PIGN deficiency is caused by germline mutation in PIGN. PIGN is essential for the eighth step in GPI anchor biosynthesis. GPI-anchored proteins serve critical functions as adhesion molecules, receptors, complement regulators, enzymes and co-receptors in signal transduction pathways. The main clinical features are intellectual disability, developmental delay, hypotonia, epilepsy, and sometimes with multisystem disorder such as liver, renal, cardiac and gastrointestinal involvement. It was previously known as multiple congenital anomalies hypotonia seizure syndrome 1(MCAHS1). A spectrum of phenotypic severity is associated with PIGN variant activities, ranging from Fryns syndrome, characterized by congenital diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphic features, distal digit hypoplasia, at the extreme end, caused by nearly complete loss of function, to MCAHS1 or milder, in which some residual PIGN function may remain.
The prevalence of PIGN deficiency is unknown as it is recently recognized disease, but there have been over 40 patients reported. The PIGN gene is located on chromosome 18q21.33, and PIGN deficiency is an autosomal recessive disorder.
PIGN