Introduction We investigated if ACTN3, ENPP1, ESR1, PITX1 and PITX2 genes which contribute to sagittal and vertical malocclusion also contribute to facial asymmetries and TMD before and after orthodontic and orthognathic surgery treatment. Methods One hundred seventy four dentofacial deformity patients were diagnosed as symmetric or subdivided into four asymmetric groups according to PA cephalometric measurements. TMD exam diagnosis and Jaw Pain and Function-(JPF) questionnaires assessed presence and severity of TMD. Results Fifty two % of patients were symmetric and forty eight % asymmetric. The asymmetry classification demonstrated significant cephalometric differences between symmetric and asymmetric groups, and across the four asymmetric subtypes: Group 1 - mandibular body asymmetry, Group 2 - ramus asymmetry, Group 3 - atypical asymmetry and Group 4 - “C-shaped” asymmetry. ENPP1 SNP-rs6569759 associated with asymmetry Group 1(p=0.004), and rs858339 with asymmetry Group 3 (p=0.002). ESR1 SNP-rs164321 associated with asymmetry Group 4 (p=0.019). These results are confirmed by Principal Component Analysis (PCA) that showed three principal components explaining almost 80% of the variation seen in the studied group. PC1 and PC2 were associated with ESR1 SNP-rs3020318 (p<0.05). Diagnoses of disc displacement with reduction, masticatory muscle myalgia and arthralgia were highly prevalent in the asymmetry groups and all had strong statistical association to ENPP1 rs858339. The average JPF scores for asymmetric subjects before surgery (JPF=7), were significantly higher than symmetric subjects (JPF=2). Patients with asymmetry Group 3 reported the highest preoperative JPF scores and Group 2 and 3 were most likely to be cured of TMD one year after treatment. Conclusions PA cephalometrics can classify asymmetry into distinct groups; identify probability of TMD and genotype associations. Orthodontic and orthognathic treatment of facial asymmetry is very effective at eliminating TMD in most patients.