| Kallmann syndrome Classification and external resources |
|
 |
|
|---|---|
| The structure of GNRH1 (from PDB 1YY1) |
|
| ICD-10 | E23.0 |
| ICD-9 | 253.4 |
| OMIM | 308700 147950 244200 138850 607002 |
| DiseasesDB | 7091 |
| eMedicine | med/1216 med/1342 |
| MeSH | D017436 |
Kallmann syndrome is an example of hypogonadism (decreased functioning of the sex hormone-producing glands) caused by a deficiency of gonadotropin-releasing hormone (GnRH), which is created by the hypothalamus. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings E00-E35 - Endocrine diseases (E00-E07 Thyroid gland / Thyroid hormone ( Congenital iodine-deficiency syndrome ( The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Hypogonadism is a medical term for a defect of the Reproductive system that results in lack of function of the Gonads ( ovaries or testes) Gonadotropin-releasing hormone ( GNRH) also known as Luteinizing-hormone releasing hormone ( LHRH) is a tropic Peptide Hormone The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis Kallmann syndrome is also known as hypothalamic hypogonadism, familial hypogonadism with anosmia, or hypogonadotropic hypogonadism, reflecting its disease mechanism. The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis Hypogonadism is a medical term for a defect of the Reproductive system that results in lack of function of the Gonads ( ovaries or testes) Anosmia is the lack of Olfaction, or an absence of the ability to smell Hypogonadism is a medical term for a defect of the Reproductive system that results in lack of function of the Gonads ( ovaries or testes)
Kallmann syndrome is a form of tertiary hypogonadism reflecting the fact the primary cause of the defect in sex hormone production lies within the pituitary and hypothalamus rather than a physical defect of the testes or ovaries themselves.
Kallmann syndrome was described in 1944 by Franz Josef Kallmann, a German-American geneticist. Year 1944 ( MCMXLIV) was a Leap year starting on Saturday (link will display full calendar of the Gregorian calendar. Franz Josef Kallmann MD ( July 24, 1897 Neumarkt, Silesia &ndash May 12, 1965 New York) a German-born American Germany, officially the Federal Republic of Germany ( ˈbʊndəsʁepuˌbliːk ˈdɔʏtʃlant is a Country in Central Europe. The United States of America —commonly referred to as the A geneticist is a scientist who studies Genetics, the science of Heredity and variation of Organisms A geneticist can be employed as a researcher [1][2] However, others - such as the Spanish doctor Aureliano Maestre de San Juan - had noticed a correlation between anosmia and hypogonadism in 1856.
The most well known person who has Kallmann syndrome in modern times is the jazz vocalist Jimmy Scott. Jimmy Scott ( July 17, 1925 in Cleveland) aka "Little" Jimmy Scott, is an American Jazz Vocalist. In 2004, Canadian writer Brian Brett published a memoir, Uproar's Your Only Music, about growing up with Kallmann syndrome. Brian Brett (born 28 April 1950) is a Canadian Poet and Novelist.
Contents |
Features
Kallmann syndrome is characterized by:
- Hypogonadotropic hypogonadism (a lack of the pituitary hormones LH and FSH)
- Congenital (present from birth) anosmia (complete inability to smell) or hyposmia (decreased ability to smell)
It can occasionally be associated with optic problems, such as colour blindness or optic atrophy, nerve deafness, cleft palate, cryptorchidism, renal agenesis, and mirror movement disorder. Hypogonadism is a medical term for a defect of the Reproductive system that results in lack of function of the Gonads ( ovaries or testes) The pituitary gland, or hypophysis, is an Endocrine gland about the size of a Pea. Luteinizing hormone ( LH, also known as lutropin) is a Hormone produced by the Anterior pituitary gland. Anosmia is the lack of Olfaction, or an absence of the ability to smell Color blindness, a Color vision deficiency is the inability to perceive differences between some of the Colors that others can distinguish Cleft lip (cheiloschisis and cleft palate (palatoschisis which can also occur together as cleft lip and palate are variations of a type of clefting Congenital Cryptorchidism is the absence of one or both Testes from the Scrotum. The absence of one (unilateral or both (bilateral Kidneys at birth However, it is not clear at this time how or if these other problems have the same cause as the hypogonadism and anosmia. These problems are more often present in those without Kallmann syndrome.
Males present with delayed puberty and may have micropenis (although congenital micropenis is not present in the majority of male KS cases). Micropenis is a medical term that describes an unusually small Penis.
Females present with delayed puberty (i. e. primary amenorrhea) and lack of secondary sex characteristics, such as breast development. Amenorrhoea ( BE) amenorrhea ( AmE) or amenorrhœa, is the absence of a Menstrual period in a woman of reproductive age Secondary sex characteristics are traits that distinguish the two Sexes of a species but that are not directly part of the Reproductive system. Thelarche is the first stage of secondary (postnatal Breast development usually occurring at the beginning of Puberty in girls
Diagnosis
The diagnosis is often one of exclusion found during the workup of delayed puberty. The presence of anosmia together with micropenis in boys should suggest Kallmann syndrome (although micropenis alone may have other causes). Micropenis is a medical term that describes an unusually small Penis.
Pathophysiology
Under normal conditions, GnRH travels from the hypothalamus to the pituitary gland via the hypophyseal portal system, where it triggers production and release of gonadotropins (LH and FSH) from the gonadotropes. The pituitary gland, or hypophysis, is an Endocrine gland about the size of a Pea. The hypophyseal portal system (or hypothalamo-hypophyseal portal system) is the system of Blood vessels that links the Hypothalamus and the Anterior Gonadotropins are Protein Hormones secreted by Gonadotrope cells of the Pituitary gland of Vertebrates Gonadotropin is sometimes Luteinizing hormone ( LH, also known as lutropin) is a Hormone produced by the Anterior pituitary gland. Follicle-stimulating hormone ( FSH) is a Hormone synthesized and secreted by Gonadotropes in the Anterior pituitary gland. Gonadotropes are basophilic cells in the Anterior pituitary which produce the Gonadotropins Follicle-stimulating hormone (FSH and When GnRH is low, the pituitary does not create the normal amount of gonadotropins. The gonadotropins normally increase the production of gonadal steroids, so when they are low, these steroids will be low as well. Sex steroids, also known as gonadal steroids, are Steroid hormones that interact with Vertebrate Androgen or Estrogen receptors
In Kallmann syndrome, the GnRH neurons do not migrate properly from the olfactory placode to the hypothalamus during development. A placode is an area of thickening in the embryonic Epithelial layer where some organ or structure later develops The olfactory bulbs also fail to form or have hypoplasia, leading to anosmia or hyposmia.
Kallmann syndrome can be inherited as an X-linked recessive trait, in which case there is a defect in the KAL1 gene, which maps to chromosome Xp22. The KAL1 gene is a human Gene which is located on the X chromosome at Xp22 3. [3] KAL encodes a neural cell adhesion molecule, anosmin-1. Anosmin-1 is a Protein found in Humans and other Organisms which is responsible for normal development. Anosmin-1 is normally expressed in the brain, facial mesenchyme, mesonephros and metanephros. The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain The term face refers to the central sense organ complex for those animals that have one normally on the ventral surface of the head and can depending on the definition Mesenchyme refers to loosely organized connective tissue present in the embryo regardless of origin The mesonephros ( Latin for "middle Kidney " is one of three excretory organs that develop in Vertebrates It serves as the main excretory The kidneys are complicated organs that have numerous biological roles It is required to promote migration of GnRH neurons into the hypothalamus. Gonadotropin-releasing hormone ( GNRH) also known as Luteinizing-hormone releasing hormone ( LHRH) is a tropic Peptide Hormone The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis It also allows migration of olfactory neurons from the olfactory bulbs to the hypothalamus. The olfactory bulb is a structure of the Vertebrate Forebrain involved in Olfaction, the perception of Odors.
An autosomal dominant gene on chromosome 8 {8p12} (KAL-2 or FGFR-1 (fibroblast growth factor receptor 1)) is thought to cause about 10% of cases. There is some recent evidence to suggest a degree of linkage between the KAL-1 and FGFR-1 genes.
An additional autosomal cause of Kallmann syndrome has been reported[4] by a mutations in the prokineticin receptor-2 gene (PROKR2)(KAL-3) at position 20p13 and its ligand prokineticin 2 (PROK2)(KAL-4) at position 3p21. 1. It was noted that mutations in these genes brought about various degrees of olfactory and reproductive dysfunction, but not the other symptoms seen in KAL-1 and KAL-2 forms of Kallmann Syndrome. The authors of the paper suggested that up to 30% of all Kallmann Syndrome cases can be linked to known genetic mutations.
Treatment
Treatment is directed at restoring the deficient hormones -- known as hormone therapy (HT). Hormone therapy, or hormonal therapy is the use of Hormones in medical treatment Males are administered human chorionic gonadotropin (hCG) or testosterone. Human chorionic gonadotropin ( hCG) is a Glycoprotein Hormone produced in Pregnancy that is made by the Embryo soon after conception Testosterone is a Steroid hormone from the Androgen group In mammals testosterone is primarily secreted in the testes of males and the Ovaries Females are treated with oestrogen and progestins. Estrogens (US otherwise oestrogens or œstrogens) are a group of Steroid compounds named for their importance in the Estrous cycle, A progestin is a synthetic progestagen that has progestinic effects similar to Progesterone.
To induce fertility in males or females, GnRH (aka LHRH) is administered by an infusion pump, or hCG/hMG/FSH/LH combinations are administered through regular injections. An infusion pump infuses fluids Medication or Nutrients into a patient's Circulatory system. Fertility is only maintained whilst actually being treated with these hormones. Once fertility treatment stops it is necessary to revert to the normal HRT of testosterone for men and oestrogen + progestins for women.
The main health risk, for both men and women, of untreated Kallmann Syndrome is osteoporosis. Osteoporosis is a Disease of Bone that leads to an increased risk of fracture. Therefore, regular bone density scans (every 2 years or so) are advisable, even if being treated with HRT. Additional medication specifically for osteoporosis is necessary in some cases.
Epidemiology
Kallmann syndrome occurs at a rate of 1 in 10,000 male births and 1 in 50,000 female births. It may be inherited as an X-linked condition, an autosomal dominant condition or as an autosomal recessive condition. Statistics are sparse, but it seems that autosomal dominant is the most common form of heredity.
One recent paper [5] quoted an incidence in males of 0. 025%, or 1 in 4,000, with the female incidence being 3 to 5 times less.
Even though mutations in the KAL-1 gene on the X chromosome can cause Kallmann syndrome, only 11-14% of patients with Kallmann syndrome have detectable KAL-1 mutations.
Autosomal dominant mutations have been described with the FGFR-1 (8p12) gene, sometimes referred to as the KAL-2 gene. This is thought to cause about 10% of cases. However, the majority of KS cases (70%) would seem to be the result of autosomal dominant genes even though the identity of those genes is not yet known.
Autosomal recessive mutations of the GnRH receptor gene (4q13. 2) have also been reported. [5] This defect appears to produce a wider spectrum of physical symptoms than with the other gene defects, and the defect lies in the ability of the pituitary gland to recognize GnRH, rather than the ability of the hypothalamus to produce GnRH. It is debatable as to whether this is in fact Kallmann syndrome since the GnRH receptor development is not related to anosmia.
There may also be no obvious family history of inheritance (sporadic cases). However, it is possible for Kallmann syndrome genes to be passed on to children of a sporadic case.
References
- ^ Kallmann FJ, Schönfeld WA, Barrera SE. The genetic aspects of primary eunuchoidism. Am J Ment Defic 1943-1944;48:203-236.
- ^ synd/2549 at Who Named It
- ^ MacColl G, Bouloux P, Quinton R (2002). Who Named It? is an English-language dictionary of medical eponyms and the People associated with their identification "Kallmann syndrome: adhesion, afferents, and anosmia". Neuron 34 (5): 675-8. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12062015.
- ^ Dode C, et al. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet. 2: e175, 2006.
- ^ a b Quinton R. Topical Endocrinology 22. (15-20)
External links
- Information web site on Kallmann's syndrome
- Man, 33, seeks puberty The case of Lawrence Koomson a physician who was treated for the condition as filmed in the documentary. (BBC)
Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic