cutis laxa, autosomal dominant 3

Cutis laxa, autosomal dominant 3 is a connective tissue disorder primarily affecting the skin and multiple organ systems. It is characterized by thin, lax skin with visible veins and premature wrinkling, along with ocular changes such as cataract or corneal clouding, and distinct facial features including a broad forehead and triangular face. The condition is caused by heterozygous mutations in the ALDH18A1 gene and is inherited in an autosomal dominant manner. Precise prevalence estimates are not well established, and clinical findings along with molecular genetic testing are key in establishing the diagnosis.

Individuals with cutis laxa, autosomal dominant 3 typically present with skin findings such as markedly thin, lax skin, dermal translucency, and premature skin wrinkling, which are consistently observed. Characteristic facial features include a broad, prominent forehead, low-set and protruding ears, and a triangular face. In addition, almost all affected individuals show hypotonia, global developmental delay, and moderate intellectual disability, highlighting the central nervous system involvement. Other common features include joint hypermobility, clenched fingers, growth retardation (both pre- and postnatal), and, in some cases, feeding difficulties or microcephaly. Not all individuals experience all features, and severity varies considerably.

Cutis laxa, autosomal dominant 3 is caused by heterozygous mutations in the ALDH18A1 gene, which plays a role in amino acid metabolism and contributes to the structural integrity of connective tissues. The condition is inherited in an autosomal dominant pattern, meaning that a single copy of the altered gene can lead to the disorder. That even within the same family, the severity and specific symptoms can vary considerably (variable expressivity). Families are encouraged to pursue genetic counseling to better understand the implications for current and future family members.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved or foundational therapies specifically for cutis laxa, autosomal dominant 3. Treatment is tailored to the individual and typically involves a multidisciplinary team approach, with regular surveillance to monitor and manage complications related to growth, skin integrity, and neurodevelopment. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to help guide family planning and provide ongoing support.

The clinical course of cutis laxa, autosomal dominant 3 is variable, with outcomes depending on the severity of skin involvement, growth delays, and neurodevelopmental challenges. Although many individuals face ongoing challenges related to skin elasticity, musculoskeletal features, and intellectual impairment, modern multidisciplinary care continues to improve overall quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and appropriate specialists to navigate care options and plan for the future.