This syndrome is inherited in an autosomal recessive manner. Several mutations in the FIG4-encoding gene were found to cause<unk> . Some of these mutations result in complete loss of protein function; others involve amino-acid replacements at highly conserved residues. Not all mutations in the FIG4 gene result<unk> . Some mutations lead to various forms of Charcot–Marie–Tooth disease, Amyotrophic lateral sclerosis 11, and bilateral temporooccipital polymicrogyria. Patients affected with<unk>  are homozygous, compound homozygous, or compound heterozygous for deleterious mutations in FIG4. Animal model Spongiform degeneration of mouse brains caused by altering PI3P to PI(3,5)P2 conversion is associated with human Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis (ALS) by accumulation of Lc3II, p62, and LAMP2 proteins, which also contributes to inclusion body disease. Manipulation of this signaling lipid involves culturing fibroblasts obtained by insertion of ETn2-beta(early transposon 2-beta) into intron 18 of FIG4 gene in vacuolar membrane of mice labeled pale tremor (plt). These fibroblasts fill with immunoreactive large vacuoles; but more importantly their abnormal concentration of PI(3,5)P2 demonstrates conserved function of mammalian FIG4 and late endosome-lysosome axis failure responsible for lack of apoptosis of neurons and Schwann cells (but large motor axons are still lost while demyelination still happens). In contrast, homozygous FIG4 defective (FIG4-/-) mice have a reduction of myelin, especially in optic nerves; but this detriment is rescued by an overexpression of human FIG4 I41T at low-level function. While FIG4-null adult mice have macroscopically normal brains with increments in apoptosis and neuronal density with delayed cell maturation, neonatal mice maintain all neurologic defects. FIG4 expression in mouse brain cells is also comparable to that of calvaria, osteoblasts, and bone marrow cells.
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