Dysmorphology Flashcards
What is dysmorphology? Who primarily practices it?
Branch of clinical genetics specializing in birth defects, studies the etiology and pathogenesis of abnormal morphogenesis.
It is primarily practiced by clinical geneticists
What is the leading cause of pediatric morbidity and mortality?
Birth defects -> affects 3-4% of children
What are the four categories of congenital anomalies?
- Malformations
- Deformations
- Disruptions
- Dysplasias
What is a malformation and give an example?
Defect in the morphogenesis / development of an organ or structure, usually occurring before 10 weeks gestation (very early)
i.e. syndactylyl, neural tube defects (spina bifida), hypoplasia of an organ
What is a deformation and give an example?
Alteration in shape, position, or structure of a body part which was PREVIOUSLY NORMAL - caused via mechanical forces.
Example: clubfoot, craniofacial asymmetry
What is arthrogryposis and what causes it?
Congenital joint contractions, caused via oligohydramnios or other amniotic cavity compression.
What is a disruption and what causes it? Give an example.
Destruction of tissue that was previously normal, caused by factors extrinsic to developing structure.
For instance, amniotic bands (fibrous bands of amnion) can constrict the fingers and cause loss of finger growth. Can also result from vascular insufficiency, trauma, or teratogens.
What is a dysplasia and what is it a subcategory of?
Abnormal cellular organization within tissue (single tissue type) resulting in structural changes, i.e. achondroplasia, since cartilage was previously forming normally.
It is a subcategory of deformations.
What is a sequence? Give an example with spina bifida?
A pattern of multiple defects resulting from a single primary pathophys mechanism.
Club foot (talipes equinovarus) and hydrocephalus can result from a neural tube defect due to changes in innervation and CSF pressure
What is the Pierre Robin sequence?
Restriction of mandible growth before 9th week can cause glossoptosis (tongue lies more posteriorly than normal) and cleft palate as a result.
What is Potter sequence associated with?
Oligohydramnios
What is an association? Give an example
A non-random occurrence of several anomalies which is not well understood or identified.
Example: VACTERL association
3 or more of the following: vertebral anomalies, anal atresia, cardiac, tracho-esophageal, renal, limb
What is a major vs minor anomaly? What do you have to consider for minor?
Major - impairs normal body function, often requiring surgery - i.e. cleft palate or congenital heart defect
Minor - little or no surgical, medical, or cosmetic significance, but occur in <5% of population i.e. epicanthal folds.
For minor: consider also the race of the patient
Why are minor anomalies important?
They can serve as markers for malformation, and patterns of these minor anomalies can suggest a syndromic diagnosis
How common are minor anomalies?
15% of people have 1 minor, 1% have 3+, and having 3+ gives you a 20% chance of having an associated major anomaly.
What is a teratogen and when is it most destructive?
A drug, infection, or environmental agent that causes birth defects, most destructive during critical developmental periods
If exposed later, did thalidomide cause only lower limb or upper limb defects?
Only lower limb defects, since upper limb critical period is earlier
What makes a major birth defect cause easy or hard to identify?
Hard - 60%, affecting only one organ system
Easy - affect multiple organ systems or accompanied by minor anomalies which indicate a “syndrome”
What is a single gene syndrome? Give an example which results from defect of FGFR2 gene
Syndrome caused by a single gene defect.
Apert syndrome - craniosynostosis, underdeveloped midface, syndactylyl
What type of syndrome is DiGeorge?
Microdeletion / microduplication class -> it is a 22q11 microdeletion syndrome.
What type of disorders cause club foot and how common is this?
Polygenic / multifactorial, hard to identify the inheritance. This makes up about 50% of syndromes
What are the features of fetal alcohol syndrome?
Growth restriction, microcephaly, cognitive impairment, characteristic facial features
What does congenital rubella syndrome cause?
Micrcephaly, petechiae, heart disease, glaucoma, cataracts, small eyes
What are the characteristics of holoprosencephaly?
Failure of forebrain to completely separate into two hemispheres, leads to clefting, hypotelorism (narrow-set eye distance) / cyclopia, pituitary dysfunction and developmental delay
What is a single gene causes of holoprosencephaly?
Loss of Sonic Hedgehog. Autosomal dominant, leads to variable phenotype within the family, some of which only have a single incisor as the minor anomaly.
What is a chromosome abnormality causing holoprosencephaly?
Trisomy 13
What factor in pregnancy can lead to holoproencephaly?
Maternal diabetes
What is the general idea of a genetic evaluation? What’s in it?
Get a complex genetic background and family history including 3 generations, maternal conditions and prenatal exposures, as well as postnatal history + physical exam in order to order the best genetic tests to determine what the genetic syndrome is rather than widely scanning
What are some of the challenges in making a diagnosis even if your analysis is good?
Features tend to change overtime, and some may not have emerged yet in your syndrome. Some conditions are rare or not well described, and have variable expressivity.
What do you want to do with a diagnosis once you have it?
- Appropriate management and surveillance
- Accurate prognostication and understanding of prognosis
- Accurately assessing recurrence risk for parents.
