Clinical Analysis Of 31 Patients With X-linked Adrenal Hypoplasia Congenital Caused By DAX-1 Gene Mutation

Objective: To discuss the clinical phenotype aspects,the relevance between genetype and clinical phenotype and therapeutic outcome,by analysis of the clinical manifestations and gene molecular changes of 31 patients with X-linked adrenal hypoplasia congenital(XL-AHC)caused by DAX-1 gene mutation.Methods: To gather the clinical means of 31 patients with XL-AHC diagnosed in the Children’s Hospital of Chongqing Medical University from December 2006 to December 2019.Including clinical manifestations,lectrolyte anned hormo levels,imaging examinations,gene sequencing,treatment and follow-up.Results:(1)31 patients were male,age of initial visit ranging from the neonatal period to 12 years and 6 months,age of onset from the neonatal period to 8 years and 6 months.Eight of them have a clear family history.(2)The main symptom of onset was adrenocortical hypofunction,including skin pigmentation,difficulty feeding,no weight gain,vomiting.7 cases of them with adrenal crisis(22.6%).(3)18 patients were in mini-puberty and had a normal testosterone level.(4)5 patients with precocious puberty,3 of them self-remissions in 2 years.The other two cases were brothers of the same family.The elder brother developed precocious puberty after birth,which self-remission at the age of 3.Now,he has entered puberty and developed HHG.The younger brother developed precocious puberty after birth,has a 12.7 years old bone age at the age of 8 years and 3 months,mini-puberty continued to progress,and he is in the treatment of GnRHa.(5)4 patients entered puberty and developed HHG,and were induced puberty by testosterone undecanoate.(6)3 cases were diagnosed as Xp21 near gene deletion syndrome.(7)Genetic testing of 31 patients and 11 genetic mutations were unreported: c.766G>T,c.1215G>A,c.994G>T,c.151＿160del,c.664 del AC,c.1382 del T,c.585＿595del TCTGTACCGCT,c.850＿851ins AGC,X chromosome 2.2M deletion,X chromosome short arm size about 424 Mb deletion,c.1129G>C.Conclution: Most of the patients with XL-AHC reported onset within two months after birth,mainly manifested as adrenocortical hypofunction.Although HHG occurred in 4 patients who entered puberty,the testosterone level was normal in patients who were in the mini-puberty.There is a certain correlation between genotype and clinical phenotype.One of the patients with precocious puberty in this group continued to 8 years and 3months old without remission,which is under GnRHa treatment now.One of our patients had a late-onset and mild phenotype missense mutation c.1129G>C(p.Glu377Gln),and it was not been reported before.Combined with the clinical characteristics,it is speculated that it may be pathogenic,but it needs to be further confirmed by the protein function test of the mutation site.This study found 11 unreported gene mutation sites,which enriched the gene mutation spectrum and provided help for genetic counseling and prenatal diagnosis.