Klinefelter's syndromeQ98.40

Author:Prof. Dr. med. Peter Altmeyer

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Last updated on: 04.04.2022

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Synonym(s)

47; XXY47 syndrome; XXY syndrome; XXY Syndromes

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HistoryThis section has been translated automatically.

Klinefelter, 1942

DefinitionThis section has been translated automatically.

Syndrome characterized, among other things, by testicular developmental disorder with varying degrees of physical features based on numerical aberration of the sex chromosomes (in 80% 47, XXY; rarely 48, XXYY; 49, XXXXY or mosaic 46, XY/47, XXY) by nondisjunction either in meiotic divisions during germ cell development or in early embryonic mitotic cell divisions during maturation in phenotypically male individuals.

Occurrence/EpidemiologyThis section has been translated automatically.

Frequency: 1:500 male newborns or between 2 and 5% for infertile males (prevalence of 0.2%). Advanced age of the mother seems to be a risk factor.

Clinical featuresThis section has been translated automatically.

Prepubertal: no definite symptoms, occasional oligophrenia. On the skin, focal atrophy, pigmentary changes, nodularity.

In puberty or postpuberty: obligatory small testicles with volumes below 3-5 ml in the sense of primary testicular damage with compensatory hypergonadotropic hypogonadism ( FSH strongly increased, LH/ICSH moderately increased or normal), azoospermia or high grade oligozoospermia with mostly irreversible infertility (occasionally paternity has been described); optionally in 30-50% of cases manifest or latent testosterone deficiency with gynoid habitus ( gynecomastia with a possible increased pigmentation of the nipple-areola complex, female fat distribution pattern, female secondary hair, increased voice pitch). Furthermore, there is increased:

  • long extremities
  • Obesity
  • osteoporosis
  • Intelligence defects
  • vascular dysplasias
  • ulcers of the lower legs
  • Cutis verticis gyrata (rare)
  • Nail dysplasias
  • Wart-like papillae of the skin and mucosa (Krause W 2017).

Patients with Klinefelter syndrome have a 50-fold increased risk of developing breast cancer compared to a healthy male (Hultborn R et al 1996).

DiagnosisThis section has been translated automatically.

Molecular genetic examination, family history, clinic

Obligatory reduced testicular volume (below 3-5 ml); azoospermia or high-grade oligozoospermia, hypotestosteronemia, FSH elevation, testicular biopsy with excessive tubular sclerosis and hyperplasia of v. Leydig's intermediate cells, oral mucosal smear with detection of one or more chromatin bodies in the cell nuclei, chromosome analysis.

Differential diagnosisThis section has been translated automatically.

Secondary testicular damage, testicular dysgenesis of other cause, gynecomastia of other cause.

TherapyThis section has been translated automatically.

If the testosterone level is low or the serum LH level > 7 mU/ml, start testosterone substitution therapy at about 11 years of age, see Table 1.

The dosages for children are guidelines which must always be adjusted to the clinical situation (growth in length, ossification, psychosexual development). For monitoring of testosterone substitution, see Kallmann syndrome. The treatment must be carried out for life. A special therapeutic case is formed by patients with criminal convictions, who should receive carefully monitored substitution therapy. If the patient wishes to have children, sperm can be searched for in the testicular tissue and, if necessary, vital sperm can be obtained from a small testicular biopsy for intracytoplasmic sperm injection using the TESE (testicular sperm extraction) technique.

Gynecomastia remains unaffected by testosterone substitution and may need to be addressed surgically. Careful monitoring of these patients as the risk of developing breast carcinoma is increased 20-fold compared to normal men.

Extragonadal germ cell tumors (mediastinal nonseminomatous germ cell tumors, intracerebral germ cell tumors) must be addressed surgically.

TablesThis section has been translated automatically.

Testosterone substitution in Klinefelter syndrome

Age

Application

Example preparation

Dosage

11th year of age

orally

Andriol

40 mg/day

Alternatively:

Proviron

12.5 mg/day

age 12

orally

Andriol

40 mg 2 times/day

Alternatively:

Proviron

12.5 mg 2 times/day

from the age of 13 up

orally

Andriol

40 mg 2 times/day

Alternatively:

Proviron

25 mg 2 times/day

Alternatively:

i.m.

Testoviron

100 mg/month

Adults

i.m.

Testoviron Depot 250 mg

every 2-3 weeks

Alternatively:

Testosterone Depot 250 mg

every 2-3 weeks

Alternatively:

p.o.

Andriol

24 kps/day

Alternatively:

transdermal

Testogel

25-50 mg/day

Alternatively:

Androderm

2 Membranes/day

Note(s)This section has been translated automatically.

X-linked genodermatoses

The genes of one of the two X chromosomes in females are usually inactivated (lyonization). X-linked dermatoses that are lethal to male descendants can therefore only be observed in females. These include the following syndromes:

  • Incontinentia pigmenti
  • Focal dermal hpoplasia
  • Conradi-Hünermann-Happle syndrome
  • Oral-facial-digital syndrome
  • MIDAS (microphthalmia, dermal aplasia, sclerocornea) syndrome.

Other non-lethal x-linked disorders include:

  • Hypohidrotic ectodermal dysplasia Christ-Siemens-Touraine
  • IFAP syndrome (ichthyosis, follicular alopecia, photophobia)
  • Dyskeratosis congenita
  • Since 2 or > 2 X chromosomes are present in Klinefelter syndrome, there is a possibility that male children may also survive with one of the syndromes that are lethal to male descendants. Incontinentia pigmenti and focal hypoplasia have been described (Krause W 2017).

LiteratureThis section has been translated automatically.

  1. Amory JK (2000) Klinefelter's syndrome. Lancet 356: 333-335
  2. Christiansen P (2003) Longitudinal studies of inhibin B levels in boys and young adults with Klinefelter syndrome. J Clin Endocrinol Metab 88: 888-891
  3. De Geyter CH et al (1996): Assisted fertilisation. In: Nieschlag, E., Behre HM (eds.) Andrology - Principles and Clinic of Male Reproductive Health. Springer-Verlag, Berlin, Heidelberg, New York, S. 350-353
  4. Hultborn R et al (1997) Prevalence of Klinefelter's syndrome in male breast cancer patients. Anticancer Res 17:4293-4297.
  5. Keller K et al (2001) Klinefelter's syndrome and cutis verticis gyrata. At J Med Genet 103: 249-251
  6. Klinefelter HF, Reifenstein EC Jr, Albright F Jr (1942) Syndrome characterized by gynaecomastia, aspermatogenesis without A-Leydigism and increased excretion of follicle-stimulating hormones. Journal of Clinical Endocrinology (Baltimore) 2: 615-627
  7. Krause W (2017) Skin diseases in Klinefelter's syndrome. Close Dermatology 33:32-35

  8. Nieschlag E et al (1996): Disturbances in the area of the tests. In: Nieschlag E, Behre HM (eds.) Andrology - Principles and Clinic of Male Reproductive Health. Springer-Verlag, Berlin, Heidelberg, New York, S. 153-154 and 315-329

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Last updated on: 04.04.2022