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Cutis laxa type 1B
This condition primarily affects the skin, causing it to appear prematurely aged and saggy. It can also impact other body systems, including blood vessels, lungs, and the gastrointestinal tract. It is a genetic condition typically inherited in an autosomal recessive manner.
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Overview
Cutis laxa type 1B is a rare genetic condition that primarily affects the body's connective tissues. Connective tissues provide support, strength, and elasticity to many parts of the body, including the skin, blood vessels, and internal organs. In individuals with cutis laxa type 1B, these tissues are weaker than usual, leading to a range of symptoms. The most noticeable feature is typically loose, wrinkled skin that lacks elasticity and can give an aged appearance, even in childhood [PMID:24072837].
Beyond the skin, the condition can also affect other systems. These may include the cardiovascular system, leading to issues with blood vessels, or the respiratory system, potentially causing lung problems. The gastrointestinal tract can also be involved. Because of the broad impact on connective tissues, symptoms can vary significantly among affected individuals, even within the same family [PMID:24072837].
Symptoms & clinical features
The hallmark symptom of cutis laxa type 1B is loose, sagging skin that hangs in folds, particularly prominent on the face, neck, and trunk [PMID:24072837]. This skin often appears thinner and less elastic than typical skin, contributing to a prematurely aged look. Unlike some other forms of cutis laxa, the skin changes in type 1B are often present from birth or develop early in life.
Beyond the skin, individuals may experience a variety of other symptoms due to the widespread nature of connective tissue involvement. These can include abnormalities of the large arteries, such as aortic dilation, which is a widening of the main artery carrying blood from the heart. Respiratory problems like emphysema-like changes in the lungs have also been reported. Some individuals might also have gastrointestinal issues. The severity and combination of these symptoms differ from person to person.
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Affected organs
Cutis laxa type 1B primarily affects organs and tissues rich in elastin, a protein vital for connective tissue elasticity. The skin is prominently affected, leading to its characteristic loose and inelastic appearance. Internal organs can also be involved, though the extent varies.
Key internal systems that may be impacted include the cardiovascular system, where large blood vessels like the aorta can be weakened. The respiratory system may also show changes, with reports of lung abnormalities. Additionally, the gastrointestinal tract can be affected, potentially leading to related complications.
Risks & severity
The severity of cutis laxa type 1B is variable, ranging from milder skin manifestations to significant systemic complications affecting multiple organ systems [PMID:24072837]. The major risks often relate to the involvement of internal organs, particularly the cardiovascular and respiratory systems. Issues such as arterial dilation or lung abnormalities can have serious implications and may require ongoing medical monitoring.
While the exact prevalence of cutis laxa type 1B is not well established due to its rare nature, the condition is considered congenital or appears early in life. The progressive nature of connective tissue weakening means that symptoms, particularly skin laxity, can become more noticeable with age. Careful clinical surveillance is often recommended to manage potential complications effectively.
Genetic causes
Cutis laxa type 1B is caused by pathogenic variants in the EFEMP2 gene. This gene provides instructions for making a protein called fibulin-4, which is crucial for the formation and maintenance of elastic fibres [PMID:24072837]. Elastic fibres are essential components of connective tissue, responsible for giving tissues like skin, blood vessels, and lungs their resilience and ability to stretch and recoil.
Pathogenic variants in EFEMP2 lead to errors in the production or function of fibulin-4. When normal fibulin-4 is not available or does not function correctly, the body cannot form strong, functional elastic fibres. This results in the weakened and fragmented connective tissue observed in individuals with cutis laxa type 1B, leading to the characteristic skin laxity and potential internal organ involvement [PMID:19363025].
- EFEMP2 EGF-like fibulin extracellular matrix protein 2
Inheritance pattern
Cutis laxa type 1B is inherited in an autosomal recessive manner. This means that an individual must inherit two altered copies of the EFEMP2 gene - one from each parent - to develop the condition. People who have only one altered copy of the EFEMP2 gene are called carriers. Carriers typically do not show symptoms of cutis laxa type 1B because their one working copy of the gene is usually sufficient to produce enough functional fibulin-4 protein.
If both parents are carriers of a pathogenic EFEMP2 variant, there is a 25% chance with each pregnancy that their child will inherit two altered copies and be affected by cutis laxa type 1B. There is a 50% chance the child will be a carrier, and a 25% chance the child will inherit two unaffected copies of the gene and will not be affected and not be a carrier.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Diagnosing cutis laxa type 1B typically begins with a clinical evaluation based on the characteristic physical features, especially the loose, inelastic skin. If cutis laxa is suspected, further investigations may be carried out to assess potential internal organ involvement, such as imaging of the heart and blood vessels or lung function tests. However, a definitive diagnosis relies on genetic testing.
Genetic testing to identify pathogenic variants in the EFEMP2 gene is performed via blood or saliva samples. This testing is often arranged through a clinical genetics service following a referral from a GP or specialist. In the UK, such testing falls under the NHS Genomic Medicine Service, sometimes guided by specific R-codes for rare disease diagnosis. Genetic testing can help confirm the diagnosis, distinguish between different types of cutis laxa, and inform reproductive planning.
Management & lifestyle
The management of cutis laxa type 1B focuses on addressing specific symptoms and potential complications, as there is currently no cure for the underlying genetic cause. Care is often multidisciplinary, involving various medical specialists depending on the affected organ systems. For skin laxity, cosmetic surgery may be considered in some cases, although the skin may become lax again over time.
Regular monitoring for cardiovascular and respiratory complications is vital. This may include regular echocardiograms to check the aorta and other blood vessels, and lung function tests. Any identified issues would be managed according to standard clinical guidelines. Genetic counsellors can provide support and information to individuals and families regarding the condition's inheritance and implications for family planning.
UK care pathway
In the UK, individuals suspected of having a rare genetic condition like cutis laxa type 1B are typically referred to a Clinical Genetics service. This referral can come from a GP or another specialist. The Clinical Genetics team, which may include genetic consultants and genetic counsellors, will assess the clinical features and family history. If genetic testing is deemed appropriate, it will be arranged through the NHS Genomic Medicine Service.
The testing may be facilitated by specific R-codes, which are used to define the diagnostic tests available. Following a confirmed diagnosis, individuals and their families will receive ongoing support and information from a genetic counsellor. They will also be guided to relevant specialists for the management of specific symptoms, in line with NHS care pathways.
Frequently asked questions
Is cutis laxa type 1B contagious?
No, cutis laxa type 1B is a genetic condition caused by changes in a person's DNA, so it cannot be caught from another person or spread like an infection.
How common is cutis laxa type 1B?
Cutis laxa type 1B is considered a very rare condition. The exact number of people affected is not precisely known, but it is encountered infrequently in clinical practice.
Can cutis laxa type 1B be cured?
Currently, there is no cure for the underlying genetic cause of cutis laxa type 1B. Management focuses on treating the specific symptoms and complications that arise.
What kind of doctors treat cutis laxa type 1B?
Management often involves a team of specialists. This may include dermatologists for skin concerns, cardiologists for heart and blood vessel issues, pulmonologists for lung problems, and clinical geneticists for genetic counselling and overall coordination of care.
Will my children inherit cutis laxa type 1B if I have it?
Cutis laxa type 1B is inherited in an autosomal recessive pattern. This means if you have the condition, you would pass on one altered copy of the EFEMP2 gene to all your children. Your children would only develop the condition if they also inherited an altered copy from the other parent. Genetic counselling is recommended to discuss specific risks.
References
- Adam MP, Bick S, Mirzaa GM. EFEMP2-Related Cutis Laxa. 1993. PMID: 21563328
- Adamo CS, Beyens A, Schiavinato A. EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis. American journal of human genetics. 2022. PMID: 36351433
- Letard P, Schepers D, Albuisson J. Severe Phenotype of Cutis Laxa Type 1B with Antenatal Signs due to a Novel Homozygous Nonsense Mutation in EFEMP2. Molecular syndromology. 2018. PMID: 30140196
- Halabi CM, Broekelmann TJ, Lin M. Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not muscular arteries. Science advances. 2017. PMID: 28508064
- Sülü A, Başpınar O, Şahin DA. Giant aortic aneurysm due to fibulin- 4 deficiency: case series. Turk pediatri arsivi. 2019. PMID: 31384147
- Ouyang L, Yang F, Duan H. Case Report and literature review: Delayed diagnosis of ARCL1B due to a newly reported homozygous mutation c.464A>C p. (Tyr155Ser) in the EFEMP2 gene. Frontiers in genetics. 2024. PMID: 39764439
- Hebson C, Coleman K, Clabby M. Severe aortopathy due to fibulin-4 deficiency: molecular insights, surgical strategy, and a review of the literature. European journal of pediatrics. 2014. PMID: 24276535
- Almheiri S, Musa A. Beyond the genome: a rare case report of cutis laxa. AME case reports. 2026. PMID: 41676178