1q21.1 deletion syndrome

Overview

1q21.1 deletion syndrome is a rare chromosomal disorder caused by the loss of a small segment of genetic material on the long arm (q) of chromosome 1 at position 21.1. The condition is part of a group of genomic disorders known as copy number variations (CNVs) and is associated with a wide range of developmental, neurological, and physical features. The clinical presentation is highly variable - some individuals have significant health and developmental challenges, while others may have few or no symptoms.

Causes

1q21.1 deletion syndrome is caused by a deletion of approximately 1.35 to 2 megabases in the 1q21.1 region of chromosome 1. This deletion results in the loss of multiple genes believed to be involved in brain development, cardiac function, and cellular signaling.

The condition can occur in two ways:

• De novo (sporadic): The majority of cases occur randomly and are not inherited from either parent.

• Inherited: In some cases, the deletion is passed down from a parent who may have mild or no symptoms (incomplete penetrance).

Symptoms

There is significant variability in the symptoms and severity of 1q21.1 deletion syndrome. Commonly reported features include:

• Developmental delays: Especially in speech and motor skills

• Intellectual disability: Ranging from mild to moderate

• Autism spectrum disorder (ASD): Or autistic traits

• Behavioral and psychiatric issues: Including ADHD, anxiety, or schizophrenia in some cases

• Hypotonia (low muscle tone)

• Microcephaly (small head size) or macrocephaly (large head size), depending on individual variation

• Congenital heart defects: Including septal defects or valve abnormalities

• Dysmorphic facial features: Such as a broad forehead, deep-set eyes, or low-set ears

• Seizures: Reported in some individuals

Some people with this deletion may have no apparent clinical symptoms and remain undiagnosed.

Diagnosis

Diagnosis of 1q21.1 deletion syndrome is made through genetic testing. Common diagnostic steps include:

• Chromosomal microarray analysis (CMA): Detects the microdeletion and is the most common diagnostic tool

• Karyotyping: May detect larger deletions but can miss smaller ones

• Fluorescence in situ hybridization (FISH): Used in some settings to confirm the deletion

• Parental testing: Helps determine whether the deletion is inherited or de novo

Diagnosis is often initiated due to developmental delays, congenital anomalies, or behavioral concerns.

Treatment

There is no cure for 1q21.1 deletion syndrome, but early interventions and supportive therapies can significantly improve outcomes. Treatment is tailored to the individual's specific needs and may include:

• Speech, occupational, and physical therapy: For developmental and motor delays

• Special education services: Individualized education plans (IEPs) to address learning challenges

• Behavioral and psychological therapy: For autism, ADHD, or anxiety

• Cardiac care: For individuals with congenital heart defects

• Neurological care: If seizures or other neurological symptoms are present

• Genetic counseling: For families planning future pregnancies

Prognosis

The prognosis for individuals with 1q21.1 deletion syndrome is highly variable. Some people lead typical lives with minimal impact, while others may have significant developmental, medical, or psychiatric needs. Early diagnosis and consistent supportive care can help improve developmental outcomes and quality of life. Because the condition can be inherited, family members may also be tested to assess recurrence risk and better understand the genetic implications.