Bocian Clinical Syndromes Flashcards
What is triploidy
69 chromosomes
Describe the chromosome constitution of triploidy
69,XXY - 60%
69, XXX - 35%
69, XYY - 5%
Describe the etiology of triploidy
Most (65%) due to dispermy
Many (25%) due to fertilization with a diploid sperm (mitotic failure during meiosis)
Some (10%) due to fertilization with a diploid egg (failure to shed a polar body)
Two types of Trisomy 21 genotype
47, XY, +21
47, XX, +21
Down Syndrome is names for?
Dr. Langdon Down
Symptoms of Down Syndrome
Intellectual disabilities, usually mild to moderate
Typical physical features of down syndrome (6)
- Up-slanting eyes
- Small ears
- Thin, down-turned lips
- Short, broad hands
- Single transverse palmar crease
- 5th finger—single crease or short middle phalanx (middle segment)
Describe the tone of Down Syndrome
Hypotonia (“low tone;” poor muscle tone; “floppiness”)
Down syndrome organ dysfunction?
Congenital heart disease (45%)
Lifespan for Down syndrome
Essentially normal lifespan if there is no serious heart disease or other complication
Three types of chromosome abnormality in Down Syndrome
Nondisjunction
Translocation
Mosaicism
Describe Down Syndrome Nondisjunction
Nondisjunction (3 separate copies of chromosome 21)
a) Most patients (95%) have trisomy due to nondisjunction
Describe Down Syndrome translocation
Relatively few patients (3%) have translocations; t(14;21) is the most common—half are inherited,
half are de novo (occur for the first time in the patient); must do parents’ karyotypes to determine recurrence risk
Describe Down Syndrome Mosaicism
Relatively few patients have mosaicism (2%)
Describe recurrence risk of Down Syndrome
Recurrence risk depends on the mechanism (i.e., nondisjunction vs. de novo translocation vs. inherited translocation) and, in cases of nondisjunction, on the mother’s age at the time of the affected baby’s birth
Trisomy 13 is called?
Patau syndrome
Genotype for Trisomy 13
47, XY, +13
47, XX, +13
Abnormalities of Trisomy 13
Multiple anomalies: cleft lip ± cleft palate, polydactyly (extra fingers or toes),
microphthalmia (small eyes), omphalocele, cardiac anomalies, renal anomalies, etc.
Intellectual level of Trisomy 13
Severe intellectual disabilities
Lifespan of Trisomy 13
Severely shortened lifespan (few reach past 6 months)
Recurrence risk of Trisomy 13
Recurrence risk depends on the mechanism (i.e., nondisjunction vs. de novo translocation vs. inherited translocation) and, in cases of nondisjunction, on the mother’s age at the time of the affected baby’s birth
Trisomy 18 is also called?
Edwards syndrome
Trisomy 18 genotype
47, XY, +18
47, XX, +18
Abnormalities of Trisomy 18
Clenched hand position and typical facial features
Intellectual level of Trisomy 18
Profound intellectual diability
Lifespan of Trisomy 18
Severely shortened lifespan, most die before 1 year
Recurrence risk of Trisomy 18
Recurrence risk depends on the mechanism (i.e., nondisjunction vs. de novo translocation vs. inherited translocation) and, in cases of nondisjunction, on the mother’s age at the time of the affected baby’s birth
Genotype of Turner syndrome
45,X
Gender of Turner syndrome
Occurs only in females
Phenotype of Turner syndrome
Physically and behaviorally female, even though they have only one “sex” chromosome
Intelligence of Turner syndrome
Normal intelligence
Stature of Turner syndrome
Short stature
Describe gonads in Turner syndrome
Ovarian dysgenesis (“streak ovaries”) and infertility in most
- Premature ovarian degeneration accounts for infertility
- Most will not undergo puberty without hormone replacement
Describe abnormalities of Turner syndrome
Fetal and congenital edema, cystic hygroma (a fluid-filled sac, usually over the neck), cardiac anomalies, renal anomalies, pedal edema (puffy feet) in the newborn
Most Turner syndrome have genotype
45,X
Recurrence of Turner syndrome
Unlikely
Klinefelter syndrome genotype
47,XXY
Gender of Klinefelter
Occurs only in males
Phenotype of Klinefelter
Physically and behaviorally male
Describe abnormalities of Klinefelter
Small testes without sperm; gynecomastia (breast enlargement); poor pubertal development
without hormone replacement; tend to have relatively long limbs
Virility of Klinefelter
Almost all are sterile
Intellectual level of Klinefelter
earning disabilities,speech delays, and behavior disorders are common
However, Data from postnatal diagnoses are artificially biased toward abnormality
Recurrence risk of Klinefelter
Recurrence risk depends on the mother’s age at the time of the affected baby’s birth
Describe 47, XXX gender
Physically and behaviorally female
Appearance of 47, XXX
Normal appearance
Intelligence of 47, XXX
Often low-normal intelligence or mild M.R., but many are normal; speech delays, and/or behavior
difficulties common
However, Data from postnatal diagnoses are artificially biased toward abnormality
Empiric risk for trisomies is based on? Exceptions?
Empiric recurrence risk for trisomies (but not for XYY, Turner syndrome, or structural chromosomal anomalies) is based on the mother’s age at the time of the affected baby’s birth
Cri du Chat is known as? Example of?
del 5p (Cri du Chat syndrome) – example of a deletion syndrome in which the deletion may be visible microscopically or may be submicroscopic
Typical feature of del 5p?
Cat-like cry in infancy
Intelligence of del 5p?
Intellectual disabilites
Williams syndrome is an example of?
example of a microdeletion syndrome that is always submicroscopic
Describe the microdeletion in Williams syndrome. What does it include?
Microdeletion of chromosome 7q11.23, including the elastin gene
Describe the phenotype of Williams disease
Characteristic facial features
Heart defects common (certain types more common than others)
Hypercalcemia (abnormally high calcium in the serum)
Describe the behavior of Williams syndrome
Characteristic behavioral/neurodevelopmental phenotype
1. Mild-moderate intellectual disabilities (language ability much better than cognitive ability)
2. Distinctive friendly, loquacious personality
F. Recurrence is uncommon (<1%); rarely, the deletion
Describe the tone of Prader-Willi syndrome
Severe congenital hypotonia (born with very low muscle tone; “floppy”)
1. Causes early, severe feeding difficulties
Behavior of Prader-Willi
Typical behavioral phenotype
1. As the hypotonia improves, they develop hyperphagia (severe overeating) and obesity
Physical features of Prader-Willi
Mild, recognizable facial features
- Relatively small hands and feet
- Hypogenitalism (more recognizable in males)
- Short stature
- Cognitive impairment, usually mild intellectual disabilities
- Behavioral disorders
Describe the etiology of Prader-Willi
Cytogenetic or molecular abnormality at 15q11-q13 with abnormal DNA methylation analysis
a) Deletion involving the paternally-inherited 15q
b) Maternal uniparental disomy (i.e., both #15’s were inherited from the mother and none from the father)
Describe recurrence of Prader-Willi
Rare
Higher risk if imprinting control element is at fault
Lesser risk if chromsomal translocation has occured
Minimal risk if from a deletion or uniparental disomy
Tone of Angelman syndrome
Jerky, “puppet-like” gait; poor balance
Physical characteristics of Angelman
Microcephaly
Seizures
Intellectual level of Angelman
Severe intellectual diabilities
Behavior of Angelman?
Appear unusually happy
Etiology of Angelman
Cytogenetic or molecular abnormality at 15q11-q13 with abnormal DNA methylation study
a) Deletion involving the maternally-inherited 15q
b) Paternal uniparental disomy for #15 (5%) (i.e., both #15s were inherited from the father and
none from the mother)
Angelman mutation?
7% or so have mutation in UBE3A gene
Recurrence risk of Angelman
Depends on mechanism
DiGeorge/Velocardiofacial syndrome is known also as?
22q11.2 deletion syndrome
Characteristics of DiGeorge
Markedly variable physical features, but some common patterns
- Cleft palate
- Heart anomalies common, especially defects of conotruncal development of isolated conotruncal cardiac anomalies
- Often have characteristic facial features; a variety of other anomalies
- Immune deficiencies
- Hypocalcemia (abnormally low serum calcium); due to hypoparathyroidism (poor function of the parathyroid gland, which regulates calcium level)
Intelligence of DiGeorge
Learning disabilities or mild or moderate intellectual disabilities common, but many have normal
intelligence
Recurrence risk of DiGeorge
Recurrence risk depends on whether the deletion was inherited or occurred de novo in the patient
Need to test parents even if normal (7% have deletion)
