Noonan syndrome (NS)-associated LZTR1 variants may be inherited in an autosomal dominant manner or an autosomal recessive manner in different families and there is overlap between the variants identified in people with NS or schwannomatosis, although schwannomas are not a feature of Noonan syndrome. NS is caused by dysregulation of the RAS-MAPK signalling pathway and several other genes have been associated with the condition, including PTPN11, KRAS, SOS1, RAF1, SHOC2, NRAS, CBL, BRAF, MAP2K1, RIT1, RASA2 and SOS2.
Schwannomatosis-associated LZTR1 variants are inherited in an autosomal dominant manner. Pathogenic loss-of-function LZTR1 variants have been identified in various parts of the gene and somatic loss of the wildtype allele is frequently seen in LZTR1-related schwannomatosis associated tumours. However, there is incomplete penetrance of the disorder and unaffected mutation carriers can be found in schwannomatosis families.
LZTR1