CHARGE Syndrome

Definition

CHARGE syndrome is a rare genetic anomaly cause congenital deformities in the multiple vital organs of the body. This medical condition often arises without hereditary involvement. The complexity of the disease is not similar in every case. The common problem in charge syndrome is a child born with fetal cardiac complications along with breathing difficulty. Prolonged hospital stay and multiple surgeries, even do not control all the related intricacy.

The term CHARGE denotes:

C (coloboma )- this stands for a puncture in the anatomical structure of the eye anatomy, mainly retina and specific cranial nerves are involved.

H (Hear defects) –  Mainly four abnormalities are detected, which include a puncture in the ventricles, an obstacle between the heart  and lungs, the major blood vessel (aorta) extends over the puncture of the ventricles, the muscle lining surrounded the right ventricle becomes thickened; combinations of these four anomalies are termed as Tetralogy of Fallot.

A (atresia of the choanae) – Partial or complete obstruction in the nasal breathing passages.

R – Retardation of physical and mental development

G – Genital rudimentary development due to gonadotropic hormone insufficiency.

E – Middle and inner ear defects and hearing loss due to responsible nervous system abnormality. (1,2,3)

History

In 1979, Hall et al. first illustrated the close association of the choanal atresia with the multiple congenital abnormalities (as explainsed in CHARGE syndrome) and in the latter part of the same year Hittner described ocular colobomas with the multiple congenital abnormalities. Therefore, the syndrome was termed as Hall-Hittner syndrome. In 1981, Pagon et al., first invented the term CHARGE syndrome, depending upon discriminative symptomatic association of abnormalities taking place collectively more often than individual would anticipate on the prospective basis.

The presence of four among six mentioned symptoms is main diagnostic criteria for CHARGE syndrome. Over a decade clinician are jot down the pattern of symptoms which are closely associated with Charge syndrome. (1,5)

CHARGE Syndrome Symptoms

The considerable typical CHARGE syndrome is combination of Coloboma, Cranial nerve abnormalities, Choanal atresia.

Coloboma

The symptoms associated with colombia are:

• Impaired vision (myopia and/or far-sightedness)
• Photophobia (sensitive to bright light)
• Complete Blindness

These symptoms arise due to small puncture in pupil (iris coloboma) and/or defective retina, macula or optic nerve.

Cranial nerve abnormalities

• Abnormalities in Vestibulocochlear nerve (cranial nerve VIII) lead to mild defects in the audible range to complete deafness. In most of the diagnostic imaging system discloses a hypoplastic cochlea means the reduced size of the apical turn along with smaller length than the normal of the basal turn. Often semicircular canal is absent. Loss of hearing and trouble in balancing the body is the familiar features allied with cochlear hypoplasia. External ear often tends to obtrude and lack lobes in CHARGE syndrome.
• The Glossopharyngeal and Vagus Nerves (Cranial nerve IX and X) abnormality can cause swallowing difficulty. There is a coordination problem between sucking and swallowing and often leads to entering the food into the lungs and may cause pneumonia.
• Due to the facial nerve and vestibular nerve anomalies may lead to paralysis of one side of the face (asymmetric facial palsy) and resulting from this lack of facial expression.
• Abnormality in Olfactory nerve (Cranial nerve I ) associated with absence of smell sensation, and due to this the normal eating habit formation become difficult for an affected child.

Choanal atresia

The blockade of the inner nasal passage opening leads to obstruction of the nasal passage with the rest of the respiratory canal is called Choanal atresia. During fetus develops in the womb, due to incomplete canalization at the inferior aspect of the palate, which is sited between the nose and the oral cavity is caused the development of the Choanal atresia. Choanal atresia can develop at single or both the sides of the nasal cavity, but more frequent in right side.

The narrowing or complete blockage of the one sided nasal canal can be imperceptible after a few years of birth or it provides chronic bulky discharge from one side of the nose. But if the blockage present in both the sides, then it produces significant breathing and feeding difficulty in the newborn infant. Other common symptoms are noisy breathing, aspirate milk and turn blue during sleeping or feeding. The patient usually opens his or her mouth during the awakening condition for allowing air into reach to the lungs, and temporary symptomatic relief may obtain.

Miscellaneous symptoms

Other than the major symptoms, some symptoms may occur in minor form or occasionally like

defective cardiovascular development, genital hypoplasia, cleft lips, or palate, growth retardation, cognitive impairment. In rare cases, renal abnormality, spine deformity, structural and functional problem of skeletal system, including hand, neck, shoulder abnormalities. (4,5)

Cause

Usually CHARGE syndrome develops intermittently. The abnormal mutation in the CHD7 gene is the major cause of the development of the CHARGE syndrome. In addition, findings also supports that genomic alterations occur at the site of the CHD7 gene. The identified location of the CHD7 gene is in the region of chromosome 8 (8q12.2). (4)

Incidence rate

Charge syndrome is a rare syndrome, the live birth cases are 0.1-1.2 per 10,000. The incidence rate is same for both the gender. In minor symptomatic approach often leads to misdiagnosis or undiagnosed at the initial stage. Correct diagnosis is possible after a few weeks or months, when all the symptoms are apparent. (1,4, 5)

Differential diagnosis

Genetics

• For confirming the integrity of 22, 14, and 9 chromosomes Karyotype test is performed.
• FISH (Fluorescentin situ hybridization) test is conducted for diagnosing the 22q deletion
• Currently Molecular technologiesare used for CHD7 gene mutation testing.

Blood test

To access the renal function and for rejection of hypocalcemia, blood tests conducted for estimating the creatinine, urea nitrogen, electrolytes and calcium.

Endocrinal tests

Within the first four months or at the age of puberty, Luteinising Hormone Releasing Hormone (LHRH) and Human Chorionic Gonadotropin (HCG) tests should be made to assess for the genital hypoplasia.

Growth hormone (GH) stimulation levels should be investigated for checking the involvement in the growth retardation.

X-ray also periodically performed to tract the growth of the affected child.

Auditory test

This test is conducted for estimating the range of the hearing loss.

Cardiac tests

Echocardiogram and Holter monitoring are conducted for identifying the problem of the heart and also exclude the possibility of congenital heart disease.

Vision test

Different vision related tests are performed to measure the severity of the vision problem.

Imaging tests

MRI, CT scans and other radio-imaging tests are performed to check the involvement of the cranial nerve abnormality. (1,5)

Treatment

The multiple organ deformities are Involved in Charge syndrome, therefore no particular therapy is available for treating the syndrome. Various surgical intervention can help to correct some associated symptoms, but usually patient need medical and other supportive measures for lifelong.

Researchers try hard to develop novel medical approach to treat Charge patients, but all advancements are yet under trial stage. (4)

References

1. CHARGE Syndrome; Retrieve from: http://www.chargesyndrome.org/about-charge.asp
2. CHARGE syndrome; Genetic Home Reference; Retrieve from: https://ghr.nlm.nih.gov/condition/charge syndrome
3. CHARGE Syndrome, (2015); WebMD Medical Reference from the National Organization for Rare; Retrieve from: http://www.webmd.com/children/charge-syndrome-10769
4. CHARGE Syndrome (2015); National Organization for Rare Disorders; Retrieve from: http://rarediseases.org/rare-diseases/charge-syndrome/
5. Kim D Blake and Chitra Prasad (2006); CHARGE syndrome; DOI: 10.1186/1750-1172-1-34; Retrieve from: http://ojrd.biomedcentral.com/articles/10.1186/1750-1172-1-34