[Clinical phenotype of Alport syndrome in monozygotic twins]

Objective: To analyze the consistency of the clinical phenotype of Alport syndrome between monozygotic twins. Methods: This retrospective study included identical twins with Alport syndrome who met the inclusion and exclusion criteria and were admitted to Peking University First Hospital from January 2000 to March 2019. Their clinical data and urinary epidermal growth factor (uEGF) level were extracted from the on-line registry system of hereditary kidney diseases, and analyzed retrospectively. Results: Three pairs of monozygotic twins with X-linked Alport syndrome from three non-consanguineous families were included. The consistency of the genotype status between the twins tended to confirm their monozygotic relationship. The first twins were term infants, and the twin 1A had a normal birth weight (2 500 g) while twin 1B was small for gestational age (2 450 g) . The other two pairs of twins were preterm, with different birth weights between twins 2 (2A is 2 450 g, 2B is 1 900 g) , but similar birth weights between twins 3. Although raised in the same environment, compared with twin 1A, 1B had obvious growth retardation. However, growth rate in the remaining twins were consistent. The renal abnormalities were not exactly the same between both twins 1 and twins 2, but was almost the same in twins 3. Both 1A and 1B were characterized by massive proteinuria and renal dysfunction, whereas 1B had worse renal function. At the last follow-up, 1A was diagnosed with stage 3 of chronic kidney disease (CKD) whereas 1B was CKD stage 4. Although renal function in twins 2 were normal, 2A had prominent proteinuria(24 h urinary total protein: 0.22 g) while 2B only had microalbuminuria(urinary albumin-to-creatinine ratio: 65 mg/g). Compared with the age-matched healthy controls, the concentration of uEGF normalized by urine creatinine (uEGF/Cr) were significantly lower in these twins. Besides, the twin-boy who had lower estimated glomerular filtration rates had lower uEGF/Cr. However, the extrarenal manifestations such as ocular and acoustic abnormalities were similar between the twins. Twins 2 and 3 showed bilateral temporal retinal thinning, and twins 1 both had binaural mild mid-low frequency sensorineural deafness. Conclusions: Renal manifestations of X-linked Alport syndrome in monozygotic twins may differ from each other, whereas the extrarenal manifestations including ocular and acoustic abnormalities may be consistent. Low birth weight and growth retardation may be associated with the progression of renal dysfunction.