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Disease Profile

Kallmann syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Childhood

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ICD-10

E23.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Kallmann's syndrome; Anosmic hypogonadism; Anosmic idiopathic hypogonadotropic hypogonadism;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Female Reproductive Diseases;

Summary

Kallmann syndrome (KS) is a condition that causes hypogonadotropic hypogonadism (HH) and an impaired sense of smell. HH affects the production of the hormones needed for sexual development. It is present from birth and is due to deficiency of gonadotropin-releasing hormone (GnRH). KS is often diagnosed at puberty due to lack of sexual development. It may first be suspected in infancy in males with undescended testicles or a small penis. Symptoms in untreated, adult males may include decreased bone density and muscle mass; small testicles; erectile dysfunction; low sex drive; and infertility. Untreated adult females with KS usually do not have menstrual periods (amenorrhea) and normal, little, or no breast development. Rarely, a person with KS will have failure of kidney development (renal agenesis); hearing impairment; cleft lip or palate; and/or dental abnormalities. Most cases of KS are sporadic (not inherited) but some cases are inherited. The mode of inheritance depends on the gene involved. Treatment includes hormone replacement therapy for sexual development. Fertility can be achieved in most cases.[1][2]

When the features of Kallmann syndrome are not accompanied by impaired sense of smell, the condition is referred to as idiopathic or isolated hypogonadotropic hypogonadism, or normosmic isolated GnRH deficiency (IGD).

Symptoms

Kallmann syndrome (KS) is not a life-threatening condition. The main features are delayed or absent signs of puberty, and absent or diminished sense of smell (anosmia or hyposmia, respectively).

Males with KS may have signs of the condition at birth, such as undescended testes or a smaller than average penis. However, most cases are diagnosed at the time of puberty due to lack of sexual development. Males usually have no growth of facial or body hair, and decreased growth of pubic hair and genitals. They also have a delayed pubertal growth spurt in comparison to their peers. If not treated, adult males may have decreased bone density and muscle mass; decreased testicular volume; erectile dysfunction; low sex drive; and infertility.[1][3]

Females with KS usually have absent breast development, an attenuated growth spurt, decreased pubic hair growth, and no initiation of menses (primary amenorrhea). However, some females partially undergo puberty with the beginning of breast development that fails to progress. Very occasionally, affected females have onset of menses at an appropriate age, but it stops after a few cycles.[3]

In both males and females, development of pubic hair can be normal because it is controlled by secretion of androgens from the adrenal glands, which are not affected by the condition.[3] Almost all untreated people with KS are infertile, but fertility can be restored in those that respond to certain treatments.[4]

Some people with KS have any of various non-reproductive features. These may include:

  • cleft lip and palate
  • renal agenesis (one kidney does not develop)
  • hearing impairment
  • dental abnormalities
  • eye movement abnormalities
  • poor balance
  • scoliosis (curvature of the spine)
  • synkinesis of the hands, in which the movements of one hand are mirrored by the other hand[1][3][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anosmia
Lost smell
0000458
Anterior hypopituitarism
0000830
Decreased fertility
Abnormal fertility
0000144
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Erectile dysfunction
Abnormal erection
Erectile abnormalities

[ more ]

0100639
Hypogonadotropic hypogonadism
0000044
Hyposmia
0004409
Hypothalamic gonadotropin-releasing hormone deficiency
0003164
Micropenis
Short penis
Small penis

[ more ]

0000054
30%-79% of people have these symptoms
Abnormality of the voice
Voice abnormality
0001608
Breast hypoplasia
Underdeveloped breasts
0003187
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Reduced bone mineral density
Low solidness and mass of the bones
0004349
5%-29% of people have these symptoms
Abnormal morphology of female internal genitalia
0000008
Abnormality of cardiovascular system morphology
0030680
Ataxia
0001251
Bimanual synkinesia
Hand mirror movements
Mirror hand movements
Mirror movements

[ more ]

0001335
Cleft palate
Cleft roof of mouth
0000175
Color vision defect
Abnormal color vision
Abnormality of color vision

[ more ]

0000551
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Dysarthria
Difficulty articulating speech
0001260
Dyspareunia
0030016
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Gynecomastia
Enlarged male breast
0000771
Ichthyosis
0008064
Muscle weakness
Muscular weakness
0001324
Muscular hypotonia
Low or weak muscle tone
0001252
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Obesity
Having too much body fat
0001513
Paraplegia
Leg paralysis
0010550
Pes cavus
High-arched foot
0001761
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Primary amenorrhea
0000786
Ptosis
Drooping upper eyelid
0000508
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures

[ more ]

0002757
Reduced number of teeth
Decreased tooth count
0009804
Renal agenesis
Absent kidney
Missing kidney

[ more ]

0000104
Seizure
0001250
Sensorineural hearing impairment
0000407
Skeletal dysplasia
0002652
Tremor
0001337
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

0000505

Diagnosis

The diagnosis of Kallmann syndrome may be suspected with evidence of lack of sexual maturation or hypogonadism, and evidence of incomplete sexual maturity by Tanner staging. Tanner staging is an established method used by endocrinologists worldwide to evaluate the maturation of the primary and secondary sexual characteristics.[3]

The diagnosis of Kallmann syndrome additionally relies on hormone evaluation, as well as evaluation of the sense of smell (olfactory function testing). Analysis of the olfactory bulbs by MRI can be useful, especially in young children. Genetic testing can also be used to diagnose the condition by identifying a disease-causing mutation in one of the genes responsible for Kallmann syndrome.[1]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Kallmann syndrome. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Kallmann syndrome. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

            References

            1. Jean-Pierre Hardelin and Jacques Young. Kallmann syndrome. Orphanet. June, 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=478.
            2. Kallmann syndrome. Genetics Home Reference. 2008; https://ghr.nlm.nih.gov/condition/kallmann-syndrome. Accessed 12/22/2011.
            3. Kallmann Syndrome. NORD. November 14, 2012; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/848/viewAbstract.
            4. Nicholas A Tritos. Kallmann Syndrome and Idiopathic Hypogonadotropic Hypogonadism. Medscape. June 4, 2014; https://emedicine.medscape.com/article/122824-overview.
            5. Cassandra Buck, Ravikumar Balasubramanian, and William F Crowley, Jr. Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency. GeneReviews. July 18, 2013; https://www.ncbi.nlm.nih.gov/books/NBK1334/.

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