Disease Profile

Cutis laxa, autosomal recessive type 1

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset

Infancy

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ICD-10

Q82.8

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

Cutis laxa, type 1; Cutis laxa, autosomal recessive

Categories

Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases;

Summary

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.

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.

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

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.