Chapter 24: genetic disorders Flashcards
Genetic disorder
Genetic disorders arise from a congenital defect in the chromosomes or genes, which can be hereditary, but also because of a spontaeous change in the genetic material.
A cell contains of 46 chromosomes (23 pairs), which are made up of DNA and are located in the nucleus of every cell. DNA is made up of a genetic code, for example for production of amino acids (the basic elements of proteins). Proteins then form the basis for cells tat are involved in a variety of regulation processes in the body.
Monosomy
One of the 2 chromosomes that form a pair is absent.
Trisomy
One pair of chromosomes has an extra chromosome.
Chromosomal disorder
Caused by the partial or complete absence or duplication of a chromosome.
Monogenic disorder
Caused by a mutation in a single gene. This can be inhereted in several ways.
- Autosomal dominant inheritance: one of the parents carries the gene mutation and has the condition (50% chance for the children).
- Autosomal recessive inheritance: both paents carry the gene, but don’t have the condition (25% chance for the children).
- X-linked inheritance: the mutated gene lies on the X-chromosome.
X-linked inheritance
X-linked inheritance; the mutated gene lies on the X-chromosome. In the recessive inheritance pattern where the mother carries the gene mutation, but does not have the condition, her sons have a 50% chance of inheriting the disorder and her daughters have a 50% probability of carrying the mutated gene. If the father carries the gene mutation, he will have the disorder and pass the gene mutation to his daughters that don’t have the disorder and his sons will be unaffected.
In the dominant inheritance pattern where that father carries the gene mutation, he will have the disorder and pass it on to his daughters, but his sons will be unaffected. If the mother carries the gene mutation, she has the disorder and her sons and daughters have a 50% chance of being affected.
Polygenic disorders
Caused by a combination of different genetic mutations and gene-environment interactions (is hereditary).
Mitochondrial disorder
Caused by a mutation in DNA that is located outside of the cell nucleus: in the mitochondria.
Reasons for referral for genetic testing
- Developmental problems in children (ASD, schizophrenia etc.)
- Craniofacial anomalies or other unusual external features.
- Looking at the inheritance pattern to determine if a gene is dominant of recessive, if women or men would be more affected or if the patient’s condition appears in a family with no previous medical problems.
Cognitive problems
The abnormalities in genetic material can lead to the disruption of brain development or to brain dysfunction. This causes problems in language, executive functioning, social-cognitive functioning and hyperactivity or impulse behaivor.
Noonan syndrome
People with Noonan have a congenital disorder, a short height and atypical facial features (widely spread eyes, drooping eyelids, low-set ears and a thick. neck). Patients also have a bigger chance of epilepsy and Chiari malformation type 1: a part of the cerebellum extends downward into the uppermost part of the spinal column.
Genetics in Noonan’s disorder / syndrome
A monogenic disorder caused by mutation in genes that are involves in the mitogen-activated protein kinase pathways. 17 genes have been identified in which mutations can lead to this syndrome. It can be because of spontaneous mutation or familial inhertitance. The kinase pathway gene is involved in learning and memory.
Cognitive impairments in Noonan’s
About 1/3 of patients receive special education, but somitimes patients can have an above-average intelligence. They often show feeding problems in infancy and delay in development of language and motor skills. Other deficits can be:
- Visual processing
- Attention
- Learning
Memory
- Executive functioning
- Social cognitive functions
- Hypteractive
- Inattentive
- Impulsive
- Introverted
Neurofibromatosis type 1 (NFI)
An autosomsal dominant heriditary disorder that is caused by a mutation in the NFI gene on chromosome 17, but can also be caused spontaneously. It is diagnosed if 2 or more symptoms exist:
- 6+ spots on the skin,
- 2+ neurofibromas
- freckles in the armpits and or groin
- tumor in the optic nerve
2+ lish nodules (pigment cells in the iris)
- bone abnormalities
or a first degree familiiy member with NFI.
Neurofibromatosis type 1 brain area’s
Patients have a larger brain volume, but they do have dysfunction in the right inferior frontal regions and medio-frontal eras, abnormalities in the anterior thalamic radiation and dysfunction of the visual cortex.
