Kleefstra syndrome (KS) is a rare genetic condition that affects many body systems and influences development. It is characterized by intellectual disability, alongside a range of other physical and clinical features. The syndrome impacts individuals differently, with varied symptoms and severity levels. Understanding this condition involves exploring its genetic underpinnings, common characteristics, diagnosis, and ongoing care.
Genetic Origin
Kleefstra syndrome is caused by changes in the EHMT1 gene (euchromatic histone-lysine N-methyltransferase 1), located on chromosome 9 (9q34.3 region). The condition arises from either a deletion of chromosome 9 containing EHMT1, or a mutation within the gene itself.
The EHMT1 gene provides instructions for creating euchromatic histone methyltransferase 1, an enzyme modifying histones. This enzyme helps suppress gene activity by adding methyl groups to histones, which are structural components DNA wraps around. When one copy of the EHMT1 gene is non-functional, it leads to insufficient protein levels, affecting the regulation of many genes involved in development.
Most Kleefstra syndrome cases occur spontaneously (de novo). In rare instances, the condition can be inherited if a parent carries a balanced chromosomal rearrangement or mosaicism for the deletion. Severity varies; larger deletions in the 9q34.3 region can lead to more pronounced intellectual disability and additional health issues, though a direct correlation with symptom severity is not always observed.
Common Characteristics
Individuals with Kleefstra syndrome experience developmental delays and intellectual disability, ranging from moderate to severe. Speech development is significantly delayed, often resulting in limited or no verbal communication, though non-verbal communication may be more advanced. Low muscle tone (hypotonia) is common in childhood, contributing to delays in motor skills.
The syndrome is associated with distinctive facial features that vary and may become more noticeable with age. These include a prominent forehead, arched or joined eyebrows, widely spaced eyes, a flattened midface, and a full, everted lower lip. Other physical traits are a small head size, a wide and short skull, a protruding tongue, and a prominent jaw.
Beyond developmental and physical traits, individuals with Kleefstra syndrome encounter medical and behavioral challenges. Common neurological issues include seizures and sleep disturbances. Behavioral characteristics include autistic-like behaviors, repetitive movements, and sometimes aggression or self-injury, though individuals often exhibit a friendly disposition. Health concerns include congenital heart defects, kidney abnormalities, recurrent respiratory infections, feeding difficulties, hearing loss, and vision problems.
Diagnosis and Ongoing Care
Diagnosis of Kleefstra syndrome begins when clinical features suggest the condition. Professionals identify characteristic physical appearance, developmental delays, and intellectual disability. Definitive diagnosis relies on genetic testing, identifying specific changes in the EHMT1 gene or the 9q34.3 region of chromosome 9.
Common genetic tests include chromosomal microarray analysis (CMA) or gene sequencing of EHMT1. CMA detects microdeletions of chromosome 9q34.3, while gene sequencing identifies smaller mutations within the EHMT1 gene. Early diagnosis allows for prompt initiation of appropriate support and interventions.
Ongoing care for individuals with Kleefstra syndrome requires a comprehensive, multidisciplinary approach. A team of specialists includes neurologists, cardiologists, nephrologists, and developmental pediatricians. Therapeutic interventions support development, with physical therapy addressing motor skills, occupational therapy focusing on daily living activities, and speech-language therapy aiding communication.
Behavioral therapy and educational support are tailored to individual needs, helping manage specific challenges and foster learning. Routine medical monitoring detects and manages potential health issues affecting the heart, kidneys, vision, and hearing. This integrated approach supports the individual’s overall well-being and development.
Life with Kleefstra Syndrome
Living with Kleefstra syndrome involves a lifelong journey, both for affected individuals and their families. The condition presents ongoing challenges related to development and health, requiring continuous adaptation and support. Individuals with Kleefstra syndrome can achieve fulfilling lives when provided with appropriate resources and personalized care plans.
Support networks, including family, friends, and professional caregivers, enhance the quality of life for those with the syndrome. Connecting with community groups and advocacy organizations offers valuable information, emotional support, and shared experiences for families. These groups raise awareness and support ongoing research efforts.
Research into Kleefstra syndrome continues to advance, aiming to deepen understanding of its genetic mechanisms and explore interventions. Efforts focus on identifying the EHMT1 gene’s precise role and developing new therapies, including pharmacological and behavioral approaches. The goal is to improve outcomes and maximize the potential of individuals living with Kleefstra syndrome.