Medical Genetics · MU Plovdiv

9. Chromosomal pathology. Chromosomal diseases associated with aberrations of gonosomes, MGC.

Inside: 8 sections · 8 labelled pictures · 15 flashcards · 4 min

Topic 9 of 33 in the MU Plovdiv syllabus for Medical Genetics (Medicine, Year 4). The free AceMed note covers it in 8 sections, about 600 words (4 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. Abnormal number of sex chromosomes alters gene dosage.
  2. Genes escaping X-inactivation are over- or under-expressed.
  3. Gonadal development is particularly affected.
  4. Leads to abnormalities in sexual development, fertility, and growth.
  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. Absence of second X → reduced gene dosage.
  2. Failure of normal ovarian development.
  3. Streak gonads replace functional ovaries.
  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.

Continue reading free

The whole note, all 8 sections, is free with an AceMed account, with its 15 flashcards. Premium adds flashcard recall, highlights and Ask AI.

Start freeAlready a member? Open the note