Cutis laxa, autosomal recessive type 1

Title

Other Names:

Cutis laxa, type 1; Cutis laxa, autosomal recessive

Categories:

Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases; Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases; Lung Diseases; Skin Diseases See More

This disease is grouped under:

Cutis laxa

Summary Summary

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.

Visit the Orphanet disease page for more resources.

Last updated: 1/1/2011

Symptoms Symptoms

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
Dermatochalasis	Baggy eyes Droopy eyelid skin Extra eyelid skin Redundant eyelid skin [ more ]	0010750
Emphysema		0002097
Fragmented elastic fibers in the dermis		0025167
Lack of skin elasticity		0100679
Redundant skin	Loose redundant skin Redundant skin folds Sagging, redundant skin [ more ]	0001582
30%-79% of people have these symptoms
Abnormal facial shape	Unusual facial appearance	0001999
Abnormal systemic arterial morphology		0011004
Abnormality of the cheek	Abnormality of the cheeks	0004426
Abnormality of the thoracic cavity		0045027
Congestive heart failure	Cardiac failure Cardiac failures Heart failure [ more ]	0001635
Inguinal hernia		0000023
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Joint laxity	Joint instability Lax joints Loose-jointedness Loosejointedness [ more ]	0001388
Joint subluxation		0032153
Motor delay		0001270
Pathologic fracture	Spontaneous fracture	0002756
Peripheral pulmonary artery stenosis	Narrowing of peripheral lung artery	0004969
Pneumothorax	Collapsed lung	0002107
Respiratory insufficiency	Respiratory impairment	0002093
5%-29% of people have these symptoms
Abnormal cardiac ventricular function		0030872
Abnormal skull morphology	Abnormality of the skull	0000929
Dilatation of the ventricular cavity		0006698
Hip dislocation	Dislocated hips Dislocation of hip [ more ]	0002827
Multiple bladder diverticula	Multiple pouches in bladder wall	0012619
Pyelonephritis		0012330
Pyloric stenosis		0002021
Recurrent pneumonia		0006532
Recurrent urinary tract infections	Frequent urinary tract infections Repeated bladder infections Repeated urinary tract infections Urinary tract infections Urinary tract infections, recurrent [ more ]	0000010
Small bowel diverticula		0002256
Supravalvular aortic stenosis		0004381
Urethral diverticulum		0008722
Vesicoureteral reflux		0000076
1%-4% of people have these symptoms
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Percent of people who have these symptoms is not available through HPO
Abnormality of the face	Abnormal face Facial abnormality [ more ]	0000271
Arachnodactyly	Long slender fingers Spider fingers [ more ]	0001166
Ascending tubular aorta aneurysm	Bulging of wall of large artery located above heart	0004970
Autosomal recessive inheritance		0000007
Bladder diverticulum		0000015
Congenital diaphragmatic hernia		0000776
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
Umbilical hernia		0001537
Vascular tortuosity	Twisted blood vessels	0004948

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Last updated: 2/1/2021

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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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Research Research

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.

Learn More 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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