The mechanism of mutation in FIG4 causing<unk>  involves altering conversion of phosphatidylinositol 3-phosphate (PI3P) to signaling lipid phosphatidylinositol 3,5-bisphosphate(PI(3,5)P2). Because this conversion in endosomal membranes changes dynamically with fission and fusion events to create/absorb intracellular transport vesicles, enlarged cytoplasmic vacuoles have been found in patient neurons, muscle, and cartilage. These have been identified as intracytoplasmic vacuoles(fluid sacs inside cellular cytoplasm) causing excessive build-up of vacuolated macrophages in bone marrow and pericardial fluid in the heart. Fluids may also accumulate in a choroid spaces under the retina, causing central serous retinopathy or chorioretinopathy and possibly vision loss. Paradoxically, overexpression of FIG4 does not yield obvious morphologic phenotype of these fluids accumulating, but alters PI(3,5)P2 levels making cells prone to expansion through dilation of intracellular membranes. Under expression, on the other hand, enhances endosome carrier and formation of vesicles/multivesicular bodies. Central nervous system dysfunction and extensive skeletal anomalies suggest a role for Phosphatidylinositol 3,5-bisphosphate, or PI(3,5)P2, signaling in skeletal development and maintenance.
Yunis–Varon syndrome
Fryns-Aftimos syndrome
Townes–Brocks syndrome
McGillivray syndrome
Berk–Tabatznik syndrome
Helsmoortel-Van der Aa syndrome
CAMFAK syndrome
Van Wyk and Grumbach syndrome