11-CHROMOSOME ABNORMALITIES

constitutional abonormalities

anomalies that are inborn and have been always present in the embryo

acquired or somatic abnormalities

developed due to exposures, habits, or malignancies

numerical anomalies

one or more chromosomes in excess or missing (aneuploidy/polyploidy)

structural anomalies

structural changes within the chromosome not necessarily accompanied by any numerical change

numerical anomalies

happens when the number of chromosome in a somatic cell is not 46

individual chromosome have extra, missing or rearranged genetic material

account for 50% of spontaneous abortions but only 0.65% of newborns are born with these abnormalities

polyploidy

presence of extra sets of chromosome

triploid

2/3 are because of fertilization of an oocyte by 2 sperms

other cases are because of diploid gamete

responsible for 17% spontaneous abortions

triploid (3N)

individual who has 3 sets or copies of chromosomes

aneuploidy

cells have a missing single chromosome or having an extra chromosome

literally translates as “not good set”

most spontaneous aborted

those born are more likely to have an extra chromosome (trisomy) or missing one (monosomy)

Nondisjuction

aneuploidy etiologies

meiotic error where chromosome pair does not separate at anaphase of either 1st or 2nd meiotic division

Anaphase lag

aneuploidy etiologies

result of delayed movement (lagging) during anaphase

chromosome in meiosis or a chromatid in mitosis that fails to migrate or connect to the pole of the spindle apparatus will be lost from the nucleus as division is completed

hypoloidy

missing chromosome

hyperloidy

extra chromosome

monosomy

2n-1

absence of one member of a pair of chromosome

nullisomy

2n-2

loss of both pairs of homologous chromosomes

trisomy

2n+1

chromosomal condition characterized by an additional chromosome

polysomy

>2n+1

aneuploidy - triple X syndrome

tall structure

delayed development of speech and language skills

hypotonia

curved pinky fingers (clinodactyly)

behavior and mental health problems

premature ovarian failure or ovary abnormalities

constipation or abdominal pains

aneuploidy - down syndrome or trisomy 21

most common autosomal aneuploid among liveborns

patients survive because Ch21 has the fewest genes

intelligence varies but developmental milestones come

common for babies born to elderly women

aneuploidy - edward’s syndrome or trisomy 18

triple copies of chromosome 18

arise from nondisjunction in meiosis II

most patient have great physical and intellectual disability

skills remain stuck at 6 months level

90% of patients die within the first month

aneuploidy - edward’s syndrome or trisomy 18

kidney malformation

structural heart disease

omphalocoele

esophageal astresia

cognitive delay

oddly clenched fist

rocker bottom foot

aneuploidy - patau syndrome or trisomy 13

triple copies of chromosome 13

not compatible with life

serious intellectual disability

great physical disability

most striking feature is the fusion of the developing eyes into one large-eye like structure in the center of the face

aneuploidy - trisomy 16

the most common trisomy in first trimester losses

diagnosis of a trisomy 16 conceptus will most likely result in a fetal loss in the first trimester

sex chromosomes aneuploidy

people with this have extra or missing sex chromosomes

turner (XO) syndrome

monosomy of the x chromosome

generally, a sporadic event and the paternal sex chromosome is the most likely one missing

short stature

webbing at back of neck

incomplete sexual development (infertile)

impaired hearing

1 in 2,500 female births

99% of affected fetuses die in utero

klinefelter’s (XXY) syndrome

karyotype 47, XXY

affects 1:500 males

most common genetic or chromosomal cause of male infertility

maybe identified as an incidental finding or may present with behavioral difficulties

incomplete sexual development

rudimentary testes and prostate

long limbs, large hands and feet

some breast tissue development

balanced

if they have the normal amount of genetic material

not usually any clinical significance for the patient, unless genes are disrupted, but may have consequence for offspring

unbalanced

if they have extra or missing dna sequences

due to gain or loss of normal complement of genetic material

enzyme

recognize and repair broken chromosome

joining 2 broken ends together

capping

capping

broken ends of a telomere

inversion

occurs when a portion of the chromosome has broken off turned upside down and reattached

the genetic material is inverted

no loss or gain of chromosomal material thus carries are normal

paracentric inversion

if the inverted segment is on the long or short arm and does not involve the centromere

inversion is on one side

pericentric inversion

breaks occur in both the short and long arms and the inverted segment contains the centromere

even the position of the centromere is moved

duplication

an extra chromosomal segment within the same homologous chromosome or another non-homologous chromosome

cross over between misaligned chromosome

often not inherited rather they arise de novo

charcot-marie-tooth-disease type 1A

may be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP 22) on chromosome 17

overexpression of PMP 22

high foot arches

weakness of leg muscles

decrease sensation of legs

deletion

refers to the loss of a segment of a chromosome

often not inherited rather they arise de novo

larger deletions increase the likelihood that there will be an associated phenotype

unequal crossing over between misaligned homologous chromosome or sister chromatids

cri-du-chat syndrome

deletion 5p-

cry of cat syndrome

ring

rare

formed when the 2 arms have fused together

likely caused by the deletion of genes in the telomere regions of affected chromosome and sticky chromosome ends fuse

genes can be lost or disrupted causing symptoms

ring chr 14 and ring chr 13

associated with mental retardation, dysmorphic facial features

ring chr 15

associated with mental retardation, dwarfism and microcephaly

ring chr 20 syndrome

associated with epilepsy

ring x chromosome

causes turner syndrome

translocation

a structural rearrangement involving 2 non-homologous chromosomes

two non-homologous chromosomes exchange segments

reciprocal translocation

when segments from 2 different chromosomes have been exchanged

translocation breakpoint interrupts a gene, there may be an associated phenotype

robertsonian translocation

a particular type of translocation

involves reciprocal transfer of the long arms of 2 of the acrocentric chromosome 13,14,15,21,22

acrocentric break at the centromere and their long arms fuse

translocation

increase risk of cancer

some create oncogenes or activate genes that promote uncontrolled cell division leading to cancer

isochromosome

rare condition where chromosome have identical short and long arms

formed when centromere divide along the incorrect plane during meiosis

these are formed when a chromosome has lost one of its arms and this arm is replaced with an exact copy of a chromosome segment including the centromere

seen in turner syndrome and tumor cells