BWS and russel-silverman lecture M2C

What syndrome is characterized by overgrowth, macrosomia, and increased risk for embryonic tumors?

Beckwith-Wiedemann syndrome (BWS)

What are some clinical features of Beckwith-Wiedemann syndrome?

Macrosomia, hemihyperplasia, macroglossia, omphalocele, neonatal hypoglycemia, and increased risk for tumors.

What genetic mechanism is often involved in Beckwith-Wiedemann syndrome?

Loss of maternal methylation at imprinting control regions (IC1, IC2) affecting the CDKN1C gene.

What is the recurrence risk associated with paternal uniparental disomy (UPD) in BWS?

Paternal UPD is associated with a high recurrence risk.

What is Silver-Russell syndrome (SRS) often described as?

A form of primordial dwarfism and the phenotypic opposite of Beckwith-Wiedemann syndrome.

What are some clinical features of Silver-Russell syndrome?

Significant short stature, body asymmetry, relative macrocephaly, feeding difficulties, and potential learning difficulties.

What is the primary genetic cause of Silver-Russell syndrome?

Loss of paternal methylation on chromosome 11p15.5.

What is Fragile X syndrome known for?

It is the most common cause of inherited intellectual disability and autism.

What are some physical features associated with Fragile X syndrome?

Large head circumference, large ears, macrocephaly, long face, and large testes.

What genetic change causes Fragile X syndrome?

Changes in the FMR1 gene, specifically a trinucleotide repeat expansion (CGG repeats).

What is the phenomenon of anticipation in Fragile X syndrome?

Increased risk of CGG repeat expansion with each generation when inherited from the mother.

What is the recurrence risk for an unaffected carrier male of Fragile X syndrome to have an affected child?

Less than 1%.

What is the chance for an affected male with Fragile X syndrome to have an affected child?

Approximately 50% chance.

What role does FMRP play in Fragile X syndrome?

FMRP represses translation of mRNA for synaptic proteins and regulates mRNA localization.

What is the relationship between CDKN1C expression and Silver-Russell syndrome?

Increased CDKN1C expression (maternal) may lead to Silver-Russell syndrome.

What are the potential health risks for females with Fragile X syndrome?

Premature ovarian insufficiency and Fragile X Tremor Ataxia Syndrome.

What is the significance of methylation studies in diagnosing BWS?

They detect abnormalities in IC1 and IC2 methylation, which can help determine the cause of BWS.

What types of genetic tests may be needed to determine the cause of Beckwith-Wiedemann syndrome?

Methylation studies, sequencing of CDKN1C, and karyotype/microarray analysis.

What is the impact of duplications of ICR1 and ICR2 on maternal and paternal chromosomes?

Duplication on maternal chromosome results in Silver-Russell syndrome; on paternal chromosome results in BWS.

What is the typical onset age for Fragile X Tremor Ataxia Syndrome (FXTAS)?

Typically after age 50.

What is the role of mGluR-1 in the context of Fragile X syndrome?

Increased mGluR-1 activity can lead to long-term depression (LTD) of synapses, affecting cognition and memory.

What are the implications of point variants in the CDKN1C gene?

They can lead to different outcomes, including BWS or Silver-Russell syndrome, depending on the nature of the mutation.

What is the importance of understanding genotype-phenotype correlations in genetic disorders?

It helps in predicting clinical implications and recurrence risks associated with genetic conditions.

What is the significance of the term 'loss of function' in genetic mutations?

It refers to mutations that result in reduced or abolished gene function, often leading to disease.

What does 'gain of function' mutation imply in the context of genetic disorders?

It refers to mutations that enhance the normal function of a gene, potentially leading to conditions like Silver-Russell syndrome.

Why is it important to consider multiple genetic mechanisms for the same disease?

Different genetic alterations can lead to similar clinical presentations, affecting diagnosis and treatment.