Contiguous gene syndrome

Overview

Contiguous Gene Syndrome (CGS) refers to a group of rare genetic disorders caused by the deletion or duplication of several neighboring (contiguous) genes located on the same chromosome segment. Because multiple genes are affected at once, individuals with CGS often present with a wide spectrum of clinical features that combine symptoms of several individual genetic conditions. These syndromes typically arise due to chromosomal microdeletions or microduplications and are often diagnosed through advanced genetic testing. Common examples include Williams syndrome, Smith-Magenis syndrome, and DiGeorge syndrome.

Causes

Contiguous Gene Syndromes are primarily caused by structural abnormalities in chromosomes, such as:

• Microdeletions: Loss of a small chromosomal region containing multiple genes

• Microduplications: Extra copies of a chromosomal region containing multiple genes

These chromosomal changes usually occur during gamete formation or early embryonic development and are typically de novo (not inherited), although they can occasionally be passed down in families. The phenotypic expression depends on which specific genes are involved and how they interact.

Symptoms

The symptoms of Contiguous Gene Syndromes vary widely depending on the specific region and genes involved. However, common features across many CGS types include:

• Developmental delay or intellectual disability

• Distinctive facial features

• Congenital anomalies: Including heart defects, kidney malformations, or skeletal abnormalities

• Growth retardation or short stature

• Seizures or neurological issues

• Behavioral problems: Such as hyperactivity, aggression, or autism-like traits

• Endocrine abnormalities: In some types (e.g., genital anomalies, hormonal imbalances)

Each CGS is unique, and the clinical picture depends on the combination of gene losses or duplications.

Diagnosis

Diagnosis of a Contiguous Gene Syndrome requires a combination of clinical evaluation and specialized genetic testing. Diagnostic steps may include:

• Detailed medical history and physical examination: To identify characteristic features and affected systems

• Chromosomal microarray (CMA): The gold standard test that detects microdeletions and microduplications

• FISH (Fluorescence In Situ Hybridization): Used to confirm deletions in specific known syndromes

• Whole exome or genome sequencing: May be used to detect gene-level changes if chromosomal testing is inconclusive

• Targeted genetic tests: Based on suspected clinical syndromes (e.g., 22q11.2 deletion for DiGeorge syndrome)

Treatment

There is no cure for Contiguous Gene Syndromes, so treatment is supportive and tailored to the individual’s specific symptoms. A multidisciplinary team is usually involved. Treatment approaches may include:

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

• Special education services: For children with intellectual or learning disabilities

• Medications: To manage seizures, behavioral issues, or hormonal imbalances

• Surgical interventions: For congenital heart defects, cleft palate, or orthopedic abnormalities

• Regular monitoring: With neurology, cardiology, endocrinology, and genetics specialists

• Psychological support: For both patients and families

• Genetic counseling: To discuss recurrence risks and family planning options

Prognosis

The long-term outlook for individuals with Contiguous Gene Syndromes varies widely based on the genes involved and the severity of associated symptoms. Some children may have mild learning issues and live independently, while others may have complex medical needs and require lifelong care. Early diagnosis and individualized, multidisciplinary management greatly improve developmental outcomes and quality of life. Ongoing research and advances in genetic testing continue to enhance our understanding and care of CGS.