17q21.31 microdeletion syndrome

Overview

17q21.31 microdeletion syndrome is a rare genetic disorder caused by the deletion of a small segment of DNA on the long arm (q) of chromosome 17 at position 21.31. This syndrome affects multiple systems and is associated with global developmental delay, mild to moderate intellectual disability, distinctive facial features, and hypotonia. It was first described in the mid-2000s and is also referred to as Koolen–de Vries syndrome, named after the researchers who identified it. The condition is typically diagnosed in infancy or early childhood due to developmental concerns.

Causes

The syndrome is caused by a microdeletion in the 17q21.31 region of chromosome 17, which spans approximately 500–650 kilobases. This region includes several important genes, particularly KANSL1, which is believed to play the major role in causing the clinical features of the syndrome.

The microdeletion occurs as a de novo (spontaneous) event in almost all cases, meaning it is not inherited from either parent. However, individuals with the deletion can pass it on to their children, so it may be inherited in future generations.

Symptoms

Symptoms of 17q21.31 microdeletion syndrome can vary but typically include:

• Global developmental delay: Notably in motor and speech skills

• Intellectual disability: Usually mild to moderate

• Hypotonia (low muscle tone): Especially in infancy

• Friendly and outgoing personality

• Epilepsy or seizures: In some individuals

• Facial features: Including long face, high forehead, tubular or pear-shaped nose, and everted lower lip

• Joint laxity and hypermobility

• Feeding difficulties: Often requiring early feeding support

• Sleep disturbances

• Heart or kidney anomalies: Less common but possible

While developmental challenges are common, many individuals are described as cheerful and highly sociable.

Diagnosis

Diagnosis is confirmed through genetic testing. The process typically includes:

• Chromosomal microarray analysis (CMA): Detects the 17q21.31 microdeletion

• MLPA (Multiplex Ligation-dependent Probe Amplification): Sometimes used to confirm the deletion

• Parental testing: To determine if the deletion is inherited or de novo

Testing is often initiated in children with global developmental delays, distinctive features, or unexplained hypotonia.

Treatment

There is no cure for 17q21.31 microdeletion syndrome. Treatment is supportive and multidisciplinary, tailored to the child’s symptoms and needs:

• Early intervention: Physical, occupational, and speech therapy to support development

• Educational support: Special education services and individualized learning plans (IEPs)

• Seizure management: If epilepsy is present

• Feeding therapy: May include consultation with nutritionists or gastroenterologists

• Orthopedic and physical therapy: For joint laxity or motor coordination issues

• Behavioral and psychological support: As needed for emotional development

Prognosis

The prognosis for individuals with 17q21.31 microdeletion syndrome varies but is generally positive with appropriate interventions. Most children improve significantly with early therapy, and many go on to attend school with support. Intellectual disability is usually in the mild to moderate range. Life expectancy is not thought to be significantly reduced unless severe medical complications are present. Ongoing developmental and medical monitoring can help individuals achieve their full potential.