Chapter 17: Chromosome Disorders Flashcards
Down Syndrome
Trisomy 21
First Described in 1866 by John Langdon Down
Most common trisomy in human live births
Chromosome findings: Pure Trisomy 95%, translocation 4%, mosaicism 1%
In the pure trisomy cases, maternal chromosome non-disjunctions account of about 90%
Phenotype: Upward sloping plaperbal fissure, protruding tongue
The syndrome is correlated to an individual advanced maternal age
Trisomy 13
Patau Syndrome
Severe conditions and poor prognosis
Sever cleft lip and palate. Heart defects in 90% cases
Incidence:1/5000 newborn babies
Most infants die during the first few days or weeks of life
Correlation between the advance maternal age and the incidence
Trisomy 18
Edward Syndrome The incidence is 1 in 5000 live birth. The incidence at the conception is much higher, but 95% of trisomy 18 fetuses are aborted Sever malformation of the heart Prominent occiput(back of the head) Characteristics fists clench
Turner Syndrome
Incidence: 1/5000 to 1/10,000
Puffy Extremities(edema)
Webbed neck, low hair line, widely spaced nipples
Monosomy X chromosome (45,X; 50%), or mosaicism (45,X/46,XX; 30%-40%)
Occurs only in females
Infertile due to lack of ovaries
Missing paternal X chromosome
Klinefelter Syndrome
Incidence: 1/1000 male live birth
First discovered in 1959; 47,XXY
The syndrome is characterized by moderate learning difficulties, enlargement of the breasts, and infertility (100%)
An increased incidence of carcinoma of the breasts in the adult life
The extra X chromosome is maternal in origin in about 50% of cases
A higher incidence of the disease is associated with advanced maternal age
Treatment includes male hormone and mastectomy of the enlarged breast to prevent development of cancer
48,XXXY
Fragile X Syndrome
First described by Martin and Bell in the 1940s.
Incidence: 1/5000 males
4-8% of all males with learning difficulties
The X chromosome abnormality was discovered in 1969
The fragile site is the gap between the end of the X chromosome and the rest of the long arm
“CGG” expansion was discovered in 1991
Moderate to severe learning difficulties
Autistic behavior
The mutation FRAXA gene is the triplet repeat expansion
Cri-du-Chat
5p deletion Growth deficiency Cat-like cry in infancy minor heart defects Down-slanting, wide set eyes Single, transverse palmar crease Severe mental retardation
Wolf-Hirschhorn Syndrome
4p deletion
Growth deficiency
Small head
Wide-set eyes
“Greek warrior helmet” appearance of face
Severe mental retardation
Phenotype only requires deletion of extreme distal end of 4p
Microdeletion Syndromes
Deletion 22q11 Syndrome
William Syndrome
Angelman Syndrome
Prader-Willi Syndrome
Deletion 22q11 Syndrome
Also Called Velocardiofacial Syndrome and DiGeorge Syndrome
Most common chromosome deletion syndrome with incidence 1 in 4000 live births
The deletion is about 3Mb long and this region contains many genes. The deletion is caused by low copy repeats (LCR)
TBX1 gene is considered to be responsible to the heart and thymus development during embryogenesis
The commercial FISH probe used is called LSI TUPLE1
William Syndrome
Prominent lips Small eyes Heart defects Very friendly toward strangers Submicroscopic interstitial deletion of 7q11.23
Angelman Syndrome
Seizures
Ataxic, “puppet-like” gait
Spontaneous, inappropriate bursts of laughter
Deletion of maternal chromosome 15q11.2 (85%), uniparental disomy of parental chromosome 15 (5%), or mutation of UBE3A (10%)
Prader-Willi Syndrome
Hypotonia as an infant
Small hands
Genital abnormalities in males
Obesity beginning after infancy
Skin may be scarred from excessive picking of insect bites or other sores
Deletion of parental chromosome 15q11.2 (70-85%), or uniparental disomy of maternal chromosome 15
Uniparental disomy
When an individual inherits both chromosomes of a homologous pair from one parent
Imprinting
The phenomena of a gene or region of a chromosome showing different expression depending on the parent of origin
