Townes-brocks Syndrome Associated With SALL1 Gene Mutation:A Report Of 2 Cases And Review Of The Literature

Background: Townes-Brocks syndrome(TBS)is a rare autosomal dominant congenital anomaly syndrome,which is characterized by developmental deformity of anus,limbs and external ear and hearing loss,and may have abnormal kidney.At present,some studies have shown that TBS is the result of mutation of development gene spalt-like transcription factor 1(SALL1).Result: We reported 2 children with Townes-Brocks syndrome,both of whom started from kidney diseases,and other system malformations were found by tracing the medical history.Gene detection showed that SALL1 had nonsense mutation(c.1273C>T,p.Q425X)and SALL1 had frame shift mutation(c.1111＿1121 del,p.S371Lfs* 15).By reviewing the reported 28 case reports or literature review,we summarized the renal pathological data of 133 children with TBS syndrome,including 2children in this study.Among them,44 cases(33%)had abnormal renal function and 72 cases(54%)had abnormal renal structure,of which renal dysplasia was the main manifestation,accounting for more than 70% of all renal structural abnormalities.We also found that 7 patients had a rare phenotype-congenital hypothyroidism.Conclusion: Two new mutation sites(c.1273C>T,c.1111＿1121 del)which caused the mutation of SALL1 gene in TBS syndrome were found,and the results of pathogenicity analysis showed that they were consistent with pathogenicity variation.The clinical manifestations of TBS are highly variable.Besides the typical anal,limb and external ear deformities,renal lesions are also a common phenotype,including abnormal renal structure or function.At the same time,we found that hypothyroidism may be caused by the mutation of SALL1 gene affecting the expression of PAX8 gene,and then affecting the growth and development of thyroid.