Our study not only explains the relationship between NFIX mutation (NM_001365902.3(NFIX).164delC (p.Ala55Glyfs*2)) and Malan syndrome from the perspective of genotype-phenotype correlation (the proband showed no Marshall-Smith features like accelerated bone maturation or respiratory distress, but exhibited Malan syndrome characteristics including facial dysmorphism, intellectual disability, and scoliosis), but also elucidates the molecular mechanism through proteasomal degradation leading to NFIX haploinsufficiency. The gene discussed is NFIX; the disease is Respiratory distress.