de Sanctis-Cacchione syndrome

De Sanctis-Cacchione syndrome is a rare multisystem condition that primarily affects the skin and nervous system. It is characterized by features of xeroderma pigmentosum along with significant neurological abnormalities such as intellectual disability and mental deterioration. Mutations in the ERCC6 gene underlie this autosomal recessive disorder, meaning that two copies of the altered gene are required for the syndrome to manifest. Precise prevalence estimates are not well established, and affected individuals often present in early childhood with a constellation of symptoms that evolve over time.

Individuals with de Sanctis-Cacchione syndrome typically present with distinctive dermatologic and neurologic abnormalities. The skin findings include cutaneous photosensitivity, hypermelanotic macules, and telangiectasia, while neurologically, affected individuals may exhibit global developmental delay, intellectual disability, and mental deterioration. Additional characteristic features include microcephaly, hyporeflexia, olivopontocerebellar atrophy, leukodystrophy, and a positive Babinski sign. Musculoskeletal manifestations such as equinovarus deformity and severe short stature, as well as endocrine features like bilateral cryptorchidism, also contribute to the clinical picture. Not all individuals experience all of these features, and severity varies considerably.

The underlying cause of de Sanctis-Cacchione syndrome is linked to pathogenic variants in the ERCC6 gene. This gene plays a critical role in DNA repair, and when it is disrupted, it leads to the cumulative damage observed in the skin and nervous system. The condition is inherited in an autosomal recessive manner, meaning that an affected individual has inherited one mutated copy of the gene from each parent. As a result, genetic counseling is recommended for families to understand recurrence risks and discuss family planning options.

Currently, management for de Sanctis-Cacchione syndrome focuses on supportive care and symptom management, with treatment tailored to the individual’s specific needs. A multidisciplinary approach is essential, involving specialists experienced in managing dermatologic, neurological, orthopedic, and endocrine issues. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. In addition, genetic counseling is recommended to help families understand the inherited nature of the condition and navigate complex treatment decisions. Patients should discuss treatment options with their healthcare team to determine the best supportive strategies for their situation.

The long-term outlook for individuals with de Sanctis-Cacchione syndrome is highly variable, with outcomes that depend on the severity of symptoms and the timeliness of supportive interventions. Although the condition includes progressive features such as mental deterioration and neurologic abnormalities, many individuals benefit from advances in care that help maintain quality of life. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists experienced in managing the condition. Genetic counseling remains an important next step for families as they navigate ongoing care.