Koolen-de Vries syndrome

Koolen-de Vries syndrome is a multisystem neurodevelopmental condition characterized by distinctive facial features, low muscle tone, and a characteristically friendly disposition. It is caused by changes in the KANSL1 gene, which helps regulate the activity of many other genes during early growth and brain development. Signs and symptoms typically become apparent in infancy or early childhood and affect individuals of all sexes. Precise prevalence figures are not available, but published reports suggest the syndrome is uncommon, with only a limited number of affected individuals identified worldwide.

Early clues often include generalized hypotonia that makes feeding and motor milestones such as sitting or walking more difficult. Global developmental delay is universal, and most children benefit from extra support with speech, language, and other cognitive skills. Facial characteristics such as a broad forehead, pear-shaped or bulbous nose, upslanted eye openings, and a wide smile frequently help clinicians recognize the syndrome. Many families notice an unusually amiable or sociable behavior that is considered a hallmark of the condition. As children grow, additional neurological features can emerge, including seizures in a minority of individuals and ventriculomegaly visible on brain imaging. Orthopedic concerns such as joint hypermobility, scoliosis, hip dysplasia, and positional foot differences may require ongoing attention. Vision problems (strabismus or farsightedness), feeding difficulties in infancy, and distinct fingertip pads are also reported. Not all individuals experience all features, and severity varies considerably, even among people with the same genetic change.

Koolen-de Vries syndrome results from pathogenic variants or small chromosomal deletions involving the KANSL1 gene on chromosome 17q21.31. KANSL1 encodes a protein that is part of a chromatin-modifying complex, so its disruption alters the way many other genes are switched on or off during development, particularly in the nervous system. The condition follows an autosomal dominant inheritance pattern, meaning one altered copy of KANSL1 is sufficient to cause symptoms. When a parent carries the variant, each child has a 50 percent chance of inheriting it; however, some cases arise for the first time in the affected individual. Expressivity is variable, so the specific features and their severity can differ widely between people who share the same variant. Genetic counseling is strongly recommended for families to discuss testing options, recurrence risks, and family planning considerations.

Currently, management focuses on supportive care tailored to each individual’s needs. Early intervention services, physical therapy, occupational therapy, and speech therapy address developmental and cognitive challenges. Seizures, when present, are treated with standard anti-seizure medications prescribed by a neurologist. Orthopedic interventions may include bracing or surgery for scoliosis or hip dysplasia, while vision problems often require glasses or corrective procedures. Because the condition affects multiple body systems, care is best coordinated by a multidisciplinary team that may include neurology, cardiology, orthopedics, ophthalmology, and rehabilitation specialists. Regular surveillance is an essential part of long-term management, including monitoring of spine curvature, joint stability, growth, and developmental progress, so that emerging complications can be addressed promptly. Families are encouraged to maintain close communication with their healthcare providers to adjust therapies as needs change over time.

Most individuals with Koolen-de Vries syndrome make steady developmental gains with appropriate therapies, though many will continue to need educational and occupational support into adulthood. Medical complications such as seizures or orthopedic issues can generally be managed, and available reports suggest overall life expectancy is favorable, though long-term data remain limited. Severity and symptoms vary widely between individuals, making it difficult to predict a specific course for any one person. 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 to plan supportive services and address future care needs.

Clinical trials are underway exploring new approaches to support people with Koolen-de Vries syndrome and to better understand the role of KANSL1 in development. Individuals interested in research opportunities can search ClinicalTrials.gov or consult their care team about eligibility.