Advances in Genetic Diagnosis of Kallmann Syndrome and Genetic Interruption.

ABSTRACT

Kallmann syndrome (KS) is a rare hereditary disease with high phenotypic and genetic heterogeneity. Congenital hypogonadotropic hypogonadism and hyposmia/anosmia are the two major characterized phenotypes of KS. Besides, mirror movements, dental agenesis, digital bone abnormalities, unilateral renal agenesis, midline facial defects, hearing loss, and eye movement abnormalities can also be observed in KS patients. Because of the phenotypic heterogeneity, genetic diagnosis become increasingly valuable to distinguish KS from other disorders including normosmic congenital hypogonadotropic hypogonadism, constitutional delay of growth and puberty, CHARGE syndrome, and functional hypogonadotropic hypogonadism. Application of next-generation sequencing has promoted the discovery of novel pathogenic genes in KS pedigrees. Prenatal diagnosis is an effective method in clinical settings to decrease birth defects and block transmission of genetic disorders. However, pregnant women may suffer from physical and psychological distress when fetuses are diagnosed with congenital defects. Preimplantation genetic testing (PGT) is a prospective approach during the in vitro fertilization process that helps to interrupt transmission of hereditary diseases to offspring at an early stage. Thus, genetic testing and counseling are recommended to KS patients with family histories, prenatal diagnosis and PGT are considered to be useful options.