Human Somatic Mosaicism and Syndromes

Questions and Answers

What is a key characteristic of ovarian function in females with Turner Syndrome?

Ovaries have normal levels of hormonal production

Ovaries are enlarged due to cysts

Ovaries are elongated and contain abundant stromal tissue (correct)

Ovaries contain multiple healthy follicles

Which percentage of Turner Syndrome patients are likely to achieve puberty?

Approximately 30%

Over 50%

Less than 10% (correct)

All patients develop normally

What gene is associated with short stature in Turner Syndrome patients?

SHOX (correct)

IGF1

FGFR3

GH1

What is a common complication observed in up to 50% of patients with Turner Syndrome?

Osteoporosis Signup and view all the answers

What clinical sign is frequently observed in newborns with Turner Syndrome?

Lymphedema Signup and view all the answers

What is a common feature of the somatic mosaicism in normal individuals?

Low level with less than 2% affected cells Signup and view all the answers

Which condition is characterized by primary amenorrhea due to ovarian failure?

Turner Syndrome Signup and view all the answers

What is the expected effect of the SHOX gene on individuals with Turner Syndrome?

Short stature due to a single copy of the gene Signup and view all the answers

Which of the following statements accurately describes Klinefelter syndrome?

It is characterized by tall stature and hypogonadism. Signup and view all the answers

What is the prevalence of the XXX karyotype in the population?

1 in 1200 Signup and view all the answers

How does the presence of additional copies of the SHOX gene affect males with Klinefelter syndrome?

Contributes to increased stature Signup and view all the answers

Which karyotype corresponds with a common mosaic situation in males?

47, XXY Signup and view all the answers

What is a major misconception related to the XYY karyotype?

XYY has been inaccurately associated with aggression. Signup and view all the answers

Which of the following traits is commonly associated with XXX females?

Taller than average stature Signup and view all the answers

What typically occurs during meiosis in males with XYY karyotype?

Only one X chromosome pairs up Signup and view all the answers

What is the prognosis for individuals with an XXX chromosome arrangement in terms of intelligence and life expectancy?

Average intelligence and normal life expectancy Signup and view all the answers

What is the approximate percentage of conceptions that can be expected to terminate successfully up to 12 weeks of pregnancy?

90% Signup and view all the answers

Which technique allows for the identification of chromosomal abnormalities at a sensitivity level lower than 5 megabases?

Fluorescence in Situ Hybridization (FISH) Signup and view all the answers

What is the primary origin of the chromosomal abnormalities found in adult gametes?

Mutations during gametogenesis Signup and view all the answers

At what maternal age does the incidence of chromosomal abnormalities in prenatal diagnosis notably increase to between 7-8%?

40 years Signup and view all the answers

What is a distinct advantage of using molecular cytogenetics over classical cytogenetics?

Increased sensitivity to smaller chromosomal deletions Signup and view all the answers

What is the most commonly affected area in triploidy cases?

Central nervous system Signup and view all the answers

Which characteristic is most associated with cri du chat syndrome?

Cat-like cry Signup and view all the answers

Which chromosome is most commonly associated with cri du chat syndrome?

Chromosome 5 Signup and view all the answers

What is a significant outcome for individuals with chromosome 18 abnormalities?

Mosaicism or translocations Signup and view all the answers

What is the effect of triploidy on the fetus’s chance of survival?

Most triploid fetuses will not survive birth Signup and view all the answers

What is the role of genetic counseling?

To communicate genetic risks and familial connections Signup and view all the answers

Which of the following describes a common physical feature in cri du chat syndrome?

Heavy growth retardation Signup and view all the answers

What type of chromosomal alteration is primarily associated with mosaic triploidy?

Mosaicism of triploid cells Signup and view all the answers

Which feature is often observed in the placentas of triploidy cases?

Grapelike clusters of villi Signup and view all the answers

Which typical condition is associated with chromosome 18 abnormalities?

Microcephaly Signup and view all the answers

What is the primary purpose of the nuchal translucency test during pregnancy?

To estimate risk for chromosomal conditions Signup and view all the answers

Which combination of abnormalities detected through the triple test suggests a suspicion for trisomy 18?

Decreased levels of all three molecules Signup and view all the answers

In which circumstance should invasive tests for prenatal cytogenetics be conducted?

If there is a family history of chromosomal abnormalities Signup and view all the answers

What unique advantage does preimplantation genetic diagnosis (PGD) provide?

It allows for screening before embryo implantation Signup and view all the answers

What is the main risk associated with chorionic villi sampling and amniocentesis?

False negatives and false positives Signup and view all the answers

What does the presence of the Y chromosome in oocytes indicate in relation to genetic conditions?

High risk for X-linked conditions in males Signup and view all the answers

Why is early amniocentesis preferred for certain tests conducted after week 14?

It has a faster result turnaround time Signup and view all the answers

What is a key characteristic of chorionic villi useful for karyotype analysis?

They can reproduce rapidly Signup and view all the answers

Which of the following statements regarding non-invasive tests is true?

They only calculate risks, not providing definitive diagnoses Signup and view all the answers

Which non-invasive test utilizes a blood sample from the mother?

Triple test Signup and view all the answers

How does the presence of lymphedema in newborns with Turner Syndrome reflect the underlying genetic abnormalities?

Lymphedema in newborns with Turner Syndrome is often due to disrupted lymphatic development, associated with atypical chromosomal arrangements affecting vascular growth. Signup and view all the answers

What significance does the SHOX gene hold in relation to the physical stature of females with Turner Syndrome?

The SHOX gene, being present on the sex chromosomes and escaping X inactivation, results in reduced expression and hence contributes to the short stature characteristic of Turner Syndrome. Signup and view all the answers

In what ways do the variations in clinical manifestations of Turner Syndrome lead to diagnostic challenges?

The diverse symptoms, such as short stature, ovarian failure, and osteoporosis, create variability among patients that can mask or mimic other conditions, complicating accurate diagnosis. Signup and view all the answers

Discuss the implications of primary amenorrhea in females diagnosed with Turner Syndrome.

Primary amenorrhea indicates a lack of sexual development and infertility, representing a core symptom of Turner Syndrome that affects personal and psychological well-being. Signup and view all the answers

What role does somatic mosaicism play in the phenotypic expression of genetic disorders, particularly in Turner Syndrome?

Somatic mosaicism can result in a mix of normal and abnormal cells, influencing the severity and variety of symptoms in Turner Syndrome based on the distribution of affected cells. Signup and view all the answers

In Klinefelter syndrome, what genetic factor may contribute to increased height in affected males?

The presence of three copies of the SHOX gene may contribute to increased height in males with Klinefelter syndrome. Signup and view all the answers

What are common physical characteristics associated with Klinefelter syndrome?

Common characteristics include tall stature, gynecomastia, disproportionate limbs, and hypogonadism. Signup and view all the answers

How does the presence of PAR regions affect X chromosome inactivation?

PAR regions do not undergo X chromosome inactivation, allowing genes in these regions to be expressed from both X chromosomes. Signup and view all the answers

What misconception about the XYY karyotype was debunked by recent studies?

The misconception that individuals with XYY karyotype are predisposed to violent behavior has been deemed incorrect. Signup and view all the answers

What is the potential impact of having an additional X chromosome in XXX females?

Though they may experience some cycle irregularities, XXX females are typically fertile and phenotypically normal. Signup and view all the answers

Describe the significance of the SHOX gene in individuals with Turner Syndrome.

In Turner Syndrome, a single copy of the SHOX gene can lead to short stature. Signup and view all the answers

What chromosomal arrangement is described by the karyotype 46,XX with a translocation of the SRY gene?

This arrangement results in a phenotype that presents as a male due to the presence of the SRY gene. Signup and view all the answers

What is the typical appearance of placentas affected by mosaic triploidy?

The placenta typically shows scattered grapelike villi, resembling a hydatidiform mole. Signup and view all the answers

What are two primary systems affected by triploidy in fetuses?

The central nervous system and the skeletal system are predominantly affected. Signup and view all the answers

What genetic alteration is responsible for cri du chat syndrome?

Cri du chat syndrome is caused by a deletion on the short arm of chromosome 5 (5p). Signup and view all the answers

How does triploidy generally affect the fetus's overall chance of survival?

Most fetuses with triploidy do not survive birth; however, mosaic cases may have improved prognoses. Signup and view all the answers

What does genetic counseling aim to achieve?

Genetic counseling aims to inform patients about genetic defects and assess the reproductive risk for families. Signup and view all the answers

What are two common physical features of individuals with cri du chat syndrome?

Common features include a cat-like cry and microcephaly, often accompanied by roundish facial features. Signup and view all the answers

What are some common chromosomal abnormalities associated with chromosome 18?

Chromosome 18 abnormalities include deletions and ring chromosome formations. Signup and view all the answers

Why is early identification of genetic disorders important in genetic counseling?

Early identification aids in assessing risks for family members and planning for potential medical care. Signup and view all the answers

What is the significance of the 'cat cry' symptom in cri du chat syndrome?

The 'cat cry' is significant as it results from hypoplasia of the laryngeal cartilages and marks early development. Signup and view all the answers

What are two examples of invasive tests that can lead to a definitive prenatal diagnosis?

Chorionic villi sampling and amniocentesis. Signup and view all the answers

How does the triple test evaluate the risk of neural tube defects?

By measuring the levels of AFP, Beta hCG, and uE in a blood sample from the mother. Signup and view all the answers

What is the main advantage of preimplantation genetic diagnosis (PGD) in assisted reproductive technology?

It allows for the identification of genetic disorders before embryo implantation. Signup and view all the answers

What could an increased level of Beta hCG alongside a decreased presence of AFP and uE indicate?

A potential suspicion for trisomy 21 (Down syndrome). Signup and view all the answers

Why should invasive prenatal tests like chorionic villi sampling only be conducted under serious risk indications?

Due to the associated risks of false negatives, false positives, and potential miscarriage. Signup and view all the answers

In the context of prenatal testing, what does the term 'nuchal translucency' refer to?

It refers to the measurement of fluid at the back of the fetus's neck via ultrasound. Signup and view all the answers

What is necessary for conducting prenatal cytogenetic analysis using amniocentesis?

A sample of amniotic fluid that contains fetal cells for karyotype analysis. Signup and view all the answers

What does the analysis of chorionic villi allow researchers to do more rapidly than amniocentesis?

It enables quicker karyotype analysis since the sample is enriched with actively dividing fetal cells. Signup and view all the answers

What ethical consideration does preimplantation genetic diagnosis (PGD) help to mitigate?

It reduces the ethical debate surrounding selective pregnancy terminations based on genetic findings. Signup and view all the answers

Study Notes

Somatic Terminal Mosaicism and Turner Syndrome

Low level of somatic terminal mosaicism observed in humans; typically less than 2% of cells exhibit this phenomenon.
Menopause can occur before menarche in Turner Syndrome, resulting in incomplete sexual development.
Ovaries in Turner patients are elongated, filled with stromal tissue, and lack follicles, leading to oocyte apoptosis usually by age two.
Primary amenorrhea arises from ovarian failure in these females, commonly associated with estrogen deficiency.
In rare instances (less than 10%), puberty may occur, allowing for potential pregnancies, albeit with a high risk of fetal loss.

Turner Syndrome Phenotypes

Almost all affected individuals exhibit short stature and primary gonadal failure leading to infertility.
Additional symptoms may include osteoporosis in up to 50% of patients, cubitus valgus, carbohydrate intolerance, and high blood pressure.
Lymphedema presenting as puffiness in hands and feet often observed in newborns.
Short stature linked to the SHOX gene (Short Stature Homeobox), which is located in the pseudoautosomal regions (PAR) of sex chromosomes, escaping X chromosome inactivation.
Individuals with Turner Syndrome express only one copy of the SHOX gene, impacting growth.

Klinefelter Syndrome

Characterized by an extra X chromosome (XXY), typically presenting with tall stature, gynecomastia, limb disproportion, and hypogonadism.
A significant proportion (up to 50%) of Klinefelter pregnancies result in live births despite embryonic development issues.
Males with this syndrome have three copies of the SHOX gene, contributing to increased height.
Low testosterone levels lead to azoospermia and complete infertility, but intelligence and life expectancy remains normal.

Chromosomal Variants of Klinefelter Syndrome

Variants include XXYY (1 in 17,000), XXXY (1 in 50,000), and rare XXXX (1 in 85,000 to 100,000).
46,XX individuals with a translocation of Y chromosome material can appear male phenotypically if they possess the SRY gene.

Non-Disease Associated Chromosomal Conditions

XYY males are typically fertile and may be taller due to three copies of the SHOX gene, without associated pathology.
Triple X syndrome (XXX) results in phenotypically normal females who are usually fertile; this condition occurs in roughly 1 in 1,200 females.

Triploidy and Associated Conditions

Triploidy (69 chromosomes) can form from double fertilization, leading to severe developmental issues and high miscarriages in pregnancies.
Characteristic placental appearance relates to hydatidiform mole; many fetuses will not survive due to severe malformations, primarily affecting the central nervous system and skeletal system.

Cri du Chat Syndrome

Results from a deletion on chromosome 5p, leading to distinct features such as a cat-like cry, delayed psychomotor development, and possible congenital heart defects.
Life expectancy is generally long, but patients often experience growth retardation and mental disabilities.

Chromosome 18 Abnormalities

Various structural abnormalities on chromosome 18 lead to significant developmental issues, including deletions and ring chromosome formations.
Affected individuals may present differing syndromes affecting overall health and developmental outcomes.

Genetic Counseling Overview

Aims to identify genetic disorders in individuals and families, assess reproductive risks, and provide clear communication without being directive.
Counseling can address the likelihood of passing genetic conditions to offspring and includes risk assessment of carrier statuses.
Non-invasive prenatal testing options include nuchal translucency and triple tests, while invasive methods like chorionic villi sampling and amniocentesis can definitively diagnose genetic abnormalities.

In Vitro Fertilization and Preimplantation Genetic Diagnosis (PGD)

PGD allows for the early assessment of embryos for genetic conditions, effectively preventing potential complications from inherited defects.
Requires in vitro fertilization to obtain embryos for evaluation, often used when there is a known risk of genetic disorders in family history.### Single Cell Techniques
Only a few molecular techniques like PCR and sequencing can analyze a single cell.
Investigation of the Y chromosome presence in oocytes is critical due to the recurrence of serious X-linked conditions in newborn males.

Preimplantation Diagnosis

Molecular probes specific to chromosome regions are used for preimplantation genetic diagnosis.
Probes can render certain chromosome areas fluorescent and are applicable to interphase nuclei or metaphases.

Conception and Abortion Rates

Approximately 25% of conceptions successfully lead to birth.
Early-stage abortions account for about 20% before implantation.
Abortion rates decrease to 42% by the 7th week, then to 10% between weeks 7 and 12, and to 3% after the 12th week.

Chromosomal Abnormalities and Maternal Age

Frequency of chromosomal abnormalities detected in prenatal diagnosis correlates with maternal age.
Incidence of abnormalities at age 35 is higher and increases to 2.5-3.5% at age 40, and 7-8% at age 45.
Germ cells possess chromosomal abnormalities due to mutations during gametogenesis.

Abnormalities in Gametes

Approximately 10% of sperm from healthy males have chromosomal abnormalities; about 50% of these are numeric.
Around 25% of oocytes may have chromosomal abnormalities, predominantly aneuploidy, resulting in numerical alterations.

Molecular Cytogenetics

Molecular cytogenetics combines DNA analysis with chromosome study for targeted analysis of chromosomal regions.
Allows for the identification of rearrangements of several hundred kilobases, enhancing sensitivity beyond classical cytogenetics.

Fluorescence in Situ Hybridization (FISH)

FISH is a molecular cytogenetic technique that hybridizes DNA to study chromosomal abnormalities, particularly useful for identifying microdeletions.
Techniques like PRINS, PCR in situ, and CGH are also utilized in this field.
Probes can target specific chromosome regions, including centromeric, telomeric, or locus-specific probes.

Chromosome Territories

FISH allows visualization of discrete chromosome territories in interphase nuclei, facilitating anomaly diagnosis including numerical alterations and aneuploidies.
Example probes can identify specific chromosomes such as Y chromosome and chromosome 21 in Down syndrome diagnostics.

Advantages and Disadvantages of FISH

Advantages include fast identification of microdeletions and the capacity to analyze nuclei without mitosis.
Disadvantages involve high costs compared to classical cytogenetics and potential for incomplete diagnoses.

Comparative Genomic Hybridization (CGH)

CGH analyzes the entire genome, identifying deletions or duplications by comparing a patient's genome to a reference genome.
This technique is vital for detecting genetic imbalances based on hybridization results.
Visual representation of hybridization results supports diagnosis of genomic duplications or deletions based on color discrepancies.

Diagnosing Chromosomal Alterations

Array CGH utilizes small probes immobilized on a microchip to detect complementary regions of the patient genome.
Can differentiate between balanced and unbalanced translocations while supporting diagnosis of deletions and duplications effectively.