Introduction: 21-hydroxilase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia. Mutations of CYP21A2 induces 21OHD, a rare autosomal recessive manner. CHARGE syndrome (CS) is a rare autosomal dominant manner that is typically caused by heterozygous chromodomain helicase DNA binding protein-7 (CHD7) mutations. Here, we report the combination cases with genetically diagnosing 21OHD and CS at the first time.
Case: The patient is a boy at the age of 7 years. He had no problems in prenatal period. His parents had no consanguinity. Though he had no symptoms of 21OHD such as pigmentation of scrotum at birth, he was carefully followed up after birth because of his brother suffered from 21OHD. At the age of 9 days, he showed electrolyte abnormality, hypoglycemia and high values of 17-hydroxyprogesterone: 18.3 ng/ml (<3.5 ng/ml). He was clinically diagnosed with 21OHD and treated by fludrocortisone acetate and cortisol. Genetic analysis was performed, and identified compound heterozygotes mutations as IVS2-13A/C>G/I172N in CYP21A2. These mutations were the same of his brother. He showed various complications such as cleft lip and palate, bilateral severe deafness, congenital heart disease (ventricular heart septal defect, patent ductus arteriosus), tracheomalacia, gastroesophageal reflux disease and cryptorchidism. These were not common features with 21OHD, thus he was suspected with CS. At the age of 5 years, we performed genetic analysis of CHD7. A de novo variant in a CHD7 splicing acceptor site (NM_017780.3: c.71654A>G) was identified. At last, he was genetically diagnosed with a combination case of 21OHD and CS.
Discussion: The incidence of 21OHD and CS is from 1:10 000 to 20 000, and 1:20 000, respectively. Both 21OHD and CS are rare diseases. The case of combination with 21OHD and CS has not been reported previously. We consider that this case occurs accidentally. When the patients have atypical symptoms, we may should consider that they have another diseases addition to primary disease.
Conclusion: We report a first combination case of 21OHD and CS confirmed by genetic analysis.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology