Harrington syndrome also called as DiGeorge syndrome is a congenital immunodeficiency characterized by abnormal facies, congenital heart defects, hypoparathyroidism with hypocalcaemia, cognitive, behavioral, and psychiatric problems, and increased susceptibility to infections.

 

Causes

• Harrington syndrome is found to have a microdeletion of 22q11.
• Particularly affecting development of the third and fourth branchial pouches (pharyngeal pouches).
• This affects the thymus gland and parathyroid glands, responsible for regulation of blood calcium levels.
• It’s inherited as autosomal dominant, autosomal recessive and X-linked fashions.

Signs and symptoms

• Endocrine- Hypoparathyroidism leading to hypocalcaemia usually begins in the neonatal period, occasionally manifesting in the form of tetany or tonic convulsions.
• Palatal abnormalities- cleft palate, submucosal cleft palate, and velopharyngeal incompetence
• Cardiac manifestations- The most common cardiac anomalies included tetralogy of fallot, ventricular septal defect, pulmonary atresia/ventricular septal defect and truncus arteriosus.
• Immunology- Thymic hypoplasia or aplasia leading to defective T-cell function is the hallmark of DiGeorge anomaly.
• Hearing loss- conductive and sensorineural hearing loss
• Other manifestations- growth retardation, behavioral, psychiatric, , communication disorders, and significant feeding problems
• Infections- Increased susceptibility to infections like pneumocystis carinii, fungal infections and viral infections
• Association with other autoimmune disease- Graves disease, rheumatoid arthritis, and immune thrombocytopenic purpura

Tests and diagnosis

• Micro deletion of chromosomes can usually be detected in 2-3 days by fluorescent in situ hybridization (FISH) and rapid PCR techniques
• Assessment of parathyroid function – Low calcium levels
• Lateral view of chest X-ray- Thymic aplasia or hypoplasia
• 2D- echo to detect cardiac anomolies

Treatment

Hypoparathyroidism and hypocalcemia are managed with calcium and vitamin D administration.

Treatment of immunodeficiency- Early thymus transplantation (ie, before the onset of infectious complications) may promote successful immune reconstitution.

Surgical care- Correct cardiac malformations per standard surgical techniques. Obtain early consultation with a cardiologist and immunologist to evaluate disease manifestations.