1p36 deletion syndrome

Overview

1p36 deletion syndrome is a rare chromosomal disorder caused by the deletion of genetic material from the short arm (p) of chromosome 1 at position 36. It is the most common terminal deletion syndrome, occurring in approximately 1 in 5,000 to 10,000 births. The condition affects multiple systems and results in a wide range of developmental, neurological, and physical abnormalities. The severity varies depending on the size and location of the deleted segment, but common features include intellectual disability, delayed speech, hypotonia, seizures, and distinctive facial characteristics.

Causes

1p36 deletion syndrome is caused by a missing segment of genetic material on the short arm of chromosome 1 (specifically at region 1p36). This deletion can occur:

• De novo (sporadically): Most cases occur as new genetic events, with no family history.

• Inherited: In rare cases, the deletion is inherited from a parent with a balanced chromosomal rearrangement (such as a translocation).

The deletion results in the loss of multiple genes that are important for brain development, heart function, and physical growth, which accounts for the multisystem involvement seen in affected individuals.

Symptoms

The clinical features of 1p36 deletion syndrome vary widely but may include:

• Intellectual disability: Ranging from mild to severe

• Developmental delays: Especially in motor skills and speech

• Hypotonia (low muscle tone): Noted from infancy

• Seizures: Often difficult to control and may begin in infancy or early childhood

• Distinctive facial features: Including deep-set eyes, flat nasal bridge, pointed chin, and straight eyebrows

• Hearing and vision problems

• Congenital heart defects: Such as atrial or ventricular septal defects

• Feeding difficulties: Especially in infancy, sometimes requiring feeding support

• Behavioral issues: Including hyperactivity or self-injury in some cases

Diagnosis

Diagnosis is typically made through genetic testing. Steps include:

• Clinical evaluation: Based on developmental delays, physical features, or medical history

• Chromosomal microarray analysis (CMA): Detects submicroscopic deletions including 1p36

• Karyotyping: May reveal larger chromosomal deletions or rearrangements

• Fluorescence in situ hybridization (FISH): Used in some cases to confirm deletions at 1p36

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

Treatment

There is no cure for 1p36 deletion syndrome, but early and ongoing intervention can improve outcomes. Management is multidisciplinary and tailored to individual needs:

• Early intervention programs: Including physical, occupational, and speech therapy

• Seizure management: Antiepileptic medications and neurological follow-up

• Cardiology care: For congenital heart defects

• Feeding support: May include feeding therapy or gastrostomy tube placement

• Educational support: Individualized Education Programs (IEPs) and special education services

• Behavioral therapy: To address emotional or social difficulties

• Regular hearing and vision screening

Prognosis

The long-term outlook for individuals with 1p36 deletion syndrome varies. While many will have lifelong intellectual and physical disabilities, early and consistent support can greatly enhance their developmental potential and quality of life. Life expectancy may be reduced in those with severe heart defects or uncontrolled seizures, but many individuals live into adulthood with appropriate medical and developmental care.