Cutis laxa type 1A

Overview

Cutis laxa type 1A is a rare inherited disorder primarily affecting connective tissue, the material that provides support to the skin and other organs. The most noticeable feature is skin that appears loose, wrinkled, and lacking elasticity, often giving an aged appearance [PMID:31548079]. This condition is present from birth (congenital) and can vary in how severely it affects individuals. Beyond the skin, other body systems, including the heart, lungs, and blood vessels, can also be affected, leading to a range of potential health challenges.

Symptoms & clinical features

Individuals with cutis laxa type 1A typically have skin that hangs in folds, particularly around the face, neck, and joints, and does not return to its original position quickly when stretched. This can make the skin appear aged and lax. Other common skin features include decreased skin elasticity and fragility. Beyond the skin, the condition can also impact internal organs [PMID:31548079]. Pulmonary emphysema, a lung condition, is a frequent complication. Cardiovascular issues may include conditions like aortic aneurysm, which is a bulging of the large artery leading from the heart, and other blood vessel abnormalities. Gastrointestinal problems, such as diverticula (small pouches in the digestive tract), can also occur.

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Affected organs

The primary organs affected in cutis laxa type 1A are the skin, lungs, and cardiovascular system. The skin lacks elasticity due to problems with the connective tissue. The lungs can develop emphysema, which impairs breathing. The heart and blood vessels may be affected by weakened connective tissue, potentially leading to aneurysms or other structural issues. Occasionally, the bladder and gastrointestinal tract can also be involved, leading to diverticula or other functional issues. The skeletal system may show subtle signs, such as joint laxity, though this is less prominent than the skin and internal organ involvement.

Multiple body systems

Systemic involvement

Cellular impact

Mechanism at cellular level

Risks & severity

Cutis laxa type 1A can present with a wide range of severity, even within the same family. While the primary skin manifestations are typically noticeable from birth, the internal organ involvement can progress over time. For example, lung problems like emphysema and cardiovascular issues such as aortic aneurysms can develop or worsen, potentially leading to severe health complications [PMID:24653606]. The exact prevalence of cutis laxa type 1A is not well established, but it is considered a very rare condition. Life expectancy can be reduced in more severe cases, particularly if there is significant cardiac or pulmonary involvement, making careful medical management important.

Genetic causes

Cutis laxa type 1A is caused by pathogenic variants in the FBLN5 gene [PMID:24653606]. The FBLN5 gene provides instructions for making a protein called fibulin 5. This protein is crucial for the formation of elastic fibres, which are a major component of connective tissue and give skin and blood vessels their elasticity and strength. Pathogenic variants in FBLN5 disrupt the normal production or function of fibulin 5. This impairment means that elastic fibres cannot form correctly, leading to the characteristic loose, inelastic skin and the potential for weakened connective tissue in other parts of the body.

• FBLN5
  fibulin 5

Inheritance pattern

Cutis laxa type 1A is inherited in an autosomal recessive pattern. This means that an individual must inherit two copies of the changed FBLN5 gene - one from each parent - to develop the condition. People who have only one copy of the changed gene are called carriers. Carriers typically do not show symptoms of cutis laxa type 1A, but they can pass the changed gene on to their children. If two carriers have children together, there is a 1 in 4 (25%) chance with each pregnancy that their child will inherit two changed copies of the gene and develop cutis laxa type 1A.

Diagnosis & testing

Diagnosis of cutis laxa type 1A typically begins with a clinical assessment based on the visible skin features and any associated health concerns affecting internal organs. A definitive diagnosis is confirmed through genetic testing, which can identify pathogenic variants in the FBLN5 gene. In the UK, genetic testing for suspected inherited conditions often follows a referral from a specialist clinician (e.g., a paediatrician or dermatologist) to a clinical genetics service. This service can arrange appropriate genomic testing, which may be covered by an NHS R-code, such as R323 Congenital Cutis Laxa. Genetic counselling is usually offered alongside testing to explain the implications of the results for the individual and their family.

Management & lifestyle

Due to the variable nature of cutis laxa type 1A, management focuses on addressing the specific symptoms and potential complications an individual may experience. There is no cure for the underlying genetic cause. Regular monitoring for internal organ involvement, especially regarding the cardiovascular and respiratory systems, is often recommended. This may include regular cardiac assessments and lung function tests. Surgical interventions may be considered for severe skin laxity, although results can be temporary, and for certain internal complications like large aneurysms. Lifestyle adjustments, such as avoiding activities that might put excessive strain on weakened tissues, may be advised. Management in the UK generally involves a multidisciplinary team approach, coordinated through specialist clinics, to provide comprehensive and ongoing care.

UK care pathway

In the UK, individuals suspected of having a rare genetic condition like cutis laxa type 1A are typically referred by their GP or another specialist to an NHS Clinical Genetics service. Here, a clinical geneticist and genetic counsellor can assess the individual and family history, discuss appropriate genomic testing (which may fall under an NHS R-code like R323 for congenital cutis laxa), and explain inheritance patterns and potential health implications. Genetic counsellors provide support and information, helping families make informed decisions about testing and management. The results of genomic tests guide further specialist referrals and ongoing care within the NHS.

Related conditions

Several conditions can cause skin laxity, and differentiating cutis laxa type 1A from others is important. Other forms of cutis laxa, caused by changes in different genes, can have similar skin features but may differ in their associated organ involvement and inheritance patterns. Elastic tissue disorders, such as Ehlers-Danlos syndromes, can also present with skin hyperextensibility and fragility, but typically have distinct genetic causes and clinical profiles. Marfan syndrome and pseudoxanthoma elasticum are other connective tissue disorders that may need to be considered when evaluating a patient with loose or fragile skin.

Frequently asked questions