Kleefstra syndrome 1

Kleefstra Syndrome: A Rare Genetic Disorder

Kleefstra syndrome is a rare genetic disorder that affects multiple parts of the body, leading to various physical and developmental challenges.

• Developmental Delay and Intellectual Disability: Individuals with Kleefstra syndrome often experience significant delays in development and intellectual disability, which can impact their cognitive abilities and learning capacity [1].
• Weak Muscle Tone (Hypotonia): People with this condition may have weak muscle tone, particularly in childhood, which can affect their overall physical development and coordination [2].
• Severely Limited or Absent Speech: Kleefstra syndrome is often characterized by severely limited or absent speech, making communication a significant challenge for those affected [1].

These characteristic features of Kleefstra syndrome highlight the complexities of this rare genetic disorder.

Kleefstra syndrome is a rare genetic disorder characterized by intellectual disability, childhood hypotonia, severe expressive speech delay, and distinctive facial features.

Common symptoms include:

• Intellectual disability [2]
• Developmental delay [3]
• Severe expressive speech delay [4][5]
• Childhood hypotonia (low muscle tone) [7][8]

Additional symptoms may occur:

• Epilepsy (seizures) and/or febrile seizures (seizures in the setting of a fever) [1]
• Hearing loss [1]
• Autistic-like features [8]

Distinctive facial features:

• Flat face with widely spaced eyes [6]
• Arched eyebrows [6]
• Other facial features may vary, but these are commonly reported in individuals with Kleefstra syndrome.

It's essential to note that each individual with Kleefstra syndrome may experience a unique set of symptoms and characteristics. If you suspect someone has this condition, consult with a medical professional for an accurate diagnosis and guidance.

Kleefstra syndrome can be diagnosed through various diagnostic tests, which are essential for identifying the condition and ruling out other potential causes.

• Genetic testing: This is a crucial step in diagnosing Kleefstra syndrome. Genetic testing involves analyzing the DNA sequence of the EHMT1 gene to detect any mutations or deletions that may be causing the condition [1][2]. Chromosomal microarray, intellectual disability gene panels, whole exome, and whole genome sequencing are some of the genetic tests used for diagnosis [3][4].
• Magnetic Resonance Imaging (MRI): An MRI scan can help create detailed images of the brain and other parts of the body, which may show abnormalities associated with Kleefstra syndrome [2].
• Clinical history and examination: A thorough clinical evaluation by a healthcare professional is essential to identify the diagnostic features of the condition, such as developmental delays or intellectual disabilities, unusual physical features, seizures, or abnormal EEG results [5][9].

It's worth noting that commercial FISH probes can sometimes show normal results in children who have lost the EHMT1 gene, making correct diagnosis dependent on MLPA and/or EHMT1 sequencing [6][8].

Treatment Options for Kleefstra Syndrome

Kleefstra syndrome, a rare genetic disorder, requires a multidisciplinary team approach to treatment. While there is no cure for the condition, various therapies and interventions can help manage its symptoms.

• Pharmacological Treatment: Studies have shown that patients with Kleefstra syndrome may benefit from pharmacological treatment, including propranolol and clonidine, as well as haloperidol and risperidone to treat behavioral issues [2][6].
• Atypical Drugs: Atypical drugs, such as olanzapine and aripiprazole, have been observed to be effective in managing symptoms of Kleefstra syndrome with fewer side effects [11].
• Vagus Nerve Stimulation (VNS): VNS can be considered as an additional treatment option for patients experiencing seizures, which affects about 30% of those diagnosed with Kleefstra syndrome [14].

Clinical Trials and Research

Research into the development of orphan drugs specifically targeting Kleefstra syndrome is ongoing. The KIDS IQ Project is raising funds to support scientific research projects aimed at advancing a drug treatment for the condition [9]. Clinical trials are also being conducted to determine the effectiveness and safety of new treatments.

Important Considerations

• Individualized Approach: Each patient with Kleefstra syndrome should be evaluated on an individual basis, taking into account their unique needs and circumstances.
• Anesthetic Management: Patients with Kleefstra Syndrome may experience airway problems during anesthesia, requiring careful evaluation and management [12].
• Structural Brain Abnormalities: The presence of structural brain abnormalities should be documented in patients with Kleefstra syndrome.

References

[1] Knowledge on rare diseases and orphan drugs ... [2] by T Kleefstra · 2023 · Cited by 100 — Sleep disturbance as a precursor of severe regression in Kleefstra syndrome suggests a need for firm and rapid pharmacological treatment. [9] KIDS IQ Project is raising money for scientific research projects aimed at advancing a drug treatment for Kleefstra syndrome (KS). [11] Atypical drugs cause fewer side effects and are well tolerated by people with Kleefstra syndrome. A study of 24 people with Kleefstra syndrome observed the best effect was given by olanzapine and in some cases by aripiprazole. [12] Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. Observational studies involve recording changes over time among a specific group of people in their natural settings. Learn more about clinical trials from this U.S. Food & Drug Administration webpage. [14] Kleefstra syndrome: Considerations about treatment strategy in 2 patients with a causative Ehmt1 mutation and apathy - Volume 41 Issue S1.

Kleefstra syndrome has several differential diagnoses, which are conditions that can present with similar symptoms and characteristics. Some of the disorders to consider in the differential diagnosis of Kleefstra Syndrome include:

• Downs Syndrome: This genetic disorder is characterized by intellectual disability, delayed speech, and physical abnormalities such as a flat face and short neck [9].
• Smith-Magenis Syndrome: A rare genetic disorder that causes intellectual disability, delayed speech, and distinctive facial features, including a small jaw and large ears [9].
• Pitt-Hopkins Syndrome: A rare genetic disorder characterized by severe intellectual disability, delayed speech, and distinctive facial features, including a flat face and short neck [9].
• Angelman Syndrome: A genetic disorder that causes intellectual disability, delayed speech, and distinctive facial features, including a small jaw and large ears [2][9].
• Rett Syndrome: A rare genetic disorder that affects brain development, causing intellectual disability, delayed speech, and physical abnormalities such as loss of muscle tone [10].
• 2q23.1 microdeletion syndromes: A group of rare genetic disorders caused by a deletion of genetic material on the long arm of chromosome 2, which can lead to intellectual disability, developmental delay, and distinctive facial features [5].

It's worth noting that targeted genetic testing is possible for Kleefstra syndrome, which can help differentiate it from these other conditions.