fransiska.Malfait@UGent.be.
authors.forename: Fransiska
authors.initials: F
authors.lastname: Malfait
authors.affiliation: Institute of Medical Biology, A*STAR, Singapore 138648, Singapore. bruno@reversade.com.
authors.forename: Bruno
authors.initials: B
authors.lastname: Reversade
authors.affiliation: Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, Gelderland 9102-6500, The Netherlands. Thatjana.Gardeitchik@radboudumc.nl.
authors.forename: Thatjana
authors.initials: T
authors.lastname: Gardeitchik
authors.affiliation: Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, Gelderland 9102-6500, The Netherlands. emoravakozicz@tulane.edu.|Hayward Genetics Center, Tulane University Medical School, New Orleans, LA 70112, USA. emoravakozicz@tulane.edu.
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
mesh_terms: D000328:Adult; D001847:Bone Diseases / Q000151:congenital* / Q000175:diagnosis; D002648:Child; D002675:Child, Preschool; D003483:Cutis Laxa / Q000175:diagnosis*; D003937:Diagnosis, Differential; D004392:Dwarfism / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D012873:Skin Diseases, Genetic / Q000175:diagnosis*; D013577:Syndrome
keywords: ATPase, H+ transporting lysosomal V0 subunit A2 (ATP6V0A2); GOLGIN, RAB6-INTERACTING (GORAB); Pyrroline-5-carboxylate reductase 1 (PYCR1); autosomal recessive cutis laxa 2A; autosomal recessive cutis laxa 2B; geroderma osteodysplastica