FMS Week 2 Flashcards
signs and symptoms of cystic fibrosis
neonatal: bowel blockage (meconium ileus), abdominal calcifications
Infancy: failure to thrive, chronic diarrhea, pneumonia.
childhood: nasal polyposis, intussusception
adulthood: nasal polyposis, bronchiectasis, delayed puberty, male reproductive issues (azoospermia)
characteristics of trisomy 18
low frontal hairline, narrowed eyelids, blunt nasal tip with small nostrils, small chin, “fawn” ears, high nasal bridge
life expectancy of trisomy 13
10% beyond a few months
what is germline mosaicism?
when a parent contains either multiple distinct cell lines or a de novo mutation arises in reproductive cells, resulting in inheritance from otherwise non genotypic parents
cosanguinity
more commonly in pedigrees involving recessive diseases, the amount of shared DNA due to relation
Lesch-Nyhan disease
x-linked recessive, cannot reclaim purines, defect in HGPRT, neurologic disfunction and self mutilation, clinical suspicion and elevated uric acid, treated with low purine diet, allopurinol, and other symptomal medications
Phenylketonuria
Autosomal recessive, loss of phenylalanine hydroxylase (PAH) activity. Accumulation of PHE because it cannot be converted to tyrosine
signs/symptoms of turner syndrome
increased nuchal fold, congenital heart defects, lack of puberty, edema in hands/feet, scoliosis/kyphosis, streak ovaries
Ideal testing for 22q11 deletions
probably FGH, FISH is also useful in the “nested region”
characteristics of trisomy 13
holoprosencephaly, atypical median cleft lip, microphthalmia, closed hand, polydactyly, cryptorchidism, congenital heart disease, cystic kidneys
Hereditary fructose intolerance
autosomal recessive, cannot metabolize fructose to glucose (inactive fructoaldolase (aldolase B)), vomiting and hypoglycemia, hepatomegaly and renal disfunction, clinical suspicion, restrict fructose consumption
origin of williams syndrome
varying 7q11 deletions
Wolf-Hirschorn syndrome
pre/postnatal growth deficiency, broad nasal root (greek warrior helmet), developmental delays, seizures, hypotonia
Describe genetics of cystic fibrosis
mutations in CFTR, a chloride channel gene. Autosomal recessive, most common in caucasians
Lipid disorder and characteristic
Medium acyl-CoA dehydrogenase (MCAD): Diagnostic intermediates on urine organic acid quantitation
original names of 22q11 deletion syndrome
digeorge or velocardiofacial
best testing for Williams syndrome
CGH
what are the issues with CGH
deviation has to be compared to that of normal CNVs, cannot detect balanced translocations
FBN1 gene
fibrillin protein, associated with Marfan syndrome
increased nuchal fold, congenital heart defects, lack of puberty, edema in hands/feet, streak ovaries
turner syndrome
banding patterns
the “address” of genetic locations on a chromosome determined by varying stains, each band can contain many genes
Treatment of Turner syndrome
cardiology/renal consultation, audiology evaluation, genetic counseling, support group referral, regular monitoring, supraphysiological growth hormone doses, high estrogen/steroid doses
Purine/Pyrimidine disorder and characteristic
Lesch-Nyhan syndrome: hyperuricemia
SRY gene
deletion on Y chromosome leads to XY female syndrome
what is dysmorphology?
the study of birth defects
urea cycle defect and characteristic
Ornithine transcarbamylase: elevation of ammonia and diagnostic amino acid
LCR
low-copy repeats, repetitive segments with 95% sequence identity, mismatch during crossing over leads to deletions
translocation down syndrome
3rd copy of 21 on p arm of 14 or 22.
t(14;21)
hunter syndrome
Iduronidase-2 sulfatase defect, x linked recessive, accumulation of mucopolysaccharides (dermatan and heparin), diagnosed by enzyme assay, treated with enzyme replacement
carbohydrate disorder and characteristic
hereditary fructose intolerance: clinical suspicion
Ideal testing for turner syndrome
definitely karyotype, FISH recommended due to gonadoblastoma risks of Y chromosome material
describe genetics of phenylketonuria
autosomal recessive, Variable prevalence among global populations, variable expression
Describe achondroplasia?
FGFR3 gene, autosomal dominant, short-limbed dwarfism, obstructive apnea and some developmental motor delays, complete penetrance
WAGR syndrome
deletion at 11p13, WT1 gene, genital anomalies, retardation of growth and development, aniridia
origin of 22q11 deletion syndrome
90% de novo, autosomal dominant in appearance
what is mendelian inheritance?
single gene inheritance, pedigree analysis, autosomal or sex-linked, dominant or recessive
karyotype of turner syndrome
absence of all or part of X chromosome, 50% 45,X. 25% mosaic (can include Y), various deletions etc.
characteristics of Williams syndrome
aortic stenosis, depressed nasal bridge, epicanthal folding, eye puffiness, blue eyes, wide mouth, delayed development, cocktail personality, hypercalcemia
describe the penetrance of autosomal recessive traits
complete penetrance, no alternative copy
5p- syndrome
“cri du chat”, hypotonia/laryngeal abnormality, growth restriction, microcephaly, round face/spaced eyes, single palmar creases, moderate/severe intellectual disability
Vitamin disorder and characteristic
Biotinidase: clinical suspicion and relevant lab studies
what is the life expectancy of trisomy 21
55-60 years
characteristics of 22q11 deletion syndrome
congenital heart disease, palatal abnormalities, velopharyngeal incompetence, characteristic facial features, learning difficulties, immune deficiency, hypocalcemia, hearing loss
biotinidase disorder
cannot reclaim/recycle biotin, an important vitamin in carboxylation reactions, symptoms include alopecia, dermatitis, deafness, seizures, and neurologic deterioration starting about 4 to 6 months of age, diagnosis by enzyme assay, treated with biotin supplementation
BMPR1A gene syndromes
juvenile polyposis syndrome (JPS), polyps in the GI tract, juvenile refers to type of polyp, bleeding and anemia, mostly benign, increased risk of GI cancers
Methylmalonic Aciduria
autosomal recessive, acidosis in first week of life potentially coma, lack of methylmalonyl-CoA mutase, cannot convert methylmalony.-CoA into succinyl-CoA in Krebs cycle (catabolism of amino acids, cholesterol, fatty acids), methylmalonic acid is elevated, treated by low dietary protein and B 12 supplements
Ornithine transcarbamylase deficiency
X linked recessive, severe neurologic damage, low citrulline levels, build up of ammonia, treated by low protein diet and ammonia scavenger medications
FGFR3 gene
negative regulator of bone growth, associated with achondroplasia
recurrence risk of trisomies
1% (unless robertsonian translocation)
juvenile polyposis syndrome
BMPR1A gene syndrome
Describe Marfan syndrome?
FBN1 gene, effects fibrillin protein, dilated aortic root, ectopia lentis, dural ectasia, Autosomal dominant, 100% penetrance
Amino acid disorder and characteristic
phenyketonuria: elevation of diagnostic amino acids on amino acid quantitation
Achondroplasia inheritance
80% de novo, autosomal dominant, most are hemizygotes
MCAD
medium chain acyl-CoA dehydrogenase deficiency, lethargy and vomiting following fasting, hypoglycemia, hepatomegaly, elevated fatty acid intermediates, treated by avoiding fasting and rapid treatment of hypoglycemia
what is the leading genetic cause of intellectual disability
aneuploidy
Describe the inheretence of neurofibromatosis?
NF1 gene, Autosomal dominant, 100% penetrance, variable expressivity, 1/2 of all cases de novo
life expectancy of trisomy 18
10% beyond a few months
Lysomal storage disorder and characteristic
Hunter syndrome: clinical and radiologic signs/symptoms
organic acid disorder and characteristic
methylmalonic aciduria: elevation of diagnostic acid in urine
what are the issues with mendelian inheritance?
doesn’t account for de novo mutations or germline inheritance
Describe genetics of sickle cell disease
point mutation producing HbS gene. autosomal recessive. heterozygotes have 40% HbS, homozygotes 100%
