NIH Rare Diseases
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53
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 90349Disease definitionAutosomal recessive cutis laxa, type 1 (ARCL1) is 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).EpidemiologyThe prevalence of ARCL1 is unknown but around 60 cases have been reported in the literature so far.Clinical descriptionThe 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.EtiologyARCL1 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 methodsDetailed 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 diagnosisThe 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 counselingGenetic 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 treatmentThere 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.PrognosisThe disease course in ARCL1 is severe, with most patients dying in childhood from cardiac or respiratory failure.Visit the Orphanet disease page for more resources.
MalaCards based summary
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Autosomal Recessive Cutis Laxa Type I, also known as
cutis laxa, autosomal recessive, type i, is related to
cutis laxa, autosomal recessive, type ia and
cutis laxa, autosomal recessive, type ib. 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
Phospholipase-C Pathway. Affiliated tissues include
skin,
lung and
bone, and related phenotypes are
ptosis and
hypothyroidism
Disease Ontology
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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.
Rare circulatory system diseases
