National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Cutis laxa, autosomal recessive type 1


Other Names:
Cutis laxa, type 1; Cutis laxa, autosomal recessive
Categories:
This disease is grouped under:
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

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.

Visit the Orphanet disease page for more resources.
Last updated: 1/1/2011

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Arterial fibromuscular dysplasia 0005313
Atelectasis
Partial or complete collapse of part or entire lung
0100750
Bladder diverticulum 0000015
Congenital diaphragmatic hernia 0000776
Emphysema 0002097
Premature skin wrinkling 0100678
Recurrent urinary tract infections
Frequent urinary tract infections
Repeated bladder infections
Repeated urinary tract infections
Urinary tract infections
Urinary tract infections, recurrent
[ more ] 		0000010
Redundant skin
Loose redundant skin
Redundant skin folds
Sagging, redundant skin
[ more ] 		0001582
Renal diverticulum 0100877
30%-79% of people have these symptoms
Aortic aneurysm
Bulge in wall of large artery that carries blood away from heart
0004942
Arterial stenosis
Narrowing of an artery
0100545
Delayed cranial suture closure 0000270
Full cheeks
Apple cheeks
Big cheeks
Increased size of cheeks
Large cheeks
[ more ] 		0000293
Ileus 0002595
Inguinal hernia 0000023
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Ptosis
Drooping upper eyelid
0000508
5%-29% of people have these symptoms
Arachnodactyly
Long slender fingers
Spider fingers
[ more ] 		0001166
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ] 		0011675
Bowel diverticulosis 0005222
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure
[ more ] 		0001635
Hypothyroidism
Underactive thyroid
0000821
Osteoporosis 0000939
Pulmonic stenosis
Narrowing of pulmonic valve
0001642
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures
[ more ] 		0002757
Respiratory distress
Breathing difficulties
Difficulty breathing
[ more ] 		0002098
Vesicoureteral reflux 0000076
Wormian bones
Extra bones within cranial sutures
0002645
Percent of people who have these symptoms is not available through HPO
Abnormality of the face
Abnormal face
Facial abnormality
[ more ] 		0000271
Ascending tubular aorta aneurysm
Bulging of wall of large artery located above heart
0004970
Autosomal recessive inheritance 0000007
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness
[ more ] 		0001388
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Oligohydramnios
Low levels of amniotic fluid
0001562
Overgrowth
General overgrowth
0001548
Pectus excavatum
Funnel chest
0000767
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
Supravalvular aortic stenosis 0004381
Umbilical hernia 0001537
Vascular tortuosity
Twisted blood vessels
0004948
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Last updated: 7/1/2020

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • Cutis Laxa Research Study
    University of Pittsburgh
    Dept. of Human Genetics
    A300 Crabtree Hall, GSPH
    130 De Soto Street
    Pittsburgh, PA 15261
    Telephone: 412-383-7369
    E-mail: cutislax@pitt.edu
    Website: http://www.cutislaxa.pitt.edu
    The Cutis Laxa Research Study is an ongoing project coordinated by the University of Pittsburgh. Their research focuses on identifying the genetic causes of cutis laxa in an effort to better understand the effect of gene mutations and develop new treatments. Use the provided contact information to learn more.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Cutis laxa, autosomal recessive type 1. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Cutis laxa, autosomal recessive type 1. Click on the link to view a sample search on this topic.

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