Lymphangioleiomyomatosis Association with Underlying Genotype in Patients with Tuberous Sclerosis Complex

TSC1 and TSC2 Genotype in Tuberous Sclerosis Complex: Are Other Manifestations of this Multisystem Disease Affected by Genotype?

“…Tian and colleagues looked at the difference in MMPH in patients with TSC2 and TSC1 pathogenic variants as well as in those patients with TSC with no mutation identified (NMI). As opposed to the cystic lung disease, semiquantitative assessment of MMPH did not show any differences in MMPH between patients with TSC2 and TSC1 variants ( 3 ). Further quantitative analysis of these lesions may determine whether there are age and genotype effects on the presence of MMPH or growth of the lesions.…”

“…The age at TSC diagnosis in the adult cohort reported by Tian and colleagues ( 3 ) was 14 years, ranging from 0 to 35 years. TSC is typically diagnosed in the first few years of life, particularly in those presenting with neurological symptoms ( 1 ).…”

“…The cohort reported by Tian and colleagues ( 3 ) had a relatively high percentage of individuals with NMI, accounting for 13/55 or 23% of the individuals. One possible explanation for the inability to identify a pathological variant in these individuals is the presence of mosaicism arising from a postzygotic somatic mutation in a TSC gene.…”

“…In the study reported in this issue of AnnalsATS , Tian and colleagues (pp. 815–819 ) report that in patients with TSC, those with TSC2 pathogenic variants had more severe cystic lung disease than patients with TSC1 pathogenic variants ( 3 ). Those results mirror the findings by Muzykewicz and colleagues ( 4 ), who reported similar observations in patients with TSC.…”

“…In this regard, it has been shown that concentrations greater than 800 pg/ml of serum VEGF-D (vascular endothelial growth factor-D), a lymphangiogenic and angiogenic factor, are diagnostic of LAM and that patients with higher concentrations are more likely to respond to treatment with sirolimus ( 5 ). Tian and colleagues ( 3 ) report that serum VEGF-D concentrations were higher in patients with TSC2 variants than those with TSC1 variants.…”