CHARGE Syndrome: Introduction

CHARGE syndrome is a rare genetic disorder characterized by a specific pattern of birth defects. The acronym "CHARGE" stands for the major features of the syndrome:

• Coloboma of the eye
• Heart defects
• Atresia of the choanae
• Retardation of growth and development
• Genital hypoplasia
• Ear abnormalities and deafness

Key points:

• Inheritance: Autosomal dominant
• Prevalence: Estimated at 1 in 10,000 to 15,000 newborns
• Primary gene involved: CHD7 (chromodomain helicase DNA-binding protein 7)

Clinical Features of CHARGE Syndrome

Ocular Abnormalities:

• Coloboma (70-80% of cases)
• Microphthalmia
• Strabismus

Cardiovascular Defects:

• Tetralogy of Fallot
• Ventricular septal defects
• Atrial septal defects
• Patent ductus arteriosus

Choanal Atresia/Stenosis:

• Unilateral or bilateral
• Can cause respiratory distress in newborns

Growth and Developmental Delays:

• Short stature
• Delayed motor milestones
• Intellectual disability (variable severity)

Genital Hypoplasia:

• Micropenis in males
• Undescended testes
• Hypoplastic labia in females

Ear Abnormalities and Hearing Loss:

• External ear malformations
• Middle ear abnormalities
• Sensorineural and/or conductive hearing loss

Additional Features:

• Cranial nerve abnormalities
• Cleft lip and/or palate
• Tracheoesophageal fistula
• Kidney abnormalities
• Characteristic facial features

Diagnosis of CHARGE Syndrome

Diagnosis is based on clinical features, imaging studies, and genetic testing.

Clinical Diagnostic Criteria:

Blake et al. (1998) and updated by Verloes (2005) proposed diagnostic criteria:

• Major criteria: coloboma, choanal atresia, characteristic ear abnormalities
• Minor criteria: rhombencephalic dysfunction, hypothalamo-hypophyseal dysfunction, abnormal middle or inner ear, malformation of mediastinal organs, intellectual disability

Imaging Studies:

• CT or MRI of the head and temporal bones
• Echocardiogram
• Renal ultrasound

Genetic Testing:

• Sequence analysis of CHD7 gene
• Deletion/duplication analysis if sequencing is negative

Differential Diagnosis:

• 22q11.2 deletion syndrome
• Kabuki syndrome
• Kallmann syndrome
• Cat eye syndrome

Management of CHARGE Syndrome

Management is multidisciplinary and focuses on addressing specific symptoms and improving quality of life.

Neonatal Period:

• Management of respiratory distress (if choanal atresia present)
• Feeding support (may require gastrostomy tube)
• Cardiac evaluation and management

Ophthalmologic Care:

• Regular eye examinations
• Management of visual impairment
• Monitoring for retinal detachment

Audiologic Management:

• Regular hearing assessments
• Hearing aids or cochlear implants when appropriate
• Speech and language therapy

Developmental Support:

• Early intervention programs
• Special education services
• Occupational and physical therapy

Endocrine Management:

• Growth hormone therapy if deficient
• Management of puberty and fertility issues

Surgical Interventions:

• Repair of choanal atresia
• Cardiac surgery if required
• Cleft lip/palate repair

Ongoing Care:

• Regular follow-up with multidisciplinary team
• Monitoring for scoliosis
• Management of feeding difficulties

Genetic Counseling:

• Discuss inheritance pattern and recurrence risk
• Offer testing for parents and at-risk family members