Summary about Disease
Kleefstra syndrome (KS) is a rare genetic disorder characterized by intellectual disability, developmental delay, distinctive facial features, and hypotonia (low muscle tone). It is primarily caused by a deletion or mutation of the EHMT1 gene located on chromosome 9q34.3. The severity of symptoms can vary significantly among affected individuals.
Symptoms
Intellectual disability: Ranges from mild to severe.
Developmental delay: Affects speech, motor skills (sitting, walking), and social skills.
Hypotonia: Low muscle tone, leading to floppiness and feeding difficulties in infancy.
Distinctive facial features: These may include a flattened face, widely spaced eyes (hypertelorism), a prominent forehead, a short nose, a broad nasal bridge, and a protruding tongue. Facial features can become more pronounced with age.
Behavioral problems: Autism spectrum disorder (ASD) features, aggressive behavior, anxiety, and sleep disturbances are common.
Speech difficulties: Significant speech delay or absence of speech.
Cardiac defects: Congenital heart defects may occur.
Kidney abnormalities: Renal problems can sometimes be present.
Seizures: Some individuals experience seizures.
Skeletal abnormalities: Scoliosis (curvature of the spine) or other skeletal problems are possible.
Obesity: A tendency towards weight gain is often observed.
Causes
Kleefstra syndrome is caused by:
Deletion of 9q34.3 chromosome region: This region contains the EHMT1 gene. A deletion means that a portion of the chromosome is missing.
Mutation of the EHMT1 gene: A change in the DNA sequence of the *EHMT1* gene itself.
The EHMT1 gene encodes a protein called euchromatic histone-lysine N-methyltransferase 1, which is an enzyme that modifies histones. Histones are proteins that DNA wraps around to form chromatin, and histone modification plays a role in gene expression. Loss or dysfunction of the EHMT1 protein disrupts normal development. In most cases, the genetic change is *de novo*, meaning it is new in the affected individual and not inherited from their parents. However, it can sometimes be inherited from a parent who has a balanced translocation involving the 9q34.3 region.
Medicine Used
There is no specific medication to cure Kleefstra syndrome. Treatment focuses on managing individual symptoms and improving the quality of life:
Anti-seizure medications: For individuals with seizures.
Medications for behavioral problems: To manage aggression, anxiety, or other behavioral issues (e.g., antidepressants, antipsychotics, stimulants).
Cardiac medications: If there are heart defects, medications might be needed to manage heart failure or other complications.
Growth hormone therapy: In some cases where growth is significantly delayed, growth hormone may be considered.
Other medications: Depending on specific medical needs (e.g., medications for kidney problems).
Is Communicable
Kleefstra syndrome is not communicable. It is a genetic disorder and cannot be spread from person to person.
Precautions
There are no specific precautions to prevent Kleefstra syndrome as it is a genetic condition. Genetic counseling is recommended for families with a child affected by KS, especially if considering future pregnancies.
How long does an outbreak last?
Kleefstra Syndrome is not an outbreak. As a genetic disorder it does not have a defined beginning or end related to an outbreak scenario. It is a lifelong condition.
How is it diagnosed?
Kleefstra syndrome is diagnosed through:
Clinical evaluation: A doctor assesses the individual's physical characteristics, developmental milestones, and medical history.
Chromosomal microarray analysis (CMA): This test can detect deletions or duplications of chromosomal regions, including the 9q34.3 region.
Gene sequencing: Sequencing the EHMT1 gene can identify mutations within the gene.
FISH (Fluorescence In Situ Hybridization): A technique used to visualize specific DNA sequences on chromosomes. Can detect deletions in the 9q34.3 region.
Timeline of Symptoms
Infancy: Hypotonia, feeding difficulties, developmental delay.
Early childhood: Speech delay, distinctive facial features become more apparent, intellectual disability becomes more evident, behavioral problems may emerge.
Childhood and Adolescence: Continued developmental delay, potential for seizures, behavioral problems may persist or change, scoliosis may develop, obesity may become a concern.
Adulthood: Intellectual disability continues, behavioral problems may persist, monitoring for potential health complications (e.g., cardiac or kidney problems) is important. The specific timeline and severity of symptoms vary considerably among individuals.
Important Considerations
Early intervention: Early intervention programs (physical therapy, occupational therapy, speech therapy) are crucial to maximize a child's potential.
Special education: Individuals with KS often require special education services to support their learning and development.
Behavioral therapy: Behavioral therapy can help manage behavioral problems.
Multidisciplinary care: A team of specialists (pediatrician, geneticist, neurologist, cardiologist, nephrologist, psychiatrist, therapists) is important for comprehensive care.
Family support: Support groups and resources for families affected by KS are valuable.
Ongoing monitoring: Regular medical check-ups are necessary to monitor for potential health complications.
Genetic Counseling: Genetic counseling is essential for parents and other family members.