Kallmann syndrome

Sexual and Reproductive Health

Clinicals - History

Fact Explanation
Delayed or absent puberty GnRH pulsatile secretions that occur at adolescence initiate the hormonal changes of puberty which are followed by development of secondary sexual characteristics of both sexes and menstruation in females. Patients with Kallmann syndrome (KS) have GnRH deficiency so their onset of puberty is either delayed or absent. Delayed or absent puberty
GnRH pulsatile secretions that occur at adolescence initiate the hormonal changes of puberty which are followed by development of secondary sexual characteristics of both sexes and menstruation in females. Patients with Kallmann syndrome (KS) have GnRH deficiency so their onset of puberty is either delayed or absent.
Impaired/abset sense of smell Occurs due to absent (aplasia) or poorly developed (hypoplasia) olfactory bulbs and tracts. Impaired/abset sense of smell
Occurs due to absent (aplasia) or poorly developed (hypoplasia) olfactory bulbs and tracts.
Primary amenorrhoea Results from the lack of gonadotrophins which are necessary to initiate and mantain the normal menstrual cycle. Primary amenorrhoea
Results from the lack of gonadotrophins which are necessary to initiate and mantain the normal menstrual cycle.
Small testis in males Occurs as a result of the congenital GnRH deficiency seen in KS Small testis in males
Occurs as a result of the congenital GnRH deficiency seen in KS
Undescended testes in males Occurs as a result of the congenital GnRH deficiency seen in KS Undescended testes in males
Occurs as a result of the congenital GnRH deficiency seen in KS
Lack of breast development in females Due to the low estradiol levels in females with KS. Lack of breast development in females
Due to the low estradiol levels in females with KS.
Hearing difficulties Sensorineural hearing loss is seen mainly with patients having the X-linked form of KSThe underlying defect is believed to occur during the organogenesis period of the embryo. Hearing difficulties
Sensorineural hearing loss is seen mainly with patients having the X-linked form of KSThe underlying defect is believed to occur during the organogenesis period of the embryo.
Cleft lip or cleft palate Occur in some patients with KS, particularly those with KAL2 gene defect. Cleft lip or cleft palate
Occur in some patients with KS, particularly those with KAL2 gene defect.
Abnormalities of teeth Is seen in some patients with KS. Which may have resulted from abnomalities that occur during embryonic development Abnormalities of teeth
Is seen in some patients with KS. Which may have resulted from abnomalities that occur during embryonic development
Lack of facial hair growth in males Occurs due to low level of testosterone which determines secondary sexual characteristcs development in males Lack of facial hair growth in males
Occurs due to low level of testosterone which determines secondary sexual characteristcs development in males
Difficulty in doing tasks that require the hands to move separately (eg;- playing a musical instrument) Some patients with KS bimanual synkinesis, in which the movements of one hand are mirrored by the other hand so that it is difficult to do tasks that require hands to move separately. Difficulty in doing tasks that require the hands to move separately (eg;- playing a musical instrument)
Some patients with KS bimanual synkinesis, in which the movements of one hand are mirrored by the other hand so that it is difficult to do tasks that require hands to move separately.
Dyspareunia Due to lack of vaginal lubrication due to estrogen deficiency Dyspareunia
Due to lack of vaginal lubrication due to estrogen deficiency
Subfertility Spermatogenesis in mals and ovulation in females is impaired due to deficient secretion of hormones in the hypothalamo-pituitary-gonadal axis, when they have KS Subfertility
Spermatogenesis in mals and ovulation in females is impaired due to deficient secretion of hormones in the hypothalamo-pituitary-gonadal axis, when they have KS
Loss of libido Occurs due to low levels of testosterone Loss of libido
Occurs due to low levels of testosterone
Erectile Dysfunction Seen in some men with KS Erectile Dysfunction
Seen in some men with KS

Clinicals - Examination

Fact Explanation
Reduced/ absent sense of smell Patients with KS have absent (aplasia) or poorly developed (hypoplasia) olfactory bulbs and tracts. Reduced/ absent sense of smell
Patients with KS have absent (aplasia) or poorly developed (hypoplasia) olfactory bulbs and tracts.
Eunuchoid body habitus (i.e., arm span exceeds height by ≥5 cm) Sex hormones are needed for the fusion of growth plates in bones. Due to the absence of sex hormones the growth plates fail to fuse resulting in a eunuchoid body habitus Eunuchoid body habitus (i.e., arm span exceeds height by ≥5 cm)
Sex hormones are needed for the fusion of growth plates in bones. Due to the absence of sex hormones the growth plates fail to fuse resulting in a eunuchoid body habitus
Undescended testes (cryptorchidism) in males Occurs due to congenital GnRH deficiency Undescended testes (cryptorchidism) in males
Occurs due to congenital GnRH deficiency
Small penis (microphallus) in males Also occurs due tocongenital GnRH deficiency Small penis (microphallus) in males
Also occurs due tocongenital GnRH deficiency
Absent facial hair and decreased body hair in men Due to low plasma testosterone levels, secondary sexual characteristics development is deficient Absent facial hair and decreased body hair in men
Due to low plasma testosterone levels, secondary sexual characteristics development is deficient
Absent deepening of voice in males Tetosterone deficiency seen in KS affects development of secondary sexual characteristics Absent deepening of voice in males
Tetosterone deficiency seen in KS affects development of secondary sexual characteristics
Prepubertal testicular volume (i.e., <4 mL)is seen in males Results from gonadotrophin deficiency. Men with KS typically have Tanner stage I-II genitalia. Prepubertal testicular volume (i.e., <4 mL)is seen in males
Results from gonadotrophin deficiency. Men with KS typically have Tanner stage I-II genitalia.
Prepuberta breast size present in females Females with KS typically have Tanner stage I breast development due to deficiency of estradiol Prepuberta breast size present in females
Females with KS typically have Tanner stage I breast development due to deficiency of estradiol
Unilateral absent kidney May result from the developmental failures that occur during the organogenesis period of the embryo. Unilateral absent kidney
May result from the developmental failures that occur during the organogenesis period of the embryo.
cleft lip with or without a cleft palate Occur in some patients with KS, particularly those with KAL2 gene defect. cleft lip with or without a cleft palate
Occur in some patients with KS, particularly those with KAL2 gene defect.
Abnormal eye movements Is seenin some patients with KS Abnormal eye movements
Is seenin some patients with KS
Abnormalities in teeth Is seen in some patients with KS. Which may have resulted from abnomalities that occur during embryonic development Abnormalities in teeth
Is seen in some patients with KS. Which may have resulted from abnomalities that occur during embryonic development
Impaired hearing Sensorineural hearing loss is seen mainly with patients having the X-linked form of KSThe underlying defect is believed to occur during the organogenesis period of the embryo. Impaired hearing
Sensorineural hearing loss is seen mainly with patients having the X-linked form of KSThe underlying defect is believed to occur during the organogenesis period of the embryo.
Bimanual synkinesis Mirror movements of hands or bimanual synkinesis seen in KS is attributed to an abnormal projection of the corticospinal tract Bimanual synkinesis
Mirror movements of hands or bimanual synkinesis seen in KS is attributed to an abnormal projection of the corticospinal tract
High arched palate A fetal developmental abnormality seen in KS patients with genetic mutations such as KAL1,CHD7 High arched palate
A fetal developmental abnormality seen in KS patients with genetic mutations such as KAL1,CHD7

Investigations - Diagnosis

Fact Explanation
Urine beta-human chorionic gonadotropin To exclude pregnancy in females wtih amenorrhoea Urine beta-human chorionic gonadotropin
To exclude pregnancy in females wtih amenorrhoea
Serum ferritin To exclude hereditary haemochromatosis Serum ferritin
To exclude hereditary haemochromatosis
Serum total testosterone Total testosterone level <100 ng/dl is seen among males with KS Serum total testosterone
Total testosterone level <100 ng/dl is seen among males with KS
Serum estradiol Estradiol level <20 pg/dl is seen among adult females with KS Serum estradiol
Estradiol level <20 pg/dl is seen among adult females with KS
Serum luteinizing hormone(LH) Low basal level of LH is present in both males and females with KS Serum luteinizing hormone(LH)
Low basal level of LH is present in both males and females with KS
Serum follicle-stimulating hormone(FSH) Low basal level of FSH is present in both males and females with KS Serum follicle-stimulating hormone(FSH)
Low basal level of FSH is present in both males and females with KS
Serum prolactin Proactin levels are normal in patients with Kallmann syndrome. This test is done to exclude hyperprolactinemic conditions that can cause hypogonadism Serum prolactin
Proactin levels are normal in patients with Kallmann syndrome. This test is done to exclude hyperprolactinemic conditions that can cause hypogonadism
Magnetic resonance imaging(MRI) of the brain To show the hypoplasia or aplasia of the olfactory bulbs and tracts. MRI is also useful to exclude hypothalamic or pituitary lesions as the cause of hypogonadotrophic hypogonadism. Magnetic resonance imaging(MRI) of the brain
To show the hypoplasia or aplasia of the olfactory bulbs and tracts. MRI is also useful to exclude hypothalamic or pituitary lesions as the cause of hypogonadotrophic hypogonadism.
Genetic testing KS results from gene defects such as KAL1, FGFR1, PROKR2, PROK2, CHD7, and FGF8 which can be detected by genetic testing methods like Deletion/duplication analysis and Sequence analysis. Genetic testing
KS results from gene defects such as KAL1, FGFR1, PROKR2, PROK2, CHD7, and FGF8 which can be detected by genetic testing methods like Deletion/duplication analysis and Sequence analysis.
Serum TSH To exclude hypothyroidism in patients with amenorrhoea Serum TSH
To exclude hypothyroidism in patients with amenorrhoea
LH-RH stimulation test Patients with hypogonadotrophic hypogonadism show a suboptimal increase in serum LH level in response to LH-RH stimulation. LH-RH stimulation test
Patients with hypogonadotrophic hypogonadism show a suboptimal increase in serum LH level in response to LH-RH stimulation.
Anterior pituitary imaging (with either contrast enhanced computed tomography [CT] or MRI) Anterior pituitary adenomas causing hyperprolactinaemia may result in hypogonadism with clinical features similar to KS. Gadolinium-enhanced MRI should be performed to detect anterior pitutary adenomas. CT is less effective than MRI in diagnosing small adenomas, but may be used if MRI is unavailable or contraindicated. Anterior pituitary imaging (with either contrast enhanced computed tomography [CT] or MRI)
Anterior pituitary adenomas causing hyperprolactinaemia may result in hypogonadism with clinical features similar to KS. Gadolinium-enhanced MRI should be performed to detect anterior pitutary adenomas. CT is less effective than MRI in diagnosing small adenomas, but may be used if MRI is unavailable or contraindicated.

Investigations - Management

Fact Explanation
Serum LH To monitor response to treatment Serum LH
To monitor response to treatment
Serum FSH To monitor response to treatment Serum FSH
To monitor response to treatment
Serum total testosterone To monitor adequacy of testosterone replacement therapy. Serum total testosterone
To monitor adequacy of testosterone replacement therapy.
Serum estradiol in females To monitor adequacy of estrogen replacement therapy. Serum estradiol in females
To monitor adequacy of estrogen replacement therapy.
Dual-energy radiographic absorptiometry (DXA) Paients with KS are at an increased risk of developing osteoporosis. This test assesses bone mineral density and it can detect the presence of osteopenia or osteoporosis. Dual-energy radiographic absorptiometry (DXA)
Paients with KS are at an increased risk of developing osteoporosis. This test assesses bone mineral density and it can detect the presence of osteopenia or osteoporosis.
Ultrasound sacan of abdomen To detect unilateral renal agenesis (absent kidney) seen in some patients with KS. Ultrasound sacan of abdomen
To detect unilateral renal agenesis (absent kidney) seen in some patients with KS.
Smell testing To detect anosmia/hyposmia which is a key feature of KS. University of Pennsylvania smell identification test (UPSIT) is an example for a formal smell test that can be used. Smell testing
To detect anosmia/hyposmia which is a key feature of KS. University of Pennsylvania smell identification test (UPSIT) is an example for a formal smell test that can be used.
Audiometry To detect sensorineural hearing loss. Audiometry
To detect sensorineural hearing loss.
Dual-energy radiographic absorptiometry (DXA) To assess bone mineral density as patients with KS are at an increased risk of developing osteoporosis. Dual-energy radiographic absorptiometry (DXA)
To assess bone mineral density as patients with KS are at an increased risk of developing osteoporosis.
Skeletal survey To detect limb/spine bony abnormalities. Skeletal survey
To detect limb/spine bony abnormalities.

Management - Supportive

Fact Explanation
Genetic Counseling Genetic counselling involves providing individuals and families with information on the nature, inheritance, and implications of KS to help them make informed medical and personal decisions. Genetic Counseling
Genetic counselling involves providing individuals and families with information on the nature, inheritance, and implications of KS to help them make informed medical and personal decisions.
Calcium and vitamin D Individuals with KS have an increased risk to develop osteoporosis. There fore optimal calcium and vitamin D intake should be encouraged. Calcium and vitamin D
Individuals with KS have an increased risk to develop osteoporosis. There fore optimal calcium and vitamin D intake should be encouraged.
Bisphosphonates Treatment with bisphosphonates should be considered in KS patients who have decreased bone mass. Bisphosphonates
Treatment with bisphosphonates should be considered in KS patients who have decreased bone mass.
Psychological counseling This is helpful in patients who have problems coping with thier condition. Psychological counseling
This is helpful in patients who have problems coping with thier condition.

Management - Specific

Fact Explanation
Hormone replacement therapy to initiate and maintain, virilisation in males and breast development in females To initiate virilisation, testosterone replacement therapy is given for males. Human chorionic gonadotropin (hCG)is an alternative to testosterone therapy.
For females initial treatment should consist of unopposed estrogen replacement to allow optimal breast development. Once this is achieved a progestin is added for endometrial protection.
Hormone replacement therapy to initiate and maintain, virilisation in males and breast development in females
To initiate virilisation, testosterone replacement therapy is given for males. Human chorionic gonadotropin (hCG)is an alternative to testosterone therapy.
For females initial treatment should consist of unopposed estrogen replacement to allow optimal breast development. Once this is achieved a progestin is added for endometrial protection.
Hormone replacement therapy to induce and maintain fertility Both males and females with KS are given either gonadotropin therapy or pulsatile GnRH therapy to induce and maintain fertility. This treatment helps to achieve spermatogenesis in males and ovulation in females. Hormone replacement therapy to induce and maintain fertility
Both males and females with KS are given either gonadotropin therapy or pulsatile GnRH therapy to induce and maintain fertility. This treatment helps to achieve spermatogenesis in males and ovulation in females.

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