Objective To discuss clinical characteristics of a
family with
Andersen-Tawil syndrome, test and analyze the
mutation of their pathogenic
gene, and to discover the dependency of
genotype and
phenotype by searching every reported
Andersen-Tawil syndrome patient in all accessible
literature worldwide.
Methods In December 2nd,2016,two
patients in the Department of
Neurology,the First
Hospital of Shanxi Medical
University, received medical
history data collection and relevant examinations.
PCR and
DNA sequencing were applied to detect
ion channel diseases related
genes such as SCN4A, CACNA1S, KCNJ2, KCNE3, KCNE4, KCNJ18, KCNJ5.Random selection of 200
healthy volunteers from Shanxi Medical
University served as normal controls.
Andersen-Tawil syndrome cases,which are accorded with statistical criteria in published
literature, were collected.Their
genotype and
phenotype were analyzed and summarized.Results Clinical manifestation of the pre-confirmed
patient and his
father was accorded with diagnostic criteria of
Andersen-Tawil syndrome.Prominent characteristics included ventricular
arrhythmia, periodic
paralysis, and dysmorphic features.The two
patients had
renal tubular acidosis.One of these two
patients also had increased level of
renin-
angiotensin-
aldosterone.New
mutation Q164R in the KCNJ2
gene was found in these two
patients.There was no
report in any
literature or any database that we could find about this
gene mutation at present.The
mutation was not found among other healthy
family members and 200 healthy controls.In this study,we referenced 55 samples of
Andersen-Tawil syndrome in 12 articles,in which 54 samples are KCNJ2
gene mutation,one is KCNJ5
gene mutation.We concluded a negative correlation between the
onset age of periodic
paralysis and the
onset age of cardiac symptoms after a
statistical analysis of these 54
patients with KCNJ2
gene mutation(rs=-0.698 1,P=0.005 5).The
incidence of cardiac symptoms in
patients of
Andersen-Tawil syndrome with periodic
paralysis was reduced(33.33%(14/42)vs 9/11, χ2=6.485,P=0.011).
Men(96.00%(24/25))were found more likely to have periodic
paralysis than
women(65.52%(19/29); χ2=7.691,P=0.006).
Women (64.29%(18/28))were found more likely to have cardiac symptoms than
men(20.00%(5/25); χ2=10.545,P=0.001).Conclusions New
mutation Q164R in the KCNJ2
gene is the cause of
Andersen-Tawil syndrome,which could cause
renal tubular acidosis.We speculate that the
gene may
play a
role in the way of
potassium regulating
aldosterone.For
women with the KCNJ2
gene mutation and the late-onset of periodic
paralysis,it is important to take
drug or manual intervention as early as possible to prevent the occurrence of cardiogenic adverse events.