Chromosomal Abnormalities

How many chromosomes are in a normal human cell?

46 chromosomes

What is the term for a cell that contains a multiple of 23 chromosomes?

Euploid cell

What is an aneuploid cell?

A cell that contains missing or additional individual chromosomes (not a multiple of 23)

What are the two main types of aneuploidies?

Autosomal aneuploidies

Sex chromosome

autosomal aneuploidy

condition where there is a missing or extra chromosome in the autosomes (chromosomes 1-22) e.g. trisomy 21 (Down syndrome)

What is sex chromosome aneuploidy?

condition where there is a missing or extra sex chromosome (X or Y), such as Turner syndrome (45,X) or Klinefelter syndrome (47,XXY)

What are the two types of autosomal aneuploidies?

Monosomy

Trisomy

What is monosomy?

A type of aneuploidy where a chromosome is missing (45 chromosomes instead of 46) usually lethal in autosomes

What is trisomy?

type of aneuploidy where there is an extra chromosome (47 chromosomes instead of 46), commonly seen in live births (trisomy 21 - Down syndrome)

Are autosomal monosomies compatible with survival to term?

No they are nearly always incompatible with survival to term

Which type of autosomal aneuploidy is more commonly seen in live births?

trisomies

What is the difference between an excess and a deficit of genetic material?

An excess of genetic material (e.g. trisomy) is generally better tolerated than a deficit of genetic material (e.g. monosomy)

What is non-disjunction?

The failure of chromosomes to disjoin normally during meiosis or mitosis, leading to aneuploidy

how does maternal age affect the prevalence of Down syndrome?

The risk increases with maternal age:

less than 1/1000 for mothers under 30

1/400 at age 35

1/100 at age 40

1/25 at age 45

How does maternal age influence the likelihood of spontaneous abortion in trisomic pregnancies?

are less likely to be spontaneously aborted in older women

What is the role of prenatal diagnosis in trisomies?

helps identify trisomies early, allowing for informed decision-making and management

What is the incidence of Down syndrome (trisomy 21)?

1 in every 700 to 1000 live births

What is a characteristic appearance of individuals with Down syndrome?

They may have a depressed nasal root, upslanting palpebral fissures, small and sometimes overfolded ears, and a flattened maxillary and malar region.

Q: What physical features are common in individuals with Down syndrome?

A short neck, broad and short hands and feet, and a single palmar crease in 50% of patients.

What is a highly consistent feature in individuals with Down syndrome that can aid in diagnosis?

Decreased muscle tone (hypotonia)

What percentage of infants with Down syndrome develop an obstruction of the duodenum or atresia of the esophagus, duodenum, or anus?

About 3% of infants with Down syndrome.

What is the increased risk of developing leukemia in individuals with Down syndrome?

15 to 20 times higher than in the general population.

What is the most significant medical problem in individuals with Down syndrome?

Approximately 40% of individuals with Down syndrome are born with structural heart defects

Intellectual disability can be present in individuals with Down syndrome. T/F

True

What is the most important cause of early mortality in individuals with Down syndrome?

Congenital heart defects are the most important single cause of early mortality (10-50 years)

What is the prevalence of mosaicism in Down syndrome, and how does it affect the clinical presentation?

occurs in 2-4% of Down syndrome patients and typically results in milder clinical expression.

What chromosomal abnormality is associated with Down syndrome?

caused by a translocation, typically t(14;21).

In what percentage of Down syndrome cases is the extra chromosome 21 contributed by the mother?

contributed by the mother in 90% to 95% of cases

What is mosaicism?

A condition where an individual has two or more genetically different cell lines, often resulting in varying clinical effects.

What is the prevalence of Trisomy 18 (Edward syndrome)?

1 in 6,000 live births.

What percentage of Trisomy 18 conceptions survive to term?

Fewer than 5% of Trisomy 18 conceptions survive to term

What are some common physical features of individuals with Trisomy 18?

Small ears with unraveled helices, a small mouth that is hard to open, and a short sternum

What is the most common medical issue in children with Trisomy 18?

Congenital heart defects, which occur in 90% of children

What are some other common conditions associated with Trisomy 18?

Omphalocele (protrusion of the bowel into the umbilical cord)

radial aplasia (missing radius bone)

diaphragmatic hernia

occasionally, spina bifida

What is the prevalence of Trisomy 13 (Patau syndrome)?

1 in every 10,000 births

What are some common physical features of individuals with Trisomy 13?

Orofacial clefts, microphthalmia (small, abnormally formed eyes), and postaxial polydactyly (extra fingers or toes)

What other malformations are often seen in individuals with Trisomy 13?

of the central nervous system, heart defects, renal abnormalities, and cutis aplasia (a defect of the skin of the scalp on the posterior occiput).

What is the survival rate for infants with Trisomy 13?

95% of live-born infants with Trisomy 13 die during the first year of life

What percentage of Trisomy 13 conceptions are spontaneously lost during pregnancy?

95% or more of Trisomy 13 conceptions are spontaneously lost during pregnancy

What are some common features of Turner syndrome?

Short stature, sexual infantilism, ovarian dysgenesis, and a pattern of major and minor malformations.

What is the characteristic facial appearance in individuals with Turner syndrome?

A triangle-shaped face

Why do individuals with Turner syndrome typically not develop secondary sexual characteristics?

They lack normal ovaries, and most women with this condition are infertile.

What is the most common karyotype in individuals with Turner syndrome?

About 50% of individuals with Turner syndrome have a 45,X karyotype.

What types of mosaicism are commonly seen in Turner syndrome?

30% to 40% of individuals with Turner syndrome have mosaicism, most commonly 45,X/46,XX and less commonly 45,X/46,XY.

What percentage of individuals with Turner syndrome have structural abnormalities involving the X chromosome?

About 10% to 20% of individuals with Turner syndrome have structural X chromosome abnormalities, often involving a deletion of some or all of Xp.

What is a common feature of Klinefelter syndrome (47,XXY) in males?

Small testes and sterility due to atrophy of the seminiferous tubules.

What are some hormonal and physical features associated with Klinefelter syndrome?

low testosterone levels in adolescents and adults

gynecomastia (development of breast tissue)

reduced muscle mass

What cognitive issues are commonly seen in individuals with Klinefelter syndrome?

A predisposition for learning disabilities and a reduction in verbal IQ.

What role does mosaicism play in Klinefelter syndrome?

occurs in about 15% of patients, increases the likelihood of viable sperm production.

What other karyotypes have been reported in individuals with Klinefelter syndrome?

Individuals with 48,XXXY and 49,XXXXY karyotypes have also been reported.

What is polyploidy?

presence of a complete set of extra chromosomes in a cell.

What are the two types of polyploidy mentioned?

Triploidy (69 chromosomes) and tetraploidy (92 chromosomes).

What is the prevalence of triploidy in live births?

1 in 10,000 live births, but it accounts for about 15% of chromosome abnormalities occurring at conception

What happens to most triploid conceptions?

The vast majority of triploid conceptions are spontaneously aborted.

What happens to triploid fetuses that survive to term?

Triploid fetuses that survive to term typically die shortly after birth.

What is the most common cause of triploidy?

fertilization of an egg by two sperm (dispermy).

What is another cause of triploidy?

caused by the fusion of an ovum and a polar body, each containing 23 chromosomes, followed by fertilization by a sperm cell

How rare is tetraploidy compared to triploidy?

much rarer than triploidy, both at conception and among live births. It has been recorded in only a few live births, and those infants survived for only a short period.

What is one cause of tetraploidy?

mitotic failure in the early embryo, where all duplicated chromosomes migrate to one of the two daughter cells.

How else can tetraploidy occur?

from the fusion of two diploid zygotes.

What is the leading known cause of pregnancy loss?

Chromosome abnormalities are the leading known cause of pregnancy loss.

What percentage of conceptions are estimated to have a chromosome abnormality?

10% to 20% of conceptions have a chromosome abnormality.

What percentage of conceptions with chromosome abnormalities are lost before term?

95% of conceptions with chromosome abnormalities are lost before term.

What do karyotype studies of miscarriages show about the types of chromosome abnormalities?

About 50% of chromosome abnormalities are trisomies

20% are monosomies

and 15% are triploids

The remainder consists of tetraploids and structural abnormalities.

Which chromosome abnormality is common at conception but seldom survives to term?

Trisomy 16 is common at conception but seldom or never survives to term.

What does an abnormality of chromosome structure involve?

An abnormality of chromosome structure involves the alteration of the structure of a chromosome.

What are some types of chromosome rearrangements?

include translocations, deletions, duplications, inversions, insertions, ring chromosomes, and isochromosomes.

What are the types of translocations?

types of translocations are reciprocal, non-reciprocal, and Robertsonian.

What is a chromosome deletion?

A chromosome deletion involves the loss of a portion of the chromosome.

What is chromosome duplication?

Chromosome duplication occurs when a portion of the chromosome is duplicated, resulting in extra genetic material.

What is a chromosome inversion?

involves the rearrangement of a chromosome segment in the reverse order.

What is chromosome insertion?

when a segment of one chromosome is inserted into another chromosome.

What is a ring chromosome?

forms when the ends of a chromosome fuse, creating a circular structure.

What is an isochromosome?

chromosome in which one arm is lost, and the remaining arm is duplicated.

What are the two types of chromosome rearrangements?

two types are unbalanced and balanced rearrangements.

What is an unbalanced chromosome rearrangement?

causes a gain or loss of chromosomal material, often leading to disease.

What is a balanced chromosome rearrangement?

does not produce a loss or gain of chromosome material.

What causes homologous chromosomes to line up improperly during meiosis?

occur due to unequal crossover between homologous chromosomes.

What happens during the pairing or synapsis of homologous regions in chromosomes?

one or both chromosomes may form a loop and twist to allow the proper alignment of these regions.

What is a chromosome deletion?

occurs when a portion of the chromosome is missing or deleted.

What are the two types of deletions?

large deletions and small deletions

What is a terminal deletion?

type of deletion where a single break leads to the loss of the chromosome's tip.

What is an interstitial deletion?

occurs when two breaks in the chromosome happen, and the material between the breaks is lost.

What happens if a deletion includes the centromere?

the chromosome will not be segregated properly during mitosis or meiosis.

What is a characteristic feature of Cri-du-chat syndrome?

The distinctive cry of the child

What chromosome abnormality causes Cri-du-chat syndrome?

by a deletion of the distal short arm of chromosome 5 (46,XY, del(5p)).

What are common symptoms of Cri-du-chat syndrome?

intellectual disability, microcephaly, and a characteristic, though not distinctive, facial appearance.

Can individuals with Cri-du-chat syndrome survive to adulthood?

can survive to adulthood if serious congenital defects are not present.

What are microdeletion syndromes?

involve deletions of genetic material smaller than 5Mb.

What is Williams syndrome?

microdeletion syndrome that causes intellectual disability, supravalvular aortic stenosis, multiple peripheral pulmonary artery stenoses, and characteristic facial features.

What gene is associated with the aortic wall in Williams syndrome?

The ELN gene, which encodes elastin, a component of the aortic wall

Which gene in Williams syndrome is involved in visual-spatial cognition defects?

The LIMK1 gene, a brain-expressed kinase

What is a chromosome inversion?

occurs when a portion of the chromosome breaks off, turns upside down, and reattaches, resulting in inverted genetic material.

What is a paracentric inversion?

when the centromere is not included in the inversion.

What is a pericentric inversion?

is when the centromere is included in the inversion.

How does inversion affect the order of genes?

changes the order of the genes on the chromosome.

Why is the chromosomal position important for some genes?

Some genes are regulated in a way that depends on their chromosomal position, so inversion can affect their expression.

How can an inversion affect a gene?

can break a gene into two parts, potentially disrupting its function.

What is a chromosome duplication?

occurs when a segment of the chromosome is duplicated, resulting in an extra copy of that segment.

What is one possible cause of chromosome duplication?

can be caused by unequal crossover during meiosis.