CHARGE syndrome- diagnosis and treatment

CHARGE syndrome- diagnosis and treatment

CHARGE syndrome is the acronym for a rare genetic disease that includes specific congenital defects: coloboma of the eye, heart defects, atresia of nasal choanae, mental retardation, genital and urinary abnormalities, ear abnormalities and deafness. CHARGE syndrome was first described in 1979 by Dr. BD Hall and in 1981 Dr. RA Pagon attributed the term CHARGE to these abnormalities that occur together. It is estimated that CHARGE syndrome affects 1 in 10 000 births.

CHARGE syndrome is an autosomal dominant genetic disorder caused by mutations in the CHD7 gene, located on chromosome 8. CHD7 gene encodes for a protein that is involved in chromatin remodeling. Chromatin is composed of DNA and proteins that are found in various forms of packaging ( nucleosomes, chromosomes etc). CDH7 gene mutations lead to a dysfunctional protein that disrupts chromatin remodeling and regulation of gene expression. All these anomalies that occur during embryonic development lead to malformations in CHARGE syndrome. However, there must be said that in about 25% of CHARGE syndrome patients scientists cannot identify a mutation in the gene CDH7. Therefore it is assumed that there are other genetic or environmental factors that contribute to CHARGE syndrome.

Diagnosis of CHARGE syndrome

CHARGE syndrome patients can get diagnosed at birth on the basis of specific features: coloboma of the eye, ear abnormalities, genitourinary malformations.  The three C’s can indicate CHARGE syndrome: coloboma, atresia choanae and abnormal semicircular canals in the ears. Genetic testing for confirmation is needed, but this is done only in specialized laboratories by geneticists familiar with this disease.

Differential diagnosis can be made with other congenital anomalies including heart or facial defects such as DiGeorge syndrome (including heart abnormalities, facial abnormalities, thymus hypoplasia, cleft palate, and hypocalcemia), Smith-Lemli-Opitz syndrome ( specific facial features, syndactyly, polydactyly, cleft palate, hipopasdias, mental retardation) or velocardiofacial syndrome (heart defects, abnormalities of the thymus and parathyroid glands and typical facial features). There can be done various tests to rule out other diseases such as high-resolution karyotype, blood tests, imaging investigations etc.

Treatment of patients with CHARGE syndrome

CHARGE syndrome patients need special care at birth because they have multiple health problems. Doctors should look for and correct life threatening abnormalities (atresia of nasal choanae, heart defects, etc.). It is possible that over time be required several surgical interventions to correct birth defects. In addition, because of mental and communication disabilities ( low IQ, mental retardation, poor learning abilities ), physical, occupational and speech therapies should be considered.