Swyer syndrome

from Wikipedia, the free encyclopedia
Classification according to ICD-10
Q99.1 Hermaphroditism verus with karyotype 46, XY
Q56.4 Undetermined gender, unspecified -

Genitalia not clearly differentiable

ICD-10 online (WHO version 2019)

The XY gonadal dysgenesis is a by mutation in the Y chromosome caused pure form of XY gonadal dysgenesis , a gonad - malformation , which can not be passed because of the infertility of those affected. The main characteristics are male core sex , but female appearance and lack of puberty .

The mutation occurs during spermatogenesis in the father or in the fertilized egg. Those affected appear purely outwardly as girls, develop to a normal size and show no additional deformities. During puberty , however, there is no development of secondary sexual characteristics and no menstrual period ( primary amenorrhea ), they are sterile for life ( sterility ), and the external sexual organs remain childlike ( genital infantilism ). An examination of the chromosomes reveals a male (46, XY) chromosome set ( karyotype ) , contrary to the female appearance .

Synonyms are: Swyer phenotype; 46, XY pure gonadal dysgenesis; 46, XY-CGD

The name refers to an initial description from 1955 by the British endocrinologist Gerald JM Swyer.

Occurrence

The frequency is estimated at 1 in 80,000.

root cause

The cause is not fully known; it is based on a break in the genetic signal chains with no test development.

Classification

Depending on the detected mutation, the following classification can be made:

  • Type 1 , COMPLETE, SRY-related, with mutation in the SRY - gene in the Y chromosome in locus p11.2
  • Type 2 with a partial duplication including the NR0B1 gene in the X chromosome at locus p21.2
  • Type 3 , COMPLETE OR PARTIAL, WITH OR WITHOUT ADRENAL FAILURE, with mutations in the NR5A1 gene in chromosome 9 at locus q33.3
  • Type 4 , COMPLETE OR PARTIAL, WITH 9p24.3 DELETION, with deletions in chromosome 9 at locus p24.3
  • Type 5 , COMPLETE, CBX2-RELATED, with mutations in the CBX2 gene in chromosome 17 at locus q25.3
  • Type 6 with mutations in the MAP3K1 gene in chromosome 5 at locus q11.2
  • Type 7 , COMPLETE OR PARTIAL, DHH-RELATED, with mutations in the DHH gene in chromosome 12 at locus q13.12
  • Type 10 , autosomal dominant , with mutations in chromosome 17 at locus q24

In addition, environmental factors (maternal progesterone intake during pregnancy) and disturbed prenatal growth have been linked to the syndrome.

Clinical manifestations

A person with Swyer syndrome initially develops completely normally as an embryo in the womb. Only in the 7th / 8th At the embryonic week a change occurs. Due to a genetic defect, which is mostly due to the SRY gene , no hormone-active gonads (testes) can be developed, so that development into men is not possible. So the “basic woman program” comes into play. The rest of the way is as if the embryo were a female individual.

The clitoris, labia , vagina and uterus develop . However, the gonads do not develop into ovaries . Instead, there are so-called streak gonads (= connective tissue strands) in their place .

After the birth, the child develops normally and is completely normal from the outside.

The following effects only occur in puberty due to the lack of ovaries / female hormones:

  • Primary amenorrhea occurs (lack of menstrual bleeding) and secondary sex development does not occur.
  • Furthermore, normal or tall stature can occur with eunuchoid body proportions.
  • The lack of sex hormones leads to a tendency towards osteoporosis.
  • There is a risk of developing malignant gonadal tumors ( dysgerminoma or gonadoblastoma ) from the first decade of life (according to some statements up to 30% risk), which is why it is usually recommended to remove both gonads early.

diagnosis

The diagnosis results from the clinic together with the evidence of hypergonadotropic hypogonadism , the hormone determinations and the karyogram .

treatment

Part of the treatment is the removal of the strand gonades, as they pose a high risk of malignant degeneration. Possible associated health problems (e.g. renal insufficiency in Frasier syndrome or associated malformations) must be treated depending on the genetic diagnosis. Hormone substitution is recommended at the time of puberty. To this end, the patients and their families should also be offered psychological help. Infertility is an important issue in treatment. However, egg donation can lead to pregnancies. Hormone substitution (usually combination products with estradiol and norethisterone acetate) can activate physical development and, depending on the drug, initiate a female cycle, whereby infertility remains due to the lack of ovaries. Secondary sexual characteristics (e.g. female breast) develop. The risk of osteoporosis is reduced.

forecast

Swyer sufferers can lead a completely normal life. Life expectancy is not reduced. Due to the above problem, however, hormones should be taken for life.

Due to the lack of ovaries, it is not possible for Swyer sufferers to become pregnant or have biological children. The uterus, however, theoretically makes it possible to carry a child to term after egg donation.

With appropriate treatment, the risk of malignancy can be kept low.

Differential diagnosis

Other forms of gonadal dysgenesis must be differentiated, such as gonadal dysgenesis, 46, XX type , Frasier syndrome or Kampomele dysplasia .

See also

literature

  • Manfred Stauber, Thomas Weyerstahl: Gynecology and Obstetrics. Dual series, Georg Thieme Verlag (2001), 36. ISBN 3-13-125341-X

Individual evidence

  1. ↑ a b Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
  2. ↑ a b c d e f 46, XY Gonadal Dysgenesis, complete. In: Orphanet (Rare Disease Database).
  3. ^ GI Swyer: Male pseudohermaphroditism: a hitherto undescribed form. In: British medical journal. Volume 2, Number 4941, September 1955, pp. 709-712, PMID 13250193 , PMC 1980764 (free full text).
  4. ↑ 46XY sex reversal 1.  In: Online Mendelian Inheritance in Man . (English)
  5. ↑ 46XY sex reversal 2.  In: Online Mendelian Inheritance in Man . (English)
  6. ↑ 46XY sex reversal 3.  In: Online Mendelian Inheritance in Man . (English)
  7. ↑ 46XY sex reversal 4.  In: Online Mendelian Inheritance in Man . (English)
  8. ↑ 46XY sex reversal 5.  In: Online Mendelian Inheritance in Man . (English)
  9. ↑ 46XY sex reversal 6.  In: Online Mendelian Inheritance in Man . (English)
  10. ↑ 46XY sex reversal 7.  In: Online Mendelian Inheritance in Man . (English)
  11. ↑ 46XY sex reversal 10.  In: Online Mendelian Inheritance in Man . (English)

Web links