Abstract
Context: CHARGE association consists of congenital malformation of Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies and/or deafness. It is often caused by CHD7 gene mutation, which also one of the causative gene for Kallmann syndrome. The endocrine dysfunction in CHARGE association has been reported but not fully understood. Objective: To clarify the mode of growth and frequency of endocrine dysfunction in CHARGE association. Subjective: We investigated the characteristics of growth and puberty, and endocrine function in 23 children (15 males and 8 females, 0~20 years old) with CHARGE association. Results: The birthweight was from -2.74 to +1.14 SDS and the birth length was from -2.86 to +1.10 SDS. 5 children were born small for gestational age. The height below -2SDS in 18 children. GH secretion was evaluated in 11 children with short stature (-9 to -2.3SD) except for one with normal height (-0.3 SD in 6 years old girl); 5 children including one with normal stature were revealed to have GH deficiency. One short girl with GH deficiency previously showed normal GH response to provocation test at 1 year old but has developed to be GH deficient at 7 years old. Gonadotropin-releasing hormone loading tests were performed in 7 males and 3 females. Nine out of 10 children showed hypogonadotropic hypogonadism; one girl showed hypergonadotropic hypogonadism, whose ovaries were undetectable on ultrasound. Human chorionic gonadotrophin (HCG) tests were performed in 6 males with micropenis and/or cryptorchidism. Peak testosterone levels after HCG stimulation were from 0 to 6.99 ng/ml. 4 patients showed peak testosterone levels less than 1 ng/ml. Four boys showed combined gonadotropin deficiency and primary hypogonadism. Conclusions: Our data showed the diversity of endocrine function in children with CHARGE association. GH deficiency can be developed over time. Hypogonadotropic hypogonadism is common, while isolated/combined primary hypogonadism should be taken into consideration in children with CHARGE association.