deafness-encephaloneuropathy-obesity-valvulopathy syndrome

Deafness-encephaloneuropathy-obesity-valvulopathy syndrome is a rare mitochondrial disorder that affects multiple organ systems, including the nervous system, heart, auditory system, and kidneys. The condition is caused by mutations in the PDSS1 gene, which plays a critical role in coenzyme Q10 biosynthesis and proper mitochondrial function. It typically presents in childhood with features such as early-onset deafness and cardiac abnormalities, although there is marked variability in clinical presentation. Given its very rare prevalence, affecting fewer than 1 in 1,000,000 people, families are encouraged to seek genetic counseling and connect with specialists familiar with this condition.

The clinical features of this syndrome are diverse, reflecting its multisystem impact. Neurologically, affected individuals often exhibit encephalomyopathy and mild intellectual disability while some may experience seizures. The auditory system is prominently involved, with early-onset deafness seen in all cases, and peripheral neuropathy is also consistently observed. Cardiac manifestations, including mitral and aortic regurgitation, are a defining aspect, and additional features such as optic atrophy, macrocephaly, obesity, increased circulating lactate with an elevated lactate:pyruvate ratio, and livedo reticularis complete the clinical picture. Not all individuals experience every feature and severity varies considerably.

This condition is caused by pathogenic variants in the PDSS1 gene. PDSS1 is essential for the biosynthesis of coenzyme Q10 within mitochondria, and disruption in its function leads to impaired energy production, which contributes to the wide range of clinical features seen in affected individuals. Deafness-encephaloneuropathy-obesity-valvulopathy syndrome is inherited in an autosomal recessive pattern, meaning that two mutated copies of the gene, one inherited from each parent, are required for an individual to be affected. This condition is more commonly observed when parents share a common ancestor, which increases the likelihood that both carry the same rare genetic change, and each pregnancy carries a 25% recurrence risk.

Currently, management focuses on supportive care and symptom management rather than any specific curative therapy. Treatment is tailored to the individual and typically involves a multidisciplinary team that may include neurologists, cardiologists, audiologists, and metabolic specialists. In addition to addressing acute symptoms, regular surveillance is an essential part of long-term care, helping to identify potential complications early. Patients are encouraged to discuss treatment options with their healthcare team and to consider genetic counseling to understand implications for family planning and long-term management.

The course of deafness-encephaloneuropathy-obesity-valvulopathy syndrome is highly variable, with outcomes depending on the severity of symptoms, age at diagnosis, and access to appropriate care. With current standards of care, many individuals benefit from ongoing surveillance and supportive management, which can help maintain quality of life. Outcomes described in medical literature continue to evolve as standards of care improve, and families are advised to connect with specialists for tailored management strategies. That severity and symptoms vary widely between affected individuals, and genetic counseling can provide further guidance regarding family planning and long-term expectations.

Clinical trials are underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.