Also known as multiple congenital anomalies-hypotonia-seizures syndrome; it belongs to a group of disorders called glycosylphosphatidylinositol (GPI-) anchor defects
A rare, multisystemic, inherited, glycosylphosphatidylinositol anchor defect disorder caused by a mutation in the gene PIGN disrupting protein glycosylation. Symptoms typically manifest in infancy, including global developmental delay, hypotonia (low muscle tone), seizures, facial dysmorphism (abnormal difference in structure), underdeveloped fingertips, gastrointestinal reflux, cerebellar atrophy (deterioration of neurons), small corpus callosum (the area of the brain that connects the two cerebral hemispheres), cerebral volume loss, abnormal or delayed myelination (the process of forming a myelin sheath around a nerve), congenital heart disease, renal anomalies, hepatosplenomegaly (enlargement of the liver and spleen), scoliosis (abnormal curvature of the spine), and abnormal movements.
Symptoms
Individuals with PIGN-CDG universally have severe developmental delay, hypotonia, and seizures. They frequently have abnormal facial features, underdeveloped fingertips, GI reflux, cerebellar atrophy, small corpus callosum, cerebral volume loss, abnormal or delayed myelination, and may require feeding tubes. They occasionally have congenital heart disease, renal anomalies (including renal dysplasia and cortical cysts), hepatosplenomegaly, scoliosis, and abnormal movements (choreoathetosis, extrapyramidal dyskinesia). There is a large clinical spectrum associated with PIGN-CDG, with the most severe being intrauterine death due to congenital anomalies. Those who are mildly affected may have isolated developmental delay and intellectual disability.
Diagnosis
The primary screening tool for PIGN-CDG is testing for the presence of GPI-anchored proteins on the surface of granulocytes (a subset of white blood cells). This can be tested by a method called flow cytometry in the patient’s blood. The ultimate diagnosis is genetic testing in blood. Individuals with PIGN-CDG have two faulty copies of the PIGN gene.
Treatment and Prognosis
To date, there are no known specific treatment options for PIGN-CDG. Treatment is aimed at the management of symptoms and the prevention of complications. Most diagnosed PIGN-CDG patients are still young, which makes long-term prognosis difficult.