Chromosomal Defects Flashcards by Katalina Yandell

What do ~20% of infant deaths in US results from?

Birth defects

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When is the maternal serum screen (MSS) done?

15-20 wks gestation

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What three malformations does MSS look for?

Trisomy 21
Trisomy 18
Neural tube defects

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What levels of AFP, uE2 and hCG show in Trisomy 21?

AFP - low
uE2 - low
hCG - high

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What levels of AFP, uE2 and hCG show in Trisomy 18?

Low in all

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What levels of AFP, uE2 and hCG show in Neural Tube Defects?

AFP - high
uE2 - normal
hCG - normal

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Define anomaly.

A structural defect of any type

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Define malformation.

Intrinsic; genetic

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Define deformation.

Extrinsic; mechanical

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Define disruption.

Extrinsic; teratogen exposure

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Define syndrome.

Multiple anomalies that occur independently, but are cause by a single defect

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Define sequence.

When a structural or mechanical factor leads to multiple secondary effects

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What are some general characteristics of multifactorial disorders?

Disorders that tend to run in families
No single gene or chromosomal abnormality is responsible
Usually a combination of genetics & environmental factors required for phenotypic expression
Do not follow Mendelian patterns of inheritance

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What are some general characteristics of whole chromosome disorders?

Usually incompatible with life
Rarely reproduce
Most directly linked to maternal age
May occur in autosomes or sex chromosomes
Detectable via karyotype analysis

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What are some examples of Multifactorial disorders?

Coronary artery disease
IDDM
Hypertension
Some forms of cancer
Some developemental defects including:
Congenital heart defects
Spina bifida
Anencephaly
Cleft palate

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What is XXX?

A common abnormal karyotype also known as super female.

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What is XO?

Turner syndrome

The only recognized monosomy

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What is XXY?

Klinefelter syndrome

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What is XYY?

A common abnormal karyotype also known as super male.

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What are some symptoms of Klinfelter Syndrome?

47, XXY
1st recognized sex chromosome abnormality
Tall
Low IQ
Infertile
Hypogonadism
Gynecomastia

What are some symptoms of Turner Syndrome, the only true monosomy?

45, XO
Short
Infertile
Normal IQ
Webbed neck
Broad chest/wide set nipples
25% mosaics

What is fragile X syndrome?

An X-linked disorder that about 1/1500 males get

What is fragile X syndrome characterized by?

Mild connective tissue dysplasia
Macro-orchidism
Dental crowding

What is fragile X syndrome caused by?

By GCC repeats in 5’ UTR of FMR1 gene

What are the normal, submutation and Fragile X values for the GCC repeats?

Normal = 29 repeats Submutation = 29-230 repeats Fragile X = >230

What gene is silenced in fragile X syndrome and how?

FMR1 silenced via methylation

What is trisomy 21, 18 and 13?

``` 21 = Down syndrome 18 = Edward syndrome 13 = Patau syndrome ```

What are the clinical features of trisomy 21?

``` Mental retardation Epicanthic folds Hypotonia Simian creases Short stature Furrowed tongue Heart defects Predisposed for leukemia Brush field spots on iris Gap b/w 1st and 2nd toes Neurofibrillary tangles Duodenal obstruction ```

What is the incidence of trisomy 18?

1:8000

What are the clinical features of trisomy 18?

``` Mental retardation Rocker-bottom feet Malformed ears Hypoplastic nails Rarely survive past infancy ```

What is the incidence of trisomy 13?

1:25000

What are the clinical features of trisomy 13?

Lethal by 6 mo Severe CNS malformations Often cleft lip/cleft palate 70% have holoprosencephaly

What are the features of Cri du chat syndrome?

``` 5p deletion Microcephaly Micrognathia Hypertelorism Malformed ears Severe retardation ```

What are Robertsonian Translocations?

Translocations between 2 acrocentric chromosomes

What translocation is associated with a familial form of Down Syndrome?

14q;21q

What are teratogens?

Drugs, chemicals & infectious agents that may adversely affect fetal development

What are important factors that affect the outcome of teratogen exposure?

Time of exposure Dosage Fetal/Maternal genotype

What are some examples of drugs/chemicals that act as teratogens?

Thalidomide Retinoic acid (Accutane) Alcohol Hydantoin (Dilatin)

What do ACE inhibitors do as teratogens and at what point do they cause these problems in pregnancy?

kidney defects; in the 2nd and 3rd trimester

How bad are antineoplastic agents as teratogens?

Severe

What type of effects does mercury have as a teratogen?

Neurotoxin with cerebral-palsy like syndrome

What is an example of a lack of a morphogen?

Folate which is critical for neural tube development

What does a maternal deficiency in Vitamin A (Retinoid Acid) lead to?

Small eyes (microphthalmia) Cleft palate/lip Cardiovascular & urogenital anomalies Malformed limbs

What are the clinical features of Fetal Alcohol Syndrome?

``` Major cause of mental retardation Skeletal defects Growth retardation Heart Defects Smooth philtrum 1 in 6 have cleft palate ```

What are the clinical features of Fetal Hydantoin Syndrome?

Craniofacial anomalies Growth retardation Mental retardation Limb defects

What is the degree of severity linked to in fetal hydantoin syndrome?

Low activity form of epoxide hydrolase in mother

What are the teratogenic infections?

``` TORCH Toxoplasmosis Other: HIV, Syphilis, VZV Rubella CMV HSV ```

What symptoms may come from maternal diabetes mellitus?

Cardiovascular defects | CNS defects

What symptoms may come from maternal phenylketonuria?

Microcephaly Congenital heart defects Retardation