9q34 deletion syndrome

Medical Condition
[[File:|250px|alt=|]]
Synonyms	Kleefstra syndrome
Pronounce	N/A
Field	N/A
Symptoms	N/A
Complications
Onset
Duration
Types
Causes
Risks
Diagnosis
Differential diagnosis
Prevention
Treatment
Medication
Prognosis
Frequency
Deaths

9q34 deletion syndrome, also known as Kleefstra syndrome, is a rare genetic disorder caused by deletions in the chromosome 9q34 region. This condition is associated with a variety of physical, developmental, and behavioral symptoms, including childhood hypotonia, a distinct facial appearance, and developmental disabilities. Common facial features include arched eyebrows, a small head circumference, midface hypoplasia, a prominent jaw, and a pouting lower lip. Individuals with Kleefstra syndrome often experience speech delays and difficulties, as well as epilepsy, congenital and urogenital defects, microcephaly, obesity, and psychiatric conditions.

The condition results from mutations in the EHMT1 gene, which encodes a histone methyltransferase involved in regulating gene activity. A frameshift mutation, missense mutation, or nonsense mutation in the coding sequence of EHMT1 can disrupt its function, leading to the development of the syndrome.

Signs and Symptoms

Physical Symptoms

• Heart defects
• Autism spectrum disorder traits
• Genital defects (more common in males)
• Childhood hypotonia (low muscle tone)
• Respiratory infections
• Delayed motor skills
• Renal defects

Behavioral Symptoms

• Passive behavior
• Sociability challenges
• Aggression (e.g., biting or hitting)
• Moodiness
• Sensitivity to routine changes

Genetics

Kleefstra syndrome primarily results from de novo mutations, although some cases may arise from inherited chromosomal translocations. In a rare case, a mother carrying a mosaicism for the EHMT1 mutation passed the condition to her child. The mosaicism in the mother led to incomplete gene splicing, contributing to the pathogenesis of the disease.

Historically, the severity of the disease was thought to correlate with the extent of EHMT1 deletions. However, newer research indicates that even when EHMT1 is non-functional without deletions, the syndrome can still occur, demonstrating the importance of EHMT1 gene disruption.

Diagnosis

The diagnosis of Kleefstra syndrome is typically made through genetic testing, which may include:

• Fluorescence in situ hybridization (FISH)
• Multiplex ligation-dependent probe amplification (MLPA)
• Array comparative genomic hybridization (aCGH)
• EHMT1 sequencing

FISH uses colored probes to detect chromosomal irregularities, while MLPA identifies DNA copy number changes. aCGH helps detect deletions or amplifications of genetic material, and EHMT1 sequencing maps the gene's coding sequence to identify mutations.

Treatment

Treatment for Kleefstra syndrome is multidisciplinary, focusing on managing individual symptoms. This often involves a team of specialists, including neurologists, geneticists, pediatricians, and psychologists, who collaborate to address the physical, developmental, and behavioral challenges presented by the condition.

Epidemiology

Kleefstra syndrome affects both males and females equally. Approximately 75% of cases are linked to disruptions in the EHMT1 gene, while the remaining 25% are caused by deletions of the 9q34 region. Due to the rarity of the condition, there is limited data on its impact on life expectancy.

History

Kleefstra syndrome is a relatively new discovery, and fewer than 200 cases have been reported. The precise origin of the condition remains unclear, as it is a rare genetic disorder with limited historical documentation.

Research

Recent studies have deepened our understanding of Kleefstra syndrome. One study analyzed the EHMT1 gene in 23 patients, most of whom were children, and found several new mutations. This research emphasized the role of EHMT1 in the pathogenesis of the disease, showing that disruptions in this gene lead to the hallmark symptoms of the syndrome.

A further study published in the Journal of Medical Genetics involved 40 patients who underwent genetic testing, revealing new mutations in the EHMT1 gene, further confirming its central role in the disorder. These findings contributed to the growing body of evidence supporting the connection between EHMT1 mutations and the clinical manifestations of Kleefstra syndrome.

External links

Classification	ICD-10: Q93.5 OMIM: 610253 DiseasesDB: 32302
External resources

• Genetics Home Reference website on Kleefstra Syndrome