81 Cytogenetics Flashcards
Cell whose chromosomes are an exact multiple of 23
Euploid
Euploid cells with more than the diploid number of 46
Polypoid
Polypoid conceptions are usually not viable, but the presence of ____ with a _____ can allow survival.
Presence of mosaicism with a karyotypically normal line
Abnormality defined as the presence of 2 or more cell lines in a single individual
Mosaicism
Cells with 3 haploid sets of chromosomes and are only viable in a mosaic form
Triploid
The phenotype of a triploid conception depends on the origin of the extra chromosome set. If the extra set is of paternal origin, it results in a _____. But triploid conceptions that have an extra se of maternal chromosomes results in ____.
Paternal - partial H mole with poor embryonic development.
Maternal - severe embryonic retardation with a small fibrotic placenta
Most common and clinically significant type of human chromosome abnormality
Aneuploidy
Aneuploidy occurs in at least ___% of all clinically recognized prenancies
3-4%
Abnormal cells that do not contain a multiple of haploid number of chromosomes
Aneuploid cells
Occur when only 1, instead of the normal 2, of a given chromosome is present in an otherwise diploid cell.
Monosomies
In humans, most autosomal monosomies appear to be lethal early in development, and survival is possible in ____ or by means of ____.
Mosaic forms or chromosome rescue
An exception to the rule of monosomies
Turner syndrome
Monosomy (45,X)
Most common cause of aneuploidy
Nondisjunction
Failure of chromosomes to disjoin normally during meiosis
Nondisjunction
Characterized by the presence of 3 chromosomes, instead of the normal 2, of any particular chromosome.
Trisomy
Most common form of aneuploidy
Trisomy
Technique that can be used for rapid diagnosis in the prenatal detection of common fetal aneuploidies
FISH
The most common type of trisomy in liveborn infants
Trisomy 21
The occurence of trisomy 21 and other trisomies increases with ____
Advanced maternal age ≥35 years old
Most common genetic etiology of moderate intellectual disability
Trisomy 21
The incidence of down syndrome in live births
1 in 733
Is sterility affected in down syndrome?
Yes, most males are sterile
Females with down syndrome have been able to reproduce, with a ____% chance of having trisomy 21 pregnancies
50%
Developmental delay in down syndrome
Universal
Area of development spared in down syndrome
Social
The life expectancy for children with Down syndrome
50-55 years old
Accounted for 60% of all cancers in people with down syndrome and 97% of all cancers in children with down syndrome
Leukemias
4 maternal tests used to screen for Down syndrome
BHCG, unconjugated estriol, inhibin, alpha fetoprotein
Time to screen for down syndrome
Congenital heart disease
Birth
Time to screen for down syndrome
Strabismus, cataracts, nystagmus
Birth or by 6 months
Check vision annually
Time to screen for down syndrome
Hearing impairment or loss
Birth or by 3 mos
Check hearing q6 mo up to 3 years if typmanic membrane not visualized; annually thereafter
Time to screen for down syndrome
Constipation
Birth
Time to screen for down syndrome
Celiac disease
At 2 years or with symptoms
Time to screen for down syndrome
Hematologic disease
Birth and in adolescence
Time to screen for down syndrome
Hypothyroidism
Birth, repeat at 6-12 months old and annually
Time to screen for down syndrome
Obstructive sleep apnea
1 yr and at each visit
Time to screen for down syndrome
Atlantoaxial subluxation or instability
At each visit by history and PE
Radiographs at 3-5 or when planning to participate in contact sports
Radiographs when symtpomatic
The origin of the supernumerary chromosome 21 is maternal/paternal in 97% as a result in errors in ___.
maternal errors in meiosis I
The majority of translocations in down syndrome are fusions at the centromere between chromosomes ____
13, 14, 15, 21 and 22
Most common form of chromosomal translocation in Down Syndrome
Robertsonian translocation
Translocation (21;21) carriers have ___% recurrence risk for a chromosomally abnormal child
100%
Other Robertsonian translocations such as t(14;21) have a __% recurrence risk when transmitted by females
5-7%
Most commonly observed autosomal aneuploidy in spontaneous abortion
Trisomy 16
Most common chromosome abnormalities seen in liveborn infants, children and adults
Sex chromosome abnormalities
Characterized by complete or partial monosomy of the X chromosome and defined by a combination of phenotypic features
Turner syndrome
Is maternal age a predisposing factor for children with 45,X?
No
Turner syndrome occurs in approximately 1 in ____ female live births
5000
It has been estimated that ____% of 45,X conceptions are miscarried
95-99%
Common congenital defects associated with Turner syndrome
Structural renal anomalies (60%)
Congenital heart defects (40%)
Most common heart defects associated with Turner syndrome
Bicuspid aortic valves
Coarctation of the aorta
Aortic stenosis
Mitral valve prolapse
Intelligence of patients with Turner Syndrome
Normal
Endocrinologic care for patients with Turner syndrome
Pubertal induction
Treatment with growth hormone and oxandrolone
Patients with ____ can have Turner syndrome, although this form of mosaicism can also be associated with male pseudohermaphroditism, male or female genitalia in association with mixed gonadal dysgenesis or a normal male phenotype
45,X/46,XY mosaicism
Phenotypic females with 45,X/46,XY mosaicism have a 15-30% risk of developing _____
Gonadoblastoma
The APP has recommended the use of ____ to look for Y-chromosome mosaicism in all 45,X patients.
FISH analysis
If Y chromosome maternal is identified in 45,X patients, _____ is recommended
Laparoscopic gonadectomy
Noonan syndrome:
Autosomal dominant or recessive?
Autosomal dominant
Most commonly involved gene in Noonan Syndrome
PTPN11 (50%)
In contrast to Turner syndrome, Noonan syndrome affects ___ sexes, has a different pattern of congenital heart disease, typically involving _____.
Both
Right-sided lesions
Most common cause of hypogonadism and infertility in males
Klinefelter syndrome
Most common sex chromosome aneuploidy in humans
Klinefelter syndrome
In klinefelter syndrome, the more greater the aneuploidy, the more severe the ___ and ____
Mental mpairment and dysmorphism
Effect of klinefelter syndrome on puberty
Occurs at the normal age but testes are small, late secondary sex characteristics
____% of patients with klinefelter syndrome develop Gynecomastia
50%
Patients with ____ have a better prognosis for testicular function in klinefelter syndrome
46,XY/47,XXY
Each additional X chromosome in klinefelter syndrome reduces the IQ by ____
10-15 points
Main domains affected in development of Klinefelter syndrome
Language skills and social domains
Regions of chromosomes that show a tendency for separation, breakage, or attenuation under particular growth conditions.
Fragile sites
Fragile X syndrome is on which site of the chromosome?
Distal long arm of chromosome Xq27.3
Jacobsen syndrome is associated with the deletion of the distal long arm of ____
Chromosome 11
Main clinical manifestations of fragile X syndrome
Intellectual disability Autistic behavior Macroorchidism Hyperextensible finger joints Characteristic facial features
In fragile X syndrome, the larger the triplet expansion, the more significant the ____.
Intellectual disability
Males with permutation triple repeat expansions have been found to have an adult, late onset progressive neurodegenerative disorder known as ____
fragile X-associated tremor/ataxia syndrome
Two common errors of cell division that may occur during meiosis or mitosis
Nondisjunction
Anaphase lag
Most commonly used banding and staining method in chromosome analysis
GTG banding
Largest chromosome
1
Smallest chromosome
22
Used to identify the presence, absence, or rearrangement of specific DNA segments and is performed with gene-or region-specific DNA probes
Fluorescence in situ hybridization (FISH)
Most common nondisjunction in aneuploidies
Maternal meiosis I
Diagnosis
Cleft lip, flexed fingers with postaxial polydactyly, ocular hypotelorism, bulbous nose, microcephaly, low set-malformed ears, holoprosencephaly, microphthalmia, hypoplastic or absent ribs, visceral and genital anomalies
Patau Syndrome
Diagnosis
LBW, closed fists with overlapping fingers, narrow hips, short sternum, rocker-bottom feet, microcephaly, prominent occiput, micrognathia, cardiac and renal malformations, intellectual disability
Edwards syndrome
Diagnosis
Long face; high, prominent forehead; wide, upturned nose, thick, everted lower lip, microretrognathia, low-set ears; high-arched, sometimes cleft, palate, osteoarticular anomalies common, deep plantar and palmar creases
Trisomy 8,
mosaicism
More common: Edwards or Patau?
Edwards
More lethal: Edwards or Patau?
Edwards - 88% die in 1st yr
Patau - 80% die by 1 st yr
