Witteveen-Kolk syndrome, often referred to as WITKOS, is a rare neurodevelopmental disorder that affects individuals from early development. It is characterized by a range of physical and developmental features that can vary among those diagnosed. The syndrome was identified by developmental neuroscientists Josefine S. Witteveen and Sharon M. Kolk in 2016.
Approximately 40 to 50 individuals have been reported globally. Both males and females are affected equally, and understanding the condition’s complexities is important for individuals, families, and healthcare providers.
Understanding Witteveen-Kolk Syndrome
Witteveen-Kolk syndrome is a genetic neurodevelopmental syndrome that impacts the development of the brain and nervous system. This can lead to various developmental delays and intellectual differences. The syndrome is also known as SIN3A-related intellectual disability syndrome or 15q24 microdeletion syndrome.
The condition can affect multiple body systems, leading to a broad spectrum of signs. These include challenges with growth and feeding, as well as distinct facial features. The presentation of the syndrome can differ significantly from person to person.
The Genetic Basis
Witteveen-Kolk syndrome arises from changes in the SIN3A gene, which can be specific mutations or microdeletions involving the loss of genetic material. The SIN3A gene is located on chromosome 15, specifically in the 15q24.2 region.
The SIN3A gene provides instructions for making the SIN3A protein, which controls the activity of other genes. An alteration in one copy of the SIN3A gene leads to haploinsufficiency, meaning there is not enough functional SIN3A protein. This altered gene function disrupts various developmental processes, particularly those involved in brain development. The inheritance pattern for Witteveen-Kolk syndrome is autosomal dominant, meaning only one altered copy of the gene is needed for the condition to manifest.
Recognizing the Characteristics
Developmental delays are common in individuals with Witteveen-Kolk syndrome, affecting areas such as motor skills and speech. Intellectual disability is also a frequent feature, often presenting as mild, though about 25% of individuals may not have cognitive impairment.
Distinctive facial features are often observed, including a tall, broad forehead, down-slanting eyelids, a triangular face with a pointed chin, and a thin upper lip. Other physical traits can include short stature, small head size, weak muscle tone (hypotonia), and loose joints. Feeding difficulties are reported in about half of affected individuals, and some may experience seizures. Behavioral and psychiatric conditions, such as attention deficit hyperactivity disorder, autism spectrum disorder, anxiety, and aggressive behavior, are also reported in about a third of individuals.
Diagnosis and Management
Diagnosing Witteveen-Kolk syndrome involves genetic testing. Methods such as chromosomal microarray analysis, intellectual disability gene panels, whole exome sequencing, or whole genome sequencing are used to identify mutations or microdeletions in the SIN3A gene. A clinical genetic specialist usually conducts this evaluation.
Management involves a multidisciplinary approach. This team may include a pediatrician, clinical geneticist, and psychiatrist, with referrals to neurologists or ophthalmologists as needed. Therapies such as physical, occupational, and speech therapy are often recommended to support developmental progress. Educational support and early intervention for behavioral conditions are also provided.
Family Planning and Support
For families affected by Witteveen-Kolk syndrome, genetic counseling is available. Genetic counselors provide information about the syndrome’s inheritance pattern and assess the risk of recurrence for future pregnancies. While many cases are sporadic, resulting from new gene mutations, there is a 50% recurrence risk if one parent is affected due to the autosomal dominant inheritance.
Support networks, patient advocacy groups, and community resources assist families. Organizations such as Unique, COMBINEDBrain Inc., and Global Genes offer information, support, and connections to other families and resources. These groups provide a sense of community and help families navigate the challenges associated with rare genetic conditions.