CHARGE syndrome

Overview

CHARGE syndrome is a rare genetic disorder that affects multiple organ systems and is characterized by a specific set of birth defects. The acronym “CHARGE” stands for:

• Coloboma of the eye

• Heart defects

• Atresia of the choanae (nasal passages)

• Retardation of growth and/or development

• Genital abnormalities

• Ear anomalies and/or hearing loss

First described in the 1970s, CHARGE syndrome has since been recognized as a complex condition with a wide range of clinical features. The severity of symptoms varies greatly among individuals, and early diagnosis and multidisciplinary care are essential for improving outcomes.

Causes

CHARGE syndrome is primarily caused by mutations in the CHD7 gene located on chromosome 8. This gene plays a crucial role in the development of various tissues and organs during early fetal development. Most cases result from new (de novo) mutations, meaning they are not inherited from either parent. However, in rare cases, CHARGE syndrome may follow an autosomal dominant inheritance pattern if one parent carries the mutation.

Symptoms

Symptoms of CHARGE syndrome can vary widely and affect multiple systems. Common features include:

• Coloboma: A gap or defect in one of the structures of the eye (iris, retina, or optic disc), which may affect vision

• Heart defects: Such as tetralogy of Fallot, atrial septal defect (ASD), or ventricular septal defect (VSD)

• Choanal atresia: Blockage or narrowing of the nasal passages, leading to breathing difficulties in newborns

• Growth delay: Poor weight gain and short stature

• Developmental delay: Including delays in motor skills, speech, and cognitive abilities

• Genital abnormalities: Undescended testes in males or small labia in females

• Ear abnormalities: Malformed outer ears, frequent ear infections, and hearing loss (sensorineural or conductive)

• Swallowing and feeding difficulties: Often requiring feeding tubes in infancy

• Balance issues and low muscle tone: Due to inner ear malformations

Diagnosis

Diagnosis of CHARGE syndrome is based on clinical findings, genetic testing, and imaging studies. The diagnostic process includes:

• Clinical evaluation: Based on a combination of major and minor diagnostic criteria

• Genetic testing: Sequencing of the CHD7 gene to confirm the presence of a mutation

• Imaging:

  • MRI or CT scan of the brain and ears to assess anatomical anomalies

  • Cardiac ultrasound (echocardiogram) to detect heart defects

  • Endoscopic evaluation to confirm choanal atresia

• Hearing tests: Audiometry or newborn hearing screening

• Vision assessment: To identify colobomas or other ocular issues

Treatment

There is no cure for CHARGE syndrome, and treatment focuses on addressing the individual symptoms and complications through a multidisciplinary approach. Common interventions include:

• Surgical correction: For heart defects, choanal atresia, and genital anomalies

• Feeding support: Including feeding therapy and gastrostomy tubes when needed

• Speech and language therapy: To assist with communication and feeding

• Physical and occupational therapy: For improving mobility, strength, and coordination

• Hearing aids or cochlear implants: For hearing loss

• Vision aids and special education services: For children with visual impairment or developmental delays

• Endocrinology support: For growth hormone therapy or management of puberty-related issues

• Psychological and behavioral support: For managing developmental and emotional challenges

Prognosis

The prognosis for individuals with CHARGE syndrome varies widely depending on the severity and combination of symptoms. Some children may have life-threatening issues in infancy, especially related to heart defects or breathing difficulties. However, with early intervention and comprehensive care, many individuals with CHARGE syndrome live into adulthood and lead fulfilling lives. Long-term management often includes ongoing medical care, special education, and support services tailored to the individual's unique needs.