Genetics, Metabolic Flashcards
Trisomy 18 Cardiac Defect
VSD
Trisomy 18 Features
Edward Syndrome: Rocker bottom feet, overlapping fingers, VSD
Trisomy 13 Features
Patau Syndrome: Midline Defects: clefts, postaxial polydactyly, holoprosencephaly, clenched hands
Single Nails, think
Apert Syndrome
Achondroplasia features
short stature, rhizomelic shortening
trident hands
macrocephaly
Achrondraplasia inheritance
AD, FGFR3
increased with older paternal age
Algaille Cardiac features
Pulmonary Stenosis or TOF
Algaille Inheritance
chromosome 20 deletion, JAG1 gene
BOR syndrome stands for
brachia-oto-renal syndrome
BOR syndrome features
brachial clefts/fistulas
preauricular pits
hearing loss
renal dysplasia
Prader Willi Features
hypotonia at birth
small hands and feets, with obesity
small testes
Complications of Achrondroplasia
serous OM
motor delays
spinal stenosis
cord compression
Infantile Spasms associated with what syndrome
Tuberous Sclerosis
Wrinkled Palms and soles, think
EDS
Treacher Collins Syndrome Features
micrognathia (madnibular and maxillary hypoplasia)
ear malformations
Fragile X Syndrome
most common inherited ID syndrome
things are large: long face, large ears, large hands and feet, macroorchidism after puberty
Myotonic Dystrophy Genetics
AD
CTG repeat
anticipation, more severe when passed from mother
Myotonic Dystrophy Features
progressive weakness and wasting; facial and jaw muscles
shake your hand, but can’t let go
Cornelia De Lange Syndrome, Features
syndactyly of toes
microcephaly, IUGR,
long eyelashes & hirsutism
Tuberous Sclerosis Genetics
AD
TSC1 or 2
Tuberous Sclerosis Skin Findings
Ash leaf spots: hypopigmented macules
Shagreen Patches: oval shaped nevoid plaque on trunk or lower back
Tuberous Sclerosis other features
cortical tubers
renal angiomyolipomas or renal cysts
PCKD
rhabdomyomas
Wardenburg Syndrome
albinism, white forelock, graying
cleft lip/palate
cochlear deafness
NF 1 Features
cafe au lait, freckling, neurofibromas
optic gliomas, Lisch nodules
sphenoid dysplasia
NF 2 Features
bilateral vestibular schwannomas/acoustic neuromas
lens abnormalities
Proteus Syndrome
macrodactylyl
soft tissue hypertrophy
hemihpyertrophy
accelerated growth
Cleidocranial dysostosis
brachycephaly, frontal bossing
wormian bones (abnormal intrasutural bones)
supranumeray teeth
GI diseases associated with down syndrome
hirschsprung and duodenal atresia
OI & Blue Sclera
Type I and Type 3 (but lighten)
OI & Type 4
white sclera
milder
tibial bowing
OI Type 2
most severe, death in the newborn period due to respiratory insufficiency
WAGR is absence of which genes
WT1 (Wilms)
PAX6
multilocular cystic mass in nuchal region
think cystic hygroma
Crowe Sign
freckles in axilla, NF
Sturge Weber Syndrome Features
Port-Wine Stain in V1 distribution
glaucoma
leptomeningeal angiomatosis –> seizures
Ghent Criteria for Marfans
ectopic lens
aortic dilation or dissection
family history
Brushfield Spots
normal or associated with trisomy 21
ring appearance or “speckled irises”
lower eyelid absents, think
Treacher Collins
NF Type 1 CNS findings
focal areas of T2 weighted intensity
Stickler Syndrome
Pierre Robin Sequence
Difference Between Marfans and Homocystinuria
Learning Difficulities
omphalocele associated with what trisomy
13
Propionic Acidemia - what it is
defieicny of propionyl-CoA carboxylase which oxidizes VoMIT (valine, methionine, isoleucine, threonine)
- gets get sick and vomit (ketoacidosis w or w/o hyperammonmina)
Propionic Acidemia Complictions
malnutrition, FTT, recurrent infections, cardiomyopathy, pancreatitis
MPS - Type 1
Hurler Syndrome, AR
coarsened facial features + corneal clouding
macrocephaly, deafness
atlantoaxial sublaxation
MPS - Type 2
Hunter Syndrome, X-linked
No corneal clouding
Type 1 Glycogen Storage Disease
von Gierke Disease
deficit of glucose-6-phosphatase
doll like faces with fat cheeks
Type 2 Glycogen Storage Disease
Pompe Disease, however lysosomal storage disease
deficiency of lysosomal acid alpha1-4-glucosidase
infantile, juvenile and adult forms
Type 5 Glycogen Storage Disease
McArdle Disease
deficiency of muscle phospharylase
rhabdo after exercise, often 20s-30s
deficit of glucose-6-phosphatase
T1 GSD/von Gierke Disease
deficiency of lysosomal acid alpha1-4-glucosidase
Pompe Disease/GSD T2
Infantile Pompe Disease
cardiomegaly, hypotonia and death before 1 year
HCM
deficiency of muscle phospharylase
McArdle Disease, GSD T5
Most common lysosomal storage disease?
Gaucher Syndrome
Types of Gaucher Disease
Type 1 - most common, Ashkenzai Jews (no CNS)
Type 2 - Acute Neuronopathy (CNS)
Type 3 - Subacute neuronopathy (CNS)
deficiency of lysosomal glucocerebrosidase
Gaucher Disease
Type 1 Gaucher Disease Presentation
splenomegaly, abdominal protruberance –> thrombocytopenia
Growing pains
Galactokinase Deficiency presentations
cataracts (nothing else!)
Triad of carboxylase deficiency (biotinidase or holocarboxylase sythentase deficiency)
encephalopathy
alopecia
skin rash
Niemann-Pick Disease Deficiency of
A, B - spingomyelinase (lysosomal storage)
C - buildup of GM2 gangliosidosis / cholesterol accumulation (not lysosomal storage!)
Niemann Pick C Clinical Presentation
3-5 years with poot school performance and impaired motor skills (ataxia)
supranuclear vertical-gaze palsy/dolls eye reflex preserved
C’s; cholesterol, childhood alzheimers (dementia), Can’t C Up and Down (vertical gaze palsy)
PKU - Genetics
AR
phenylalanine cannot be converted to tyrosine
PKU - Symptoms/Presentation
intellectual disabsility
vomitting in childhood
mousy or wolflike odor
fair haired, fair skinned
Maternal PKU
presents similar to FAS
3 Branched Chain Amino Acids
Valine, leucine, isoleucine
odor of mousy/wolf-like
PKU
odor of sweaty feet
Isovaleric Acidemia
Leesch-Nyhan Syndrome
X-linked HGPRT deficiency
FTT, self-mutilation
MCAD symptoms
first 2 years of life: fasting induced lethargy and hypoglycemia, arrythmias
evlevated C6 and C8 esters
VCLAD Deficiency
infancy: arrhythamis, CM, death
C14-18 esters
LCHAD Deficiency
cholestatlic liver disease
retinopathy with hypopigementation
Galactosemia at risk for what infection
E coli sepsis
Galactosemia is a deficiency of
GALT, galactose can’t be metabolized
Galactoasemia presentation
first few days of life with jaundice, HSM, vomiting, seizures
Cataracts, vitreous hemorrhage
Kearns-Sayre and Chronic Progressive External Ophthalmoplegia (CPEO) Syndrome
ptosis
ophthalmoplegia
ragged-red fiber myopathy
Fabry Disease
Febrile episodes, foam cells Angiokeratomas, alpha galactosidase Burning pain in hands and feet Renal Failure YX, male, X-linked CV disease
Tay Sachs Genetics
AR, mutation in HEXA gene
distruption of enzyme B-hexoasminadase A
build up of GM2 gandlioside
Tay Sachs Infantile Form presentation
first few months of life
enhanced startle reflex
cherry-red spot
progressive loss of motor skills
Sanfilippo Syndrome
MPS Type 3
severe CNS involvement
sweet urine smell
MSUD
MSUP genetics
defect in deoxycarboxylation of ketoacids
HAGMA and increased BCAA
MSUD presentation
early in infancy, quickly declines with death in 2-4 weeks
sweet smell
Homocystinuria characteristics
marfinoid habitus
downwards lens dislocation
increased risk of thromboembolism
Homocytinuria treatment
pydrixodine
Urea cycle disorders present with
elevated ammonia, low BUN, respiratory alkalosis
Glutaric Acidemia Type I
subdural hematomas and retinal hemorraghes (looks like child abuse)
Communicating Hydrocephalus common in
Hunter Syndrome
Finding of L-isoalloleucine
MSUD
Tyrosinemia
accumulation of succinylacetone
Rickets, RTA
Renal and Liver Failure without hypoglycemia
OTS (ornithine transcarbamylase def) versus CPS (carbamoyl phosphate synthetase 1)
Orotic acid HIGH in OTC
low in CPS
Hunter Syndrome complication later in life
cardiac
ADHD with hyperpigmentation, think
adrenaleukodystrophy (very long chain fatty acid)
Glycogen Storage Disease Mnemonic
Villanous President Called and Molested Here 1 Von Gierke 2 Pompe 3 Cori 4 Andersone 5 McArdle 6 Hers
