Dataset Information

Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future.

ABSTRACT: The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are genetic disorders that are rooted in a GnRH deficiency but often accompanied by a variety of non-reproductive phenotypes such as the loss of the sense of smell and defects of the skeleton, eye, ear, kidney, and heart. Recent progress in DNA sequencing technology has produced a wealth of information regarding the genetic makeup of CHH and KS patients and revealed the resilient yet complex nature of the human reproductive neuroendocrine system. Further research on the molecular basis of the disease and the diverse signal pathways involved will aid in improving the diagnosis, treatment, and management of CHH and KS patients as well as in developing more precise genetic screening and counseling regime.

SUBMITTER: Kim SH

PROVIDER: S-EPMC4722398 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future.

Kim Soo Hyun SH

Endocrinology and metabolism (Seoul, Korea) 20151201 4

The proper development and coordination of the hypothalamic-pituitary-gonadal (HPG) axis are essential for normal reproductive competence. The key factor that regulates the function of the HPG axis is gonadotrophin-releasing hormone (GnRH). Timely release of GnRH is critical for the onset of puberty and subsequent sexual maturation. Misregulation in this system can result in delayed or absent puberty and infertility. Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are g ...[more]

PMID: 26790381

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Project description:Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency (IGD) IGD is a genetically and clinically heterogeneous disorder. Mutations in many different genes are able to explain ~40% of the causes of IGD, with the rest of cases remaining genetically uncharacterized. While most mutations are inherited in X-linked, autosomal dominant, or autosomal recessive pattern, several IGD genes are shown to interact with each other in an oligogenic manner. In addition, while the genes involved in the pathogenesis of IGD act on either neurodevelopmental or neuroendocrine pathways, a subset of genes are involved in both pathways, acting as "overlap genes". Thus, some IGD genes play the role of the modifier genes or "second hits", providing an explanation for incomplete penetrance and variable expressivity associated with some IGD mutations. The clinical spectrum of IGD includes a variety of disorders including Kallmann Syndrome (KS), i.e. hypogonadotropic hypogonadism with anosmia, and its normosmic variation normosmic idiopathic hypogonadotropic hypogonadism (nIHH), which represent the most severe aspects of the disorder. Apart from these disorders, there are also "milder" and more common reproductive diseases associated with IGD, including hypothalamic amenorrhea (HA), constitutional delay of puberty (CDP) and adult-onset hypogonadotropic hypogonadism (AHH). Interestingly, neurodeveloplmental genes are associated with the KS form of IGD, due to the topographical link between the GnRH neurons and the olfactory placode. On the other hand, neuroendocrine genes are mostly linked to nIHH. However, a great deal of clinical and genetic overlap characterizes the spectrum of the IGD disorders. IGD is also characterized by a wide variety of non-reproductive features, including midline facial defects such as cleft lip and/or palate, renal agenesis, short metacarpals and other bone abnormalities, hearing loss, synkinesia, eye movement abnormalities, poor balance due to cerebellar ataxia, etc. Therefore, genetic screening should be offered in patients with IGD, as it can provide valuable information for genetic counseling and further understanding of IGD.

Dataset Information

Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future.

Publications

Congenital Hypogonadotropic Hypogonadism and Kallmann Syndrome: Past, Present, and Future.

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