Table of Contents
CHARGE Syndrome: Definition
CHARGE (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) syndrome is a rare autosomal dominant disorder in children. Midline structures of an affected person show more abnormalities. The incidence of CHARGE syndrome is 1 in 9,000–12,000 newborns.
Coloboma is a hole in the structures of the eyes. It occurs in 70%–80% of all cases and can present unilaterally or bilaterally. The choroid, retina, iris, and optic disc are the sites of occurrence. There is an impairment of vision depending on the location and size of the hole or gap. Children suffering from this syndrome can also have small eyes (microphthalmia).
Heart defects occur in 60%–70% of cases. They include coarctation of the aorta, aortic valve stenosis, tetralogy of Fallot, and patent ductus arteriosus. Other structural defects can also occur.
Choanal atresia affects 30%–60% of all cases. It is a condition in which the nasal passages become completely blocked. A less mild form is choanal stenosis, in which the nasal passages become narrowed.
Growth retardation occurs in almost all cases. Affected children fail to thrive. This becomes noticeable in the first 6 months of life. The underlying endocrine causes a growth hormone and gonadotrophin deficiency that is responsible for the growth retardation.
Genital abnormalities: Most children experience hypogonadotropic hypogonadism. Micropenis and cryptorchidism (undescended testis) can be common abnormalities in males. Females are less commonly affected; labial dysplasia is a common defect. About 70% of males and 30% of females suffer from these disorders.
There is malformation of external ears in all cases. The ears are small and cup-shaped with protruding helices. Middle ears and inner ears have developmental defects that can impair the child’s ability to hear.
Other common abnormalities include the following:
- Dysmorphic features such as a square face, facial nerve palsy, malar flattening, and micrognathia
- Neurological anomalies
- Renal anomalies
- Orofacial clefting
- Tracheoesophageal fistula
- Polydactyly or oligodactyly
- Intellectual disability
Major Clinical Features
|Ocular coloboma||Unilateral or bilateral coloboma|
|Choanal atresia/stenosis||Unilateral/bilateral bony or membranous choanal atresia or stenosis|
|Cranial nerve abnormality||Facial palsy, hypoplasia of auditory nerve|
|Ear abnormalities||Ossicular malformation, cochlear defects, temporal bone abnormalities|
|Cardiovascular||Tetralogy of Fallot, atrioventricular canal defects, aortic arch anomalies|
|Growth||Short stature (occasional growth hormone deficiency)|
|Facial features||Square face with a broad prominent forehead, prominent nasal bridge, flat mid face|
|Other||Tracheoesophageal fistula, cleft palate|
Mutations occur in the CHD7 gene. CHD7 plays an important role in embryonic development by producinga protein (CHD7 protein) that is involved in a process called chromatin remodeling. Chromatin is a complex of proteins and DNA that molds the DNA into the shape of chromosomes. Chromatin remodeling controls gene expression. Due to gene mutation in this syndrome, the defective CHD7 protein breaks down prematurely. The shortage of this protein results in disrupted chromatin remodeling and poor gene expression and leads to various developmental defects.
The presence of a single copy of a mutated gene in all cells causes the syndrome.
Mortality and Morbidity
- Mortality is higher in the neonatal period and early infancy.
- Swallowing problems increase the risk of aspiration.
- Reasons for increased mortality include cyanotic heart disease, bilateral choanal atresia, esophageal atresia, and central nervous system anomalies.
Diagnosis can be made from the patient’s medical history, physical examination, and investigations.
- Prenatally: intrauterine growth restriction, congenital heart defects, poor fetal movements, and orofacial clefting
- Neonatal period: dysmorphic features, small for gestational age, impaired hearing tests, and an inability to pass the nasogastric tube
- Infantile period: poor growth, developmental delay, and feeding difficulties
Typical features of CHARGE syndrome include coloboma, heart anomalies, choanal atresia, retardation of growth, and genetic and ear anomalies.
- Complete blood count
- Renal function tests
- Analysis of CHD7 mutation
- Hormonal analysis (luteinizing hormone-releasing hormone, human chorionic gonadotropin, growth hormone)
- Immunological studies
- Other tests that can be performed include electroencephalogram, electrocardiogram, and audiometry and ophthalmologic tests.
- Chest radiographs: to detect cardiopulmonary abnormalities
- Cranial ultrasonography: to exclude major brain malformations (performed in the neonatal period)
- Barium swallow: to diagnose esophageal dysmotility
- Computed tomography scan and magnetic resonance imaging of the head: used to detect forebrain anomalies, cerebral atrophy, and midbrain defects
- Echocardiography: used to detect valvular abnormalities and structural heart defects
- Abdominal ultrasonography: to exclude renal abnormalities
- Skeletal survey: to exclude skeletal anomalies
Management is based on medical and surgical measures.
At birth, the following measures should be taken:
- Oxygen supplementation: for cyanotic heart disease
- Nasogastric feeding: for swallowing difficulties
- Artificial tears: in facial palsy to avoid scarring of a cornea
- Androgen therapy: given in some cases for penile growth
VACTERL Association: Definition
VACTERL (vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities) association is a rare genetic disorder that causes a group of birth defects. It occurs in 1 of every 1,000–40,000 newborns. The disease affects the median and paramedian structures. Other terms such as VATER or VACTERL are also used for the same disorder.
Abnormalities include the following:
- Facial asymmetry
- Lung defects
- Ear malformation
- Intestinal malrotation
- Genital abnormalities
Mental functioning is normal.
VACTERL association is a complex condition comprising a number of genetic and environmental factors. The exact genetic changes have not been identified in detail.
The condition follows a sporadic pattern; there is no clear inheritance pattern. Family members may exhibit some characteristics, but not all of them need to be diagnosed as having VACTERL.
Medical therapy includes supportive therapy such as oxygen and nasogastric intubation.
Operative therapy is based on the surgical correction of structural abnormalities, including tracheoesophageal fistula, valvular malformations, and anal artesia.
- Spinal ultrasound
- Spinal X-ray
- Renal ultrasound
- Observation for respiratory distress or feeding problems