autosomal recessive cutis laxa type 2B

Autosomal recessive cutis laxa type 2B is a very rare inherited disorder that primarily affects the skin, connective tissue, and overall growth and development. It is caused by pathogenic variants in the PYCR1 gene, which provides instructions for an enzyme involved in protein and collagen stability; disruption of this enzyme weakens connective tissue throughout the body. Symptoms usually begin before birth or in early infancy and affect both males and females. Fewer than one in a million people are thought to have the condition worldwide, so most clinicians will never encounter a case in routine practice. Because multiple body systems can be involved, affected individuals typically require coordinated care from several specialists.

The hallmark feature is cutis laxa—loose, thin skin that hangs in folds and has reduced elasticity. Parents often notice excessive wrinkling on the hands, feet, and face soon after birth. Many babies are small for their gestational age because of in-utero growth restriction and may experience failure to thrive in infancy. Characteristic facial findings include a broad or prominent forehead, narrow nose with a thin nasal ridge, sagging cheeks that give a prematurely aged appearance, and protruding ears. Connective-tissue fragility extends beyond the skin. Joint hypermobility, congenital hip dislocation, pes planus, and clubfoot (talipes equinovarus) can make early motor milestones difficult. Bones may be osteopenic, predisposing to fractures, and wormian bones can be seen on skull X-rays. Easy bruising and prominent superficial veins reflect fragile blood-vessel walls. Neurological and developmental features are common. Most children show global developmental delay with hypotonia, and many have intellectual disability. Severity and symptoms vary widely between individuals—not all experience every feature, and some achieve near-typical motor skills with therapy. Occasional cataracts or corneal clouding illustrate that the eyes can also be involved. Because the condition touches multiple systems, families may first seek medical attention for very different reasons—a newborn evaluation for wrinkled skin, an orthopedic consultation for hip instability, or a developmental assessment for delayed milestones. Recognizing the pattern of connective-tissue laxity, distinctive facial appearance, and developmental concerns is key to prompting genetic testing.

Autosomal recessive cutis laxa type 2B results from inheriting two non-working copies of the PYCR1 gene—one from each parent. PYCR1 encodes an enzyme that helps recycle the amino acid proline, a building block critical for collagen strength. When the enzyme is deficient, collagen fibers form abnormally, leading to loose skin and fragile connective tissue in many organs, including the brain. The condition follows an autosomal recessive inheritance pattern: if both parents are carriers, each pregnancy has a 25 percent chance of producing an affected child, a 50 percent chance of a carrier child, and a 25 percent chance of an unaffected non-carrier. This condition is more common when parents share a common ancestor, because relatives are more likely to carry the same rare genetic change. Carrier testing and genetic counseling are strongly recommended for family members who may be planning future pregnancies.

Currently, management focuses on supportive care and symptom management tailored to each individual. Physical and occupational therapy help improve strength, motor skills, and joint stability, while orthopedic interventions may be needed for hip dislocation or foot deformities. Regular dermatologic care keeps the fragile skin healthy and addresses cosmetic concerns. Because connective-tissue weakness can involve many organs, long-term care is multidisciplinary: specialists in genetics, orthopedics, neurology, ophthalmology, and dermatology often collaborate to create an integrated plan. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious; periodic eye exams, skeletal monitoring, and developmental assessments are commonly recommended. Families should discuss specific monitoring schedules with their healthcare team, and genetic counseling can clarify recurrence risks and family-planning options.

Outcomes depend on the combination and severity of features in each person. Some children make steady developmental gains with early therapies, while others continue to need significant medical and educational support. Skin laxity and skeletal issues are lifelong, but many complications can be managed effectively when identified early. Respiratory or cardiovascular problems are uncommon but can occur if connective-tissue weakness involves those systems, underscoring the need for ongoing monitoring. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and genetic counselors who can guide surveillance plans and provide up-to-date information about emerging research.