Genetic imprinting disorders are a group of conditions caused by the abnormal expression of genes that are imprinted, meaning they are expressed only from either the maternal or paternal allele, not both. These disorders result from errors in the process of imprinting or in the maintenance of imprinting over generations.
Here are some key disorders of genetic imprinting :
1. Prader-Willi Syndrome (PWS)
- Causes: PWS is caused by the loss of function of a set of genes on chromosome 15. In most cases, the deletion occurs on the paternal chromosome. If the deletion occurs on the maternal chromosome, the child will not develop PWS, indicating the importance of the paternal contribution to this syndrome.
- Symptoms: Characterized by hypotonia, poor feeding in infancy, developmental delay, intellectual disability, short stature, obesity, hypogonadism, and behavioral issues.
2. Angelman Syndrome (AS)
- Causes: AS is caused by a similar deletion on chromosome 15 but on the maternal chromosome. The paternal allele of the UBE3A gene (involved in protein degradation) is normally silenced, and its loss leads to the syndrome.
- Symptoms: Features include severe developmental delay, speech impairment, ataxia, seizures, and a happy, excitable personality.
3. Beckwith-Wiedemann Syndrome (BWS)
- Causes: BWS results from abnormal imprinting or mutations in genes like IGF2, which are on chromosome 11. It often involves a loss of methylation on the paternal allele or gain of methylation on the maternal allele.
- Symptoms: Symptoms include macrosomia, macroglossia, abdominal wall defects, and an increased risk of childhood cancers like Wilms’ tumor and hepatoblastoma.
4. Silver-Russell Syndrome (SRS)
- Causes: SRS is associated with a loss of methylation at the imprinting control region 1 (ICR1) on chromosome 11 or mutations in the CDKN1C gene.
- Symptoms: Growth retardation, triangular face, clinodactyly (curved fifth finger), and relative macrocephaly.
5. Temple Syndrome (TS)
- Causes: TS is caused by mutations or deletions in the SNRPN gene on chromosome 15.
- Symptoms: Similar to PWS but milder and includes developmental delay and behavioral issues.
Mechanisms of genetic Imprinting Disorders:
- Deletion: Loss of a gene on one chromosome, which can happen on either the maternal or paternal chromosome.
- Uniparental Disomy: Both chromosomes come from one parent instead of one from each parent.
- Methylation defects: Improper addition or maintenance of methyl groups to the DNA, leading to inappropriate gene silencing or expression.
- Mutations in imprinting control regions: Disruption in the regulatory sequences that control the parent-specific expression of genes.
These disorders highlight the critical nature of genetic imprinting in normal development. The treatments for these conditions are primarily supportive, addressing symptoms and managing any associated developmental and physical complications.
Pingback: Enzyme Replacement Therapy (ERT):Best article 2025 - MASTERPEDIATRICS
Pingback: Classification of Vasculitis Based on Size of Involved Vessels: Best article 2025 - MASTERPEDIATRICS