Kallmann syndrome
Encyclopedia
Kallmann syndrome is a genetic disorder
marked by anosmia
and hypogonadism
- the decreased functioning of the glands that produce sex hormones. Abnormalities in various genes may cause a defect in the hypothalamus
, causing a deficiency of gonadotropin-releasing hormone
(GnRH); this in turn causes deficiences in FSH
and
LH
levels. Kallmann syndrome is also called hypothalamic
hypogonadism
, familial hypogonadism with anosmia, and hypogonadotropic hypogonadism, reflecting its disease mechanism.
Kallmann syndrome was described in 1944 by Franz Josef Kallmann
, a German
-American
geneticist
. However, others, such as the Spanish doctor Aureliano Maestre de San Juan in 1856, had noticed a correlation between anosmia
and hypogonadism. The condition has a low prevalence, and is estimated at 1:10,000 males and 1:50,000 females.
The best-known person who has Kallmann syndrome is the jazz vocalist Jimmy Scott
. In 2004, Canadian writer Brian Brett
published a memoir, Uproar's Your Only Music, about growing up with Kallmann syndrome.
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. However, it is not clear how, if at all, these other problems have the same cause as the hypogonadism and anosmia.
Males present with delayed puberty and may have micropenis
(although congenital micropenis is not present in most male KS cases).
Females present with delayed puberty (i.e., primary amenorrhea) and lack of secondary sex characteristic
s, such as breast development
.
A fraction of cases may present with post-pubertal onset, which results in a phenotypically normal penis in men with subsequent testicular atrophy and loss of some secondary sex traits. These men generally present with sexual impairment and low libido. In women, late-onset Kallmann Syndrome can result in secondary amenorrhea. Anosmia
may or may not be present in these individuals.
via the hypophyseal portal system
, where it triggers production and release of gonadotropin
s (LH
and FSH) from the gonadotrope
s. 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.
In Kallmann syndrome, the GnRH neurons do not migrate properly from the olfactory placode to the hypothalamus during development. The olfactory bulbs also fail to form or have hypoplasia, leading to anosmia or hyposmia.
A report published in 2007 by Dr Nelly Pitteloud and Dr Richard Quinton highlights a possible digenic model for Kallmann syndrome and other forms of hypogonadotrophic hypogonadism. The possibility of two separate gene defects working in combination would account for the variation of symptoms seen with people with Kallmann syndrome, even within family groups.
The genetics of Kallmann syndrome and other forms of hypogonadotrophic hypogonadism is still far from clear with around 70% of cases still with an unknown genetic origin.
(HT). Males are administered human chorionic gonadotropin
(hCG) or testosterone
. Females are treated with estrogen
and progestin
s.
There are a range of different methods for the delivery of HRT, especially for men. The short acting monthly injection is now less widely used in favour of the longer lasting injection, Nebido, which can last from 3 to 6 months depending on the individual. Daily application gels and patches are also available as are implants inserted every 6 months.
Tablets are not thought to be effective for the treatment of Kallmann syndrome due to their low bio-availability once processed by the liver, though this can be overcome by using oil filled capsules which allows the testosterone to reach the blood stream in effective doses.
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. Fertility is maintained only during treatment with these hormones. Once fertility treatment stops, it is necessary to revert to the normal hormone-repleacement therapy (HRT) of testosterone for men and estrogen and progestins for women.
The main health risk, for both men and women, of untreated Kallmann Syndrome is osteoporosis
. Therefore, regular bone-density scans (every two years or so) are advisable, even if with HRT. Additional medication specifically for osteoporosis is necessary in some cases.
One recent paper estimated its incidence at 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 called the KAL-2 gene. This is thought to cause about 10% of cases. However, about 70% of KS cases seem to be the result of autosomal dominant genes, though the identity of those genes is not yet known.
Autosomal recessive mutations of the GnRH-receptor gene (4q13.2) have also been reported. 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. There is debate about whether this is in fact Kallmann Syndrome, because 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.
The social stigma of being left behind by the peer group at a vital stage of physical and emotional development can cause lasting damage in some patients. Some with Kallmann Syndrome find it difficult to fit in to social groups and may have trouble forming relationships, both physically and emotionally. This might be more profound in people who receive diagnoses later in life.
There appear to be a range of psychological outcomes for people with KS from relatively mild to chronic in which the whole 'self' is shaped by having the syndrome. In these people their self-image is essentially filtered through the fact that they have KS. Feelings of inadequacy, being worth less than others and anxiety states may result in some patients. The condition appears to affect men psychologically to a greater degree than women, on average.
Personal hygiene can be a major issue for people without a sense of smell in any social situation. People with Kallmann syndrome may not be aware of the impression they give to other people in close contact with them in terms of odours, either from themselves or their clothes.
Gas leaks within the home can be a serious problem and fitting gas detectors within the home is recommended.
Extra care should be taken with spoilage of food and drink, extra care should be taken with the expiration dates.
With the key symptom being not going through puberty at the normal age it can produce a huge effect on a person’s social development as well as physical development.
It will vary from person to person but in general men with Kallmann syndrome will have a smaller penile length than the average for the population, which in addition to the lack of testicular development can affect self confidence to such a degree that sexual activity is not even attempted. Most men with Kallmann syndrome can have a normal, active sex life but the confidence required to achieve this is sometimes beyond some men with Kallmann syndrome and they have less sexual activity than other people the same age.
Another aspect of Kallmann syndrome is the social isolation. Since it is such a rare condition a lot of patients with Kallmann syndrome have never even met or talked to a fellow patient. The ability to meet and talk to other people with the condition goes a long way to helping a patient come to terms with the condition.
The treatment of patients with Kallmann syndrome is fairly straightforward once diagnosed with the use of hormone replacement therapies and fertility injections in some cases. The bigger issue is the initial diagnosis, especially in the crucial teenage years. The patients that cope better with Kallmann syndrome on the whole are those that are diagnosed before the age of 16 and have prompt treatment. Problems can arise if people are told to “wait and see” too long into their teenage years instead of being referred for specialist endocrinologist review where a case of pubertal delay can be separated from a case of Kallmann syndrome.
Outwardly there is nothing striking about a person with Kallmann syndrome. They will not look any different from anybody else, and come in all different shapes and sizes. Once treatment is started and normal hormone levels are restored there are no side effects or life expectancy issues associated with having Kallmann syndrome. The lack of sense of smell might be noticed by people, but this can easily be explained away without going into a full description of Kallmann syndrome.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
marked by anosmia
Anosmia
Anosmia is a lack of functioning olfaction, or in other words, an inability to perceive odors. Anosmia may be either temporary or permanent. A related term, hyposmia, refers to a decreased ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one...
and hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
- the decreased functioning of the glands that produce sex hormones. Abnormalities in various genes may cause a defect in the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, causing a deficiency of gonadotropin-releasing hormone
Gonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
(GnRH); this in turn causes deficiences in FSH
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
and
LH
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
levels. Kallmann syndrome is also called hypothalamic
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
, familial hypogonadism with anosmia, and hypogonadotropic hypogonadism, reflecting its disease mechanism.
Kallmann syndrome was described in 1944 by Franz Josef Kallmann
Franz Josef Kallmann
Franz Josef Kallmann MD , a German-born American psychiatrist, was one of the pioneers in the study of the genetic basis of psychiatric disorders...
, a German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
-American
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
geneticist
Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
. However, others, such as the Spanish doctor Aureliano Maestre de San Juan in 1856, had noticed a correlation between anosmia
Anosmia
Anosmia is a lack of functioning olfaction, or in other words, an inability to perceive odors. Anosmia may be either temporary or permanent. A related term, hyposmia, refers to a decreased ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one...
and hypogonadism. The condition has a low prevalence, and is estimated at 1:10,000 males and 1:50,000 females.
The best-known person who has Kallmann syndrome is the jazz vocalist Jimmy Scott
Jimmy Scott
Jimmy Scott , aka "Little" Jimmy Scott, is an American jazz vocalist famous for his unusually high contralto voice which is due to Kallmann's syndrome, a very rare genetic condition. The condition stunted his growth at four feet eleven inches until, at age 37, he grew another 8 inches to the...
. In 2004, Canadian writer Brian Brett
Brian Brett
Brian Brett is a Canadian poet and novelist.He studied literature at Simon Fraser University from 1969 to 1974...
published a memoir, Uproar's Your Only Music, about growing up with Kallmann syndrome.
Features
Kallmann syndrome's characteristics:- Hypogonadotropic hypogonadism (a lack of the pituitary hormonesPituitary glandIn vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
LHLuteinizing hormoneLuteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
and FSHFSHFSH may refer to:* Follicle-stimulating hormone* Fox Sports Houston, a regional Fox Sports Net affiliate station for the Houston, Texas area* Facioscapulohumeral muscular dystrophy* International Civil Aviation Organisation code for Flash Airlines...
) - Congenital (present from birth) anosmiaAnosmiaAnosmia is a lack of functioning olfaction, or in other words, an inability to perceive odors. Anosmia may be either temporary or permanent. A related term, hyposmia, refers to a decreased ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one...
(complete inability to smell) or hyposmia (decreased ability to smell) - Normal stature
It can occasionally be associated with optic problems, such as colour blindness or optic atrophy, nerve deafness, cleft palate, cryptorchidism
Cryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
, renal agenesis
Renal agenesis
Renal agenesis is a unilateral or bilateral medical condition in which one or both fetal kidneys fail to develop leading to oligohydramnios, resulting in a 40-fold increase in perinatal mortality.It can be associated with RET or UPK3A.-Bilateral:...
, and mirror movement disorder. However, it is not clear how, if at all, these other problems have the same cause as the hypogonadism and anosmia.
Males present with delayed puberty and may have micropenis
Micropenis
Micropenis is an unusually small penis. A common criterion is a dorsal erect penile length of at least 2.5 standard deviations smaller than the mean human penis size. The condition is usually recognized shortly after birth...
(although congenital micropenis is not present in most male KS cases).
Females present with delayed puberty (i.e., primary amenorrhea) and lack of secondary sex characteristic
Secondary sex characteristic
Secondary sex characteristics are features that distinguish the two sexes of a species, but that are not directly part of the reproductive system. They are believed to be the product of sexual selection for traits which give an individual an advantage over its rivals in courtship and aggressive...
s, such as breast development
Thelarche
Thelarche is the onset of secondary breast development, usually occurring at the beginning of puberty in girls. Its etymology is from Greek θηλή [tʰelḗ], “nipple” and ἀρχή [arkʰḗ], “beginning, onset”. Thelarche is usually noticed as a firm, tender lump directly under the centre of the nipple...
.
A fraction of cases may present with post-pubertal onset, which results in a phenotypically normal penis in men with subsequent testicular atrophy and loss of some secondary sex traits. These men generally present with sexual impairment and low libido. In women, late-onset Kallmann Syndrome can result in secondary amenorrhea. Anosmia
Anosmia
Anosmia is a lack of functioning olfaction, or in other words, an inability to perceive odors. Anosmia may be either temporary or permanent. A related term, hyposmia, refers to a decreased ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one...
may or may not be present in these individuals.
Diagnosis
The diagnosis is often one of exclusion found during the workup of delayed puberty. The presence of anosmia with delayed puberty should suggest Kallmann syndrome.Pathophysiology
Under normal conditions, GnRH travels from the hypothalamus to the pituitary glandPituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
via the hypophyseal portal system
Hypophyseal portal system
The hypophyseal portal system is the system of blood vessels that link the hypothalamus and the anterior pituitary in the brain.It allows endocrine communication between the two structures. It is part of the hypothalamic-pituitary-adrenal axis. The anterior pituitary receives releasing and...
, where it triggers production and release of gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
s (LH
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
and FSH) from the gonadotrope
Gonadotrope
Gonadotropes are endocrine cells in the anterior pituitary that produce the gonadotropins, follicle-stimulating hormone and luteinizing hormone...
s. When GnRH is low, the pituitary does not create the normal amount of gonadotropins. The gonadotropins normally increase the production of gonadal steroids
Sex steroid
Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and...
; so, when they are low, these steroids will be low as well.
In Kallmann syndrome, the GnRH neurons do not migrate properly from the olfactory placode to the hypothalamus during development. The olfactory bulbs also fail to form or have hypoplasia, leading to anosmia or hyposmia.
| OMIM | Name | Gene | Locus Locus (genetics) In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map... |
Description |
|---|---|---|---|---|
| KAL1 | KAL1 | Xp22.3 | Kallmann syndrome can be inherited as an X-linked recessive trait, in which case there is a defect in the KAL1 KAL1 gene The KAL1 gene is a human gene which is located on the X chromosome at Xp22.3 and is affected in some individuals with Kallmann syndrome. This gene codes for a protein named anosmin-1, which is responsible for migration of certain nerve cell precursors during embryogenesis... gene, which maps to chromosome Xp22.3. KAL encodes a neural cell adhesion molecule, anosmin-1 Anosmin-1 Anosmin-1 is a secreted, EM associated glycoprotein found in humans and other organisms responsible for normal development, which is expressed in the brain, spinal cord and kidney. Absence or damage to the protein results in Kallmann syndrome in humans, which is characterized by loss of olfactory... . Anosmin-1 is normally expressed in the brain Brain The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,... , facial Face The face is a central sense organ complex, for those animals that have one, normally on the ventral surface of the head, and can, depending on the definition in the human case, include the hair, forehead, eyebrow, eyelashes, eyes, nose, ears, cheeks, mouth, lips, philtrum, temple, teeth, skin, and... mesenchyme Mesenchyme Mesenchyme, or mesenchymal connective tissue, is a type of undifferentiated loose connective tissue that is derived mostly from mesoderm, although some are derived from other germ layers; e.g. some mesenchyme is derived from neural crest cells and thus originates from the ectoderm... , mesonephros Mesonephros The mesonephros is one of three excretory organs that develop in vertebrates. It serves as the main excretory organ of aquatic vertebrates and as a temporary kidney in reptiles, birds, and mammals. The mesonephros is included in the Wolffian body after Caspar Friedrich Wolff who described it in 1759... and metanephros. It is required to promote migration of GnRH neurons into the hypothalamus Hypothalamus The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions... . It also allows migration of olfactory neurons from the olfactory bulbs to the hypothalamus. |
|
| KAL2 | FGFR1 | 8p11.2-p11.1 | 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. | |
| KAL3 | PROKR2 | 20p13 | An additional autosomal cause of Kallmann syndrome has been reported by 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. |
A report published in 2007 by Dr Nelly Pitteloud and Dr Richard Quinton highlights a possible digenic model for Kallmann syndrome and other forms of hypogonadotrophic hypogonadism. The possibility of two separate gene defects working in combination would account for the variation of symptoms seen with people with Kallmann syndrome, even within family groups.
The genetics of Kallmann syndrome and other forms of hypogonadotrophic hypogonadism is still far from clear with around 70% of cases still with an unknown genetic origin.
Treatment
Treatment is directed at restoring the deficient hormones—hormone therapyHormone therapy
Hormone therapy, or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also referred to as hormonal therapy...
(HT). Males are administered human chorionic gonadotropin
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
(hCG) or testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
. Females are treated with estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
and progestin
Progestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
s.
There are a range of different methods for the delivery of HRT, especially for men. The short acting monthly injection is now less widely used in favour of the longer lasting injection, Nebido, which can last from 3 to 6 months depending on the individual. Daily application gels and patches are also available as are implants inserted every 6 months.
Tablets are not thought to be effective for the treatment of Kallmann syndrome due to their low bio-availability once processed by the liver, though this can be overcome by using oil filled capsules which allows the testosterone to reach the blood stream in effective doses.
To induce fertility in males or females, GnRH (aka LHRH) is administered by an infusion pump
Infusion pump
An infusion pump infuses fluids, medication or nutrients into a patient's circulatory system. It is generally used intravenously, although subcutaneous, arterial and epidural infusions are occasionally used....
, or hCG/hMG/FSH/LH combinations are administered through regular injections. Fertility is maintained only during treatment with these hormones. Once fertility treatment stops, it is necessary to revert to the normal hormone-repleacement therapy (HRT) of testosterone for men and estrogen and progestins for women.
The main health risk, for both men and women, of untreated Kallmann Syndrome is osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
. Therefore, regular bone-density scans (every two years or so) are advisable, even if 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 estimated its incidence at 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 called the KAL-2 gene. This is thought to cause about 10% of cases. However, about 70% of KS cases seem to be the result of autosomal dominant genes, though the identity of those genes is not yet known.
Autosomal recessive mutations of the GnRH-receptor gene (4q13.2) have also been reported. 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. There is debate about whether this is in fact Kallmann Syndrome, because 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.
Psychology
In some cases, the psychological effects of having this condition can outweigh the significance of any physical symptoms.The social stigma of being left behind by the peer group at a vital stage of physical and emotional development can cause lasting damage in some patients. Some with Kallmann Syndrome find it difficult to fit in to social groups and may have trouble forming relationships, both physically and emotionally. This might be more profound in people who receive diagnoses later in life.
There appear to be a range of psychological outcomes for people with KS from relatively mild to chronic in which the whole 'self' is shaped by having the syndrome. In these people their self-image is essentially filtered through the fact that they have KS. Feelings of inadequacy, being worth less than others and anxiety states may result in some patients. The condition appears to affect men psychologically to a greater degree than women, on average.
Practical Issues
While the lack of sense of smell may not be important when compared to the lack of sexual development, it does give rise to some situations in which care should be taken.Personal hygiene can be a major issue for people without a sense of smell in any social situation. People with Kallmann syndrome may not be aware of the impression they give to other people in close contact with them in terms of odours, either from themselves or their clothes.
Gas leaks within the home can be a serious problem and fitting gas detectors within the home is recommended.
Extra care should be taken with spoilage of food and drink, extra care should be taken with the expiration dates.
A patient’s perspective
Having Kallmann syndrome can have a profound effect on a person’s life, however it will affect different people in different ways. Age of diagnosis and treatment is a big key to how well an individual patient copes with the condition. For some patients the ability to put a name to the condition and the knowledge that they are not the only person in the world with this condition is very reassuring.With the key symptom being not going through puberty at the normal age it can produce a huge effect on a person’s social development as well as physical development.
It will vary from person to person but in general men with Kallmann syndrome will have a smaller penile length than the average for the population, which in addition to the lack of testicular development can affect self confidence to such a degree that sexual activity is not even attempted. Most men with Kallmann syndrome can have a normal, active sex life but the confidence required to achieve this is sometimes beyond some men with Kallmann syndrome and they have less sexual activity than other people the same age.
Another aspect of Kallmann syndrome is the social isolation. Since it is such a rare condition a lot of patients with Kallmann syndrome have never even met or talked to a fellow patient. The ability to meet and talk to other people with the condition goes a long way to helping a patient come to terms with the condition.
The treatment of patients with Kallmann syndrome is fairly straightforward once diagnosed with the use of hormone replacement therapies and fertility injections in some cases. The bigger issue is the initial diagnosis, especially in the crucial teenage years. The patients that cope better with Kallmann syndrome on the whole are those that are diagnosed before the age of 16 and have prompt treatment. Problems can arise if people are told to “wait and see” too long into their teenage years instead of being referred for specialist endocrinologist review where a case of pubertal delay can be separated from a case of Kallmann syndrome.
Outwardly there is nothing striking about a person with Kallmann syndrome. They will not look any different from anybody else, and come in all different shapes and sizes. Once treatment is started and normal hormone levels are restored there are no side effects or life expectancy issues associated with having Kallmann syndrome. The lack of sense of smell might be noticed by people, but this can easily be explained away without going into a full description of Kallmann syndrome.
External links
- GeneReviews/NCBI/NIH/UW entry on Kallmann syndrome
- Updated information web site on Kallmann syndrome
- 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)