Autosomal Recessive Cutis Laxa Type I (ARCL1)

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Disease Ontology 12 DOID:0070144 MeSH 44 C562628 SNOMED-CT 67 254222002 ICD10 via Orphanet 33 Q82.8

UMLS via Orphanet 71 C0268351 C0432336 Orphanet 58 ORPHA90349 SNOMED-CT via HPO 68 128601007 157265008 197811007 197927001 199612005 201093004 22033007 22640007 228156007 234119001 246815009 247578003 248200007 253631001 268029009 268185002 27911000 297957009 298203008 32003007 36118008 367403001 396232000 398206004 398302004 409623005 42343007 45816000 699014000 8114009 84114007 87433001 90531003 90539001 91138005 more UMLS 70 C0268351 C0432336

GARD : ²⁰ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 90349 Definition A generalized connective tissue disorder characterized by the association of wrinkled, redundant and sagging inelastic skin with severe systemic manifestations (lung atelectesias and emphysema, vascular anomalies, and gastrointestinal and genitourinary tract diverticuli). Epidemiology The prevalence of ARCL1 is unknown but around 60 cases have been reported in the literature so far. Clinical description The skin manifestations affect the whole body and are usually recognizable from birth. The excessive lax skin is particularly prominent around the axillae, groins and neck and on the face (giving patients an aged appearance with eyelid ptosis and drooping cheeks). Pulmonary emphysema develops early in life (during the neonatal period or by early childhood), often leading to respiratory failure. Common vascular anomalies include arterial aneurysms, fibromuscular artery dysplasia and stenosis leading to progressive heart failure. Genitourinary tract diverticuli lead to vesicoureteral reflux and recurrent infections. Less frequent findings include late closure of the fontanel, joint laxity, hip dislocation, inguinal hernia, arachnodactyly, bone fragility, vascular tortuosity and aortic aneurysm. Intelligence is normal. Etiology ARCL1 is genetically heterogeneous and, although the etiology remains unknown in the majority of cases, mutations have been identified in some patients in the FBLN5 (14q31) and EFEMP2 (11q13) genes, encoding the extracellular matrix proteins fibulin-5 and EGF-containing fibulin-like extracellular matrix protein 2 (Fibulin-4), respectively. Arachnodactyly, bone fragility, vascular tortuosity and aortic aneurysms are common findings in patients carrying EFEMP2 mutations. Diagnostic methods Detailed clinical evaluation and histological studies of skin biopsies (revealing a moth-eaten appearance, abnormal elastin fiber branching and lose microfibrils associated with reduced elastin synthesis) are usually diagnostic in ARCL1. Molecular testing, available on a research basis only, may confirm the diagnosis in carriers of FBLN5 and EFEMP2 mutations. Differential diagnosis The differential diagnosis should include other forms of CL ( autosomal recessive type 2, autosomal dominant and X-lined CL) and related syndromes (gerodermia osteodysplastica, Cantu syndrome, wrinkly skin syndrome and De Barsy syndrome), together with the Ehlers-Danlos syndromes and Costello syndrome (see these terms). Genetic counseling Genetic counseling should be provided to affected families and prenatal diagnosis through molecular testing is feasible for families in which the disease-causing mutation has been identified. Management and treatment There are no effective therapeutic strategies available for ARCL1. Care should be multidisciplinary with symptomatic treatment of pulmonary emphysema, prophylactic therapy for infections and hernia repair. Prognosis The disease course in ARCL1 is severe, with most patients dying in childhood from cardiac or respiratory failure.

MalaCards based summary : Autosomal Recessive Cutis Laxa Type I, also known as cutis laxa, autosomal recessive, type i, is related to cutis laxa, autosomal recessive, type iiia and cutis laxa, autosomal recessive, type iid. An important gene associated with Autosomal Recessive Cutis Laxa Type I is EFEMP2 (EGF Containing Fibulin Extracellular Matrix Protein 2), and among its related pathways/superpathways are ERK Signaling and PAK Pathway. Affiliated tissues include skin, eye and heart, and related phenotypes are emphysema and redundant skin

Disease Ontology : ¹² A cutis laxa characterized by wrinkled, redundant and sagging inelastic skin and severe systemic manifestations particulary in the lungs, vasculature, and gastrointestinal and genitourinary systems.

Search Clinical Trials , NIH Clinical Center for Autosomal Recessive Cutis Laxa Type I

Search GEO for disease gene expression data for Autosomal Recessive Cutis Laxa Type I.