Cytogenetic Disorders Flashcards
What is the liveborn incidence with 22q11.2 micro deletions?
1/4000
What is the liveborn incidence with 22q11.2 micro duplication?
Much rarer than 22q11.2 micro deletions.
What is CAT-EYE syndrome?
4 copies of 22q11.2 locus.
What is the birth incidence of Crime du Chat?
1/15,000 live births
What is the cytogenetic locus responsible for Cri du Chat?
5p DELETION. -> 5p15 is the critical region for Cri du Chat
What are the facial features of Cri du Chat?
Microcephaly Hypertelorism Epicanthal folds Low set ears Micro/retrognathia
What syndrome and molecular variant does this baby have?
CRI DU CHAT
5p-
Due to loss of 5p15 critical region. Note hypertelorism, epicanthal folds and microcephaly. Retrognathia also common.
What parental allele is lost in Prader Wili?
Loss of paternal allele.
Remember because Prader Wili starts with a P for paternal
What is the mnemonic for Prader Wili allele loss?
P in Prader Wili is for loss of PATERNAL allele expression
What parental allele is lost in Angelman syndrome?
The Maternal allele is lost in Angelman.
Remember because these kids are sweet and a mother would love to have them
What is the cytogenetic cause of XYY syndrome?
XYY syndrome can ONLY be caused by PATERNAL meisosis II nondisjunction.
When do female cells engage X-inactivation?
Female cells inactivate one of the X chromosomes at RANDOM very early in development (before implantation).
What is the 90 percentile range for normal female X-inactivation skewing?
Normal is 50% of cells have X-inactivated one parents X-chr in a woman.
90% of women will have X-inactivation ratios of 1/4 to 3/4.
IE this means 25%-75% of her cells are skewed. Less than 10% of women have X-skewing where greater than 75% one way or the other.
What are the three situations where X-inactivation is NOT random
1) Structurally abnormal X -> The abnormal X is inactivated.
2) Balanced X;autosome: The normal X is inactivated
3) Unbalanced X;autosome: The abnormal X is inactivated
What is the general rule for non-random X-inactivation?
Maintain gene dosage, so shut down what X chr that will keep things normal.
What are the incidence of 47,XXY?
Klinefelters Disorder affects 1/600 males
What is the clinical features of 47,XXY
Tall male with gonadal hypoplasia and slim shoulders. Often with gynecomastia (male breast development).
What is the IQ impact of 47,XXY
Can have normal IQ (we’ve met one) but also possible for verbal IQ to low
What is the behavorial impact of 47, XXY?
Klinefelters have no major behavorial deficits
What is the impact of 47,XXY on fertility?
Infertile male (often first clinically observed for infertility workup).
Azoospermia and hypogonadism.
What is the incidence of 47,XYY
1/1000 male births
What is the clinical presentation of 47,XYY?
Tall but otherwise normal male appearance
What is the IQ impact of 47,XYY?
Reduced verbal IQ, language and reading difficulties
What is the behavioral impact of 47,XYY?
A subset of these patients will have behavioral problems (likely affiliated with lower IQ).
What is the incidence of 47,XXX (Trisomy X)
1/1000 female births will have Trisomy X
What is the clinical presentation of Trisomy X?
Hypotonia with delayed developmental milestones. Taller than normal. Learn+Language issues
What is the IQ of Trisomy X?
Normal to low
Behavioral impact of 47,XXX
Typically normal
What is the fertility of Trisomy X?
Reduced fertility in some. Premature ovarian failure in some (ovaries fail before 40).
What is the impact of variant Klinefelters?
More than one X. Any X beyong 47,XXY leads to more severe phenotype prediction.
What is the impact of variant Trisomy X?
Additional X chromosomes will result in a more severe phenotype
What is the incidence 45,X?
Turner syndrome occurs in 1/2500-1/4000 female births.
What is the spontaneous abortion rate of 45,X fetuses?
99% of all 45,X (Turner) fetuses will abort spontaneously.
What is the common clinical presentation of Turners syndrome?
Short
Webbed neck
Lymphedmia
Risk for cardiac abnormalities
What is the diagnosis and molecular cause of this patients disorder?
45,X Turner syndrome.
Note webbed neck with short stature. This child is a survivor. 99% of other babies with this genotype will spontaneously abort.
What does DSD stand for?
Disorder of sexual development
What is gonadal dysgenesis?
Progressive loss of the germ cells followed by failure to correctly develop 2’ sexual characteristics.
What is the molecular yield of chromosomal microarray testing in patients with intellectual disability?
Up to a 12-15% of intellectual disability patients have a pathogenic CNV detectable by chromosomal microarray.
