Genetics · MU Sofia

41. Chromosomal diseases caused by sex chromosome aberrations: monosomy X, Klinefelter syndrome, Fraccaro syndrome, polysomy X, polysomy Y.

Covers numerical sex chromosome aberrations and why they are often compatible with life, starting with general mechanisms (nondisjunction and mosaicism) and pathophysiology. It then goes through monosomy X, Klinefelter, Fraccaro, polysomy X and polysomy Y in turn, giving each one's karyotype, clinical features, diagnosis and management where relevant. Eight pictures accompany the sections, and the note also notes that the old idea of heightened aggression in XYY males is not supported by science.

Inside: 8 sections · 8 labelled pictures · 15 flashcards · 5 min

Topic 41 of 65 in the MU Sofia syllabus for Genetics (Medicine, Year 3). The free AceMed note covers it in 8 sections, about 622 words (5 min of reading), with 15 flashcards.

In this note

  1. Chromosomal diseases caused by sex chromosome aberrations: monosomy X, Klinefelter syndrome, Fraccaro syndrome, polysomy X, polysomy Y.
  2. General Mechanisms
  3. General Pathophysiology
  4. I. MONOSOMY X (TURNER SYNDROME)
  5. II. KLINEFELTER SYNDROME
  6. III. FRACCARO SYNDROME (48,XXYY)
  7. IV. POLYSOMY X (TRIPLE X SYNDROME)
  8. V. POLYSOMY Y (47,XYY SYNDROME)

Chromosomal diseases caused by sex chromosome aberrations: monosomy X, Klinefelter syndrome, Fraccaro syndrome, polysomy X, polysomy Y.

Sex chromosome aberrations are chromosomal disorders caused by numerical abnormalities of the X or Y chromosomes. They result from meiotic nondisjunction or postzygotic mitotic errors, leading to aneuploidy.

Unlike autosomal aneuploidies, sex chromosome disorders are often compatible with life because:

  • one X chromosome is normally inactivated (X-inactivation),
  • the Y chromosome carries relatively few genes.

General Mechanisms

1. Nondisjunction

  • Failure of sex chromosomes to separate during meiosis I or II.
  • Leads to gametes with abnormal chromosome numbers.

2. Mosaicism

  • Postzygotic mitotic nondisjunction.
  • Produces two or more cell lines (e.g., 45,X / 46,XX).

General Pathophysiology

  1. 1. Abnormal number of sex chromosomes alters gene dosage.
  2. 2. Genes escaping X-inactivation are over- or under-expressed.
  3. 3. Gonadal development is particularly affected.
  4. 4. Leads to abnormalities in sexual development, fertility, and growth.
  5. 5. Cognitive effects are usually milder than autosomal trisomies.

I. MONOSOMY X (TURNER SYNDROME)

Monosomy X (Turner syndrome) is a chromosomal disorder characterized by the complete or partial absence of one X chromosome, resulting in a female phenotype with gonadal failure.

Karyotype

  • 45,X (classic form)
  • Mosaic forms: 45,X / 46,XX, 45,X / 46,XY

Genetic Basis

  • Loss of genes normally present on both X chromosomes.
  • Especially important: genes in the pseudoautosomal regions (PAR) that escape X-inactivation.

Pathophysiology

  1. 1. Absence of second X → reduced gene dosage.
  2. 2. Failure of normal ovarian development.
  3. 3. Streak gonads replace functional ovaries.
  4. 4. Estrogen deficiency affects growth and sexual maturation.

Clinical Features

General

  • Short stature
  • Webbed neck
  • Low posterior hairline
  • Broad chest with widely spaced nipples

Gonadal

  • Streak ovaries
  • Primary amenorrhea
  • Infertility

Cardiovascular

  • Coarctation of the aorta
  • Bicuspid aortic valve

Renal

  • Horseshoe kidney

Cognitive

  • Normal intelligence
  • Difficulties with visuospatial skills

Diagnosis

  • Karyotyping (prenatal or postnatal).
  • Elevated FSH and LH (hypergonadotropic hypogonadism).

Management

  • Growth hormone therapy in childhood.
  • Estrogen replacement for pubertal development.
  • Cardiac and renal monitoring.

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