Kallmann syndromeE23.07

Author:Prof. Dr. med. Peter Altmeyer

All authors of this article

Last updated on: 26.10.2021

Dieser Artikel auf Deutsch

Requires free registration (medical professionals only)

Please login to access all articles, images, and functions.

Our content is available exclusively to medical professionals. If you have already registered, please login. If you haven't, you can register for free (medical professionals only).


Requires free registration (medical professionals only)

Please complete your registration to access all articles and images.

To gain access, you must complete your registration. You either haven't confirmed your e-mail address or we still need proof that you are a member of the medical profession.

Finish your registration now

HistoryThis section has been translated automatically.

Kallmann et al., 1943; de Morsier, 1954

DefinitionThis section has been translated automatically.

Hereditary syndrome with genetically determined association of hypogonadotropic hypogonadism and anosmia.

Occurrence/EpidemiologyThis section has been translated automatically.

Incidence (male sex): 1/10,000 births; Incidence (female sex): 1/50,000 births.

EtiopathogenesisThis section has been translated automatically.

The cause of KS is a developmental disorder of the olfactory system and an interrupted embryonic migration of GnRH-synthesizing neurons from the olfactory epithelium to the hypothalamic region. Most cases are sporadic, but familial forms have been described. Causative genes are

in the X-linked recessive form KAL1 (Xp22.32)

in the autosomal dominant form FGFR1 (8p12), FGF8 (10q25-q26), CHD7 (8q12.2) and SOX10 (22q13.1)

in the autosomal recessive and oligogenic form PROKR2 (20p12.3) and PROK2 (3p21.1).

Whether other genes (e.g. SEMA3A) are involved in the genesis of KS has not yet been clarified.

ManifestationThis section has been translated automatically.

Little penetrance in the female sex. Men are affected about 5-6 times as often as women.

Clinical featuresThis section has been translated automatically.

The leading symptom is absent or incomplete pubertal development with pronounced secondary hypogonadism (testicular volume around 3 ml, underdevelopment of the penis and prostate, absent or slightly pronounced secondary body hair, eunuchoid growth, feminine fat distribution pattern), often unilateral or bilateral cryptorchidism (see maldescensus testis) or condition after orchidopexy, rarely gynecomastia. Without therapy there is impotentia gestandi ( aspermia or azoospermia).

Second cardinal symptom is hypo- or anosmia (based on aplasia or hypoplasia of the bulbi and tractus olfactorii). In addition, synkinesia, pes cavus, unilateral renal agenesis, unilateral vas deferens aplasia, cleft lip and palate, and patchy hyperpigmentation of the skin are common.

Some patients present with skin lesions of X-linked recessive ichthyosis.

DiagnosticsThis section has been translated automatically.

Hormone analyses (sex hormones, gonadal peptides, pituitary gonadotropin test) and examination of the sense of smell (olfactometry) lead to the diagnosis. Morphologic analysis of the olfactory bulbs by MRI may be helpful, especially in young children. Genetic testing can identify a mutation-causing disease and is mandatory before starting infertility treatment.

Prenatal diagnosis: In a familial setting with FGFR1, FGF8, KAL1 or CHD7 mutations, bone abnormalities, cleft lip/palate, renal agenesis or multiple developmental defects in the fetus can be detected by ultrasound examination.

TherapyThis section has been translated automatically.

For newly diagnosed patients, initiation of testosterone therapy lasting several months with the aim of providing the patient with an optimal supply of testosterone and rapid virilization, see below. gonadal dysgenesis.

LiteratureThis section has been translated automatically.

  1. De Morsier G (1954) Études sur les dysraphies crânio-encephaliques. I. Agénésie des lobes olfactifs (télencéphaloschizis latéral) et des commissures calleuse et antérieure (télencéphaloscizis median). La dysplasia olfacto-génitale. Schw Arch Neurol Psych (Zurich) 74: 309-361
  2. Hu Y et al (2003) Kallmann's syndrome: molecular pathogenesis. Int J Biochem Cell Biol 35: 1157-1162
  3. Kallmann FJ, Schönfeld WA, Barrera SE (1944) The genetic aspects of primary eunuchoidism. At J Mental Deficiency 48: 203-236
  4. Maya-Nunez G et al (1999) An atypical contiguous gene syndrome: molecular studies in a family with X-linked Kallmann's syndrome and X-linked ichthyosis. Clin Endocrinol (Ox) 50: 157-162
  5. Silveira LF et al (2002) Hypogonadotropic hypogonadism. Semin Reprod Med 20: 327-338
  6. Weidenreich F (1914) On partial olfactory lobe defects and eunuchoidism in humans. Morphol Anthropol (Stuttgart) 18: 157
  7. Weissortel R et al (1998) Analysis of an interstitial deletion in a patient with Kallmann syndrome, X-linked ichthyosis and mental retardation. Clin Genet 54: 45-51

Authors

Last updated on: 26.10.2021