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79 Cards in this Set
- Front
- Back
most structural birth defects are determined during:
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weeks 3-8
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malformation =
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inborn/congenital error of morphogenesis
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best examples of malformations:
(3) |
1. cleft lip/palate
2. neural tube defects 3, polydactyly |
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70% of NTD's can be prevented with:
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folic acid throughout child-bearing years
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deformations are the result of:
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mechanical forces
e.g. club foot, bowed legs |
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deformation is most common in the:
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third trimester
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disruption =
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extrinsic breakdown of, or an interference with, an **originally nl** developmental process
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best example of disruption =
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amniotic bands
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dysplasia =
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**an abnl organization of cells** into tissues and its morphologic results
- m.c.ly skeletal dysplasias, ectodernal dyslpasias |
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skeletal dysplasias often have associated:
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malformations,
deformations |
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tissues derived from ectoderm:
(5) |
1. skin
2. hair 3. teeth 4. nails 5. hearing |
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malformation ~~
deformation ~~ disruption ~~ dysplasia ~~ |
congenital;
mechanical forces; interference of nl development abnl tissue |
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examples of minor anomalies:
(7) |
1. head shape
2. ear size/morphology 3. eyes (spacing, telecanthus) 4. hair patterning (widow's peak, low posterior hairline, cowlik/frontal upsweep) 5. palmar creases 6. finger/palm dermal ridge patterns 7. ridges on finger pads |
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many syndromes are recognized by:
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their constellation of minor anomalies
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some minor anomalies run in families in AD fashion;
but the presence of 3 or more suggests: |
an underlying, more widespread defect in morphogenesis
(e.g,. a syndrome of chromosomal or single gene cause) |
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telecanthus =
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loss of M white sclera
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features of Waardenburg type 1:
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1. telecanthus
2. white forelock |
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posterior pits on the back of the ear suggest:
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fetal overgrowth
(big babies, twins) |
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difference between sequence and syndrome:
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sequence = SINGLE, PRIMARY defect with secondary or tertiary anomalies
i.e. cascade of problems derived from a single known cause syndrome = MULTIPLE primary anomalies running together - more than one tissue, organ system, developmental field, or region of the body is dysmorphic, dysplastic, dysfunctional, or dystrophic |
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example of a sequence:
(3) |
1. NTD
2. hydrocephalus 3. talipes (club foot) |
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3 causes of syndromic malformations:
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1. chromosomal abnormalities (genomic mutations)
2. single gene mutations (Mendelian disorders) 3. teratogens |
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classic FAS facies =
(2) |
1. small eyes
2. smooth philtrum |
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the “classic FAS face” only occurs with an exposure during:
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early gastrulation,
~ day 17 in humans Exposures at other times clearly affect the development of the CNS and other organ systems, but do not cause the FAS facies - looking for FAS by looking for facies will miss the point |
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Fetal Alcohol Spectrum Disorders (FASD) include:
(3) |
1. FAS
2. ARND (alcohol-related neurodevelopmental disorders) 3. ARBD (alcohol-related birth defects) |
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other systems affected by FAS:
(4) |
1. CV CNS: structural and functional
2. Poor linear growth, wt gain 3. Kidney 4. many others |
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"nonsyndromic" malformations =
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isolated malformations
i.e. only ONE primary malformation - all others are coincidental |
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best examples of nonsyndromic malformations:
(4) |
1. ID
2. autism 3. HTN 4. Alz |
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"multifactorial" ~~
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genetic predisposition interacts with environment to move a person past the threshold and into "affected" state
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“Complex” =
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combination of both single gene and multifactorial causation
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Intellectual disability ~~ not only to low IQ but also to:
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dec. in adaptive skills
- daily living, communication, social |
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most causes of ID are:
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unknown
- after that, chromosomal |
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any child with ID without a clear-cut diagnosis should have:
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chromosome analysis and/or chromosome microarray
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main difference b/w karyotype and microarray:
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microarray looks much closer, can pick out much smaller deletions or duplications
(gain or loss) |
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neuroimaging for FX syndrome:
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MRI
- avoid CT if possible |
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features of Williams syndrome:
(8) |
1. very friendly
2. great musical ability 3. delayed milestones 4. mild ID 5. hypercalcemia 6. heart issues 7. puffiness around eyes 8. big lips |
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2 genes associated with deletion of 7q11.23 in Williams syndrome:
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1. ELN (elastin)
2. LIM-kinase 1 |
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most cases of Williams syndrome are:
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de novo deletions
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testing for Williams in other family members:
(2) |
1. offer chrome. testing with FISH to parents
2. if nl, low recurrence risk; other family members not at risk |
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cleft L/P is most commonly:
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non-syndromic (~70%)
- vs. syndromic |
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features of non-syndromic cleft L/P, wrt pt:
(3) |
pt has
1. no other anomalies 2. no recognized maternal/environmental exposures 3. multifactorial inheritance |
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teratogens that may contribute to cleft LP:
(4) |
1. Alcohol
2. Tobacco 3. Antiepileptic drugs (dilantin, valproic acid) 4. Thalidomide |
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recurrence risk for cleft LP increases with:
(4) |
1. severity of trait
2. number of affected relatives 3. male fetus 4. how closely related the baby is to family member with cleft LP |
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examples of cleft LP of syndromic origin:
(5) |
1. trisomy 13
2. 4p minus syndrome (Wolf-Hirschhorn) 3. 22q deletion syndrome 4. Van der Woude syndrome 5. Native American myopathy |
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2 features of trisomy 13:
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1, microcephaly
2. polydactyly |
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trisomy 13 is severe;
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majority die during the first year
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22q deletion syndrome ~~
(3) |
1. split uvula (mild cleft)
2. hypocalcemia 3. learning disabilities/psychiatric disorders |
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features of Van der Woude Syndrome:
(4) |
1. AD - that's why you want to test the parents
2. recurrence risk at 50% 3. single gene mutation in IRF6 gene on 1q 4. subtle - lip pits in parents suggest VdW |
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4 features of NA myopathy:
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1. mut. in STACC3 gene
2. AR 3. club feet, other contractures 4. risk of malignant hyperthermia under gen. anesthesia - and often NEED surgery too |
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m.c. cause of Robin sequence =
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Stickler syndrome
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features of Stickler syndrome:
(3) |
1. vision problems
2. hearing problems 3. early arthritis |
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cleft can also be caused by:
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amniotic bands
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inheritance of Marfan syndrome:
(2) |
1. AD
2. 25% de novo mut's |
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incidence of Marfan =
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1 / 10,000
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features of Marfan:
(8) |
1. aortic root dilation/dissection
2. MVP 3. myopia, early-onset cataracts tall stature with long, thin arms and legs, nl trunk 4. arachnodacytly (long, thin, “spider-like” digits) 5. scoliosis 6. pectus excavatum or carinatum (hollow or pigeon chest) 7. pes planus (flat feet) 8. typical facies |
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mut's of Marfan:
(3) |
1. allelic heterogeneity
2. various mutations within the FBN1 gene on chromosome 15q21 3. various mut's protein fibrillin |
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dx of Marfan based on:
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phenotype
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management of Marfan:
(5) |
1. Cardiac features are life threatening - req. life-long follow-up.
2. B-blockers 3. annual ophthalmologic exams 4. no contact sports or strenuous activity 5. if preg, need to be careful about aortic dissection/rupture |
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Leigh syndrome =
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progressive neurologic disease with motor and intellectual disability
due to mitochondrial |
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features of Leigh:
(10) |
1. onset typically b/w 3-12 months, s/ts after viral illness
2. ~~ periods of deterioration followed by “plateaus” with stabilization of symptoms 3. poor suck 4. vomiting/irritability/failure to thrive, loss of head control, and loss of motor skills 5. sez's 6. hypotonia/muscle weakness/ataxia 7. eye problems 8. LA is often present during periods of deterioration 9. hypertintense lesions in the BS or BG on T2-weighted MRI 10. cardiac, hepatic or renal features. ~50% of individuals die by 3 years secondary to respiratory or cardiac failure |
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incidence of Leigh =
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1 / 40,000 (all causes)
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inheritance of Leigh:
(3) |
1. locus heterogeneity
2. Mendelian (AD, X-linked) 3. or mitochondrial |
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NARP =
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Neurogenic muscle weakness, Ataxia, and Retinitis Pigmentosa
- retinitis starts as salt and pepper retinopathy |
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features of NARP:
(5) |
1. childhood or YA onset
2. learning disabilities and developmental delays in child NARP 3. adult NARP ~ decline in ID 4. muscle weakness, ataxia, retinitis pigmentosum 5. mitochondrial inheritance |
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relationship of MT-ATP6 gene to NARP and Leigh:
(3) |
1. mutant loads <60% are either asymp or have mild symptoms
2. ~70-90% have NARP 3. >90% have Leigh syndrome |
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NF1 is dx'd on clinical symps - at least 2 of the following:
(6) |
1. 6 or more café au lait spots
2. 2 or more neurofibromas of any type or 1 plexiform neurofibroma 3. axillary or groin “freckling” 4. an optic glioma 5. 2 or more Lisch nodules (benign, raised iris hamartomas seen by slit lamp exam) 6. a 1st-degree relative with NF1 |
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CLS =
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cafe-au-lait spots
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features of NF1:
(6) |
1. progresses with age
(starts as CLS; Lisch nodules and cutaneous fibromas develop late childhood to adulthood) 2. some features are age-dependent 3. increased risk for learning problems (40-60%) 4. sez's 5. HTN (due to renal artery stenosis or rarely, pheo) 6. ~ malignant neoplasms |
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incidence of NF1 =
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1 / 3000
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inheritance of NF1:
(3) |
1. AD
2. nearly complete penetrance, variable expression 3. 50% are de novo mut's |
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mut. of NF1:
(3) |
1. NF1 gene,
2. chromosome 17q 3. prot. is neurofibromin |
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gene testing for NF1:
(2) |
1. protein truncation testing,
sequencing, FISH, Southern blotting => 95% of 2. gene sequencing alone detects up to 89% of gene mut's |
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management of NF1:
(6) |
1. complications increase with age
2. if severe intellectual disability present, it would be evident early 3. optic gliomas and progressive scoliosis in childhood 4. plexiform neurofibromas before adulthood. 5. surgical removal of neurofibromas generally not recommended unless compromising essential organ 6. first-degree relatives need examination |
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genetic tests, in order from most broad to more specific:
(6) |
1. karyotype
2. FISH / 3. microarray 4. Sanger sequencing (single base and small microdeletions) 5. PCR (NT level) 6. all the other PCR-based approaches |
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unique management of Turner =
(3) |
1. screen for celiac dz
2. HRT around puberty 3. if karyotype includes a Y chromosome cell line, increased risk for gonadoblastoma |
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for a condition with MULTIPLE possible mutations (like CF), you want to do:
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DNA sequencing
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Hungtington dz =
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progressive disorder of cognition, motor, and psychiatric disturbance
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features of Huntington:
(6) |
1. motor symptoms include gait disturbance, progressive chorea, dysarthria
2. global decline in cognitive abilities occurs in ALL 3. significant personality changes affect 72% (may include intermittent explosiveness, apathy, aggression, alcohol abuse, paranoia) 4. late stages: wt loss, total dependence, no speech, dysphagia 5. mean age of onset is 35-44 (10% have juvenile onset before age 21 with seizures and more rapid decline) 6. avg. age of death is 55 years (suicide an issue) |
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incidence of Huntington =
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3-7 / 100,000 of Western Europe descent
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genetics of Huntington:
(5) |
1. AD
2. CAG repeat within HD gene 3. above 60 repeats ~~ juvenile onset 4. repeat expansion tends to occur during paternal gametogenesis => juvenile Hunt. inherited almost exclusively from affected fathers 5. PCR |