Genetics.txt

VACTERL

Mode of inheritance of Huntington's disease

Mode of inheritance of Adult Polycystic Kidney Disease

Mode of inheritance of Neurofibromatosis NF

Mode of inheritance of Vestibular schwannoma NF2

Mode of inheritance of Protein C deficiency

Mode of inheritance of Myotonic dystrophy

Mode of inheritance of Familial retinoblastoma

Mode of inheritance of von Willebrand's disease

Mode of inheritance of Tuberous sclerosis

Mode of inheritance of Marfan syndrome

Mode of inheritance of Achondroplasia

Mode of inheritance of Hereditary spherocytosis

Mode of inheritance of Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease)

Mode of inheritance of Peutz-Jeghers syndrome

Mode of inheritance of PKU

Mode of inheritance of Sickle cell anemia

Mode of inheritance of Congenital adrenal hyperplasia

Mode of inheritance of Cystic fibrosis

Mode of inheritance of Gaucher's disease

Mode of inheritance of Tay-Sachs disease

Mode of inheritance of Galactosemia

Mode of inheritance of Wilson's disease

Mode of inheritance of Fanconi's anemia

Mode of inheritance of Duchenne muscular dystrophy

Mode of inheritance of Lesch-Nyhan syndrome

Mode of inheritance of Ornithine transcarbamoylase OTC deficiency

Mode of inheritance of Hemophilia A and B

Mode of inheritance of Fragile X syndrome

Mode of inheritance of Chronic granulomatous disease

Mode of inheritance of G6PD deficiency

Mode of inheritance of Color blindness

Mode of inheritance of Leber's hereditary optic neuropathy

Mode of inheritance of NARP

Mode of inheritance of MELAS

Mode of inheritance of MERRF

Mode of inheritance of Kearns-Sayre syndrome

15q 11-q13 father

15q 11-q13 mother

SGA, narrow nose, hypoplastic nasal alae
narrow bifrontal diameter
short sternum
congenital heart disease
overlapping fingers
rocker-bottom feet

postnatal growth retardation
scalp defects
cleft lip and palate
congenital heart disease
renal anomalies
omphalocele

no increased risk with maternal age
short stature
bicuspid aortic valve
coarctation of the aorta
lymphedema in infancy

many variants
no signs in prepubertal boys
postpubertal boys infertility, mild MR, gynecomastia, long limbs

long, tubular nose
cleft palate, bifid uvula
TOF, truncus, right/interrutped aortic arch, VSD, PDA
mild MR
absenct parathyroid, thymic hypoplasia
immunodeficiency, T-cell defects
neonatal hypocalcemia
psychiatric disease, including bipolar, schiziphrenia

microcephaly
cat cry in the newborn period
epicanthanl folds
cardiac defect
severe pychomotor retardation

short stature, periorbital fullness/puffy
neonatal hypercalcemia
stellate iris, antevered nares, thick lips, microdontia
supravalvular aortic stenosis, bicuspid aorta
pectus excavatum
nephrocacinosis
MR

brachycephaly, broad face
hearing loss
cardiac and renal abnormalities
MR, behavioral abnormalitis, self-destructive
sleep distrubances
decreased pain sensation

triangular face
anterior chamber anomalies
PPS, ASD, VSD
cholesatsis with intrahepatic duct deficiency
vertebral anomalies
mild MR
hypercholesterolemia, hypertriglyceridemia, abnormal LFTs

CHARGE

frontal bossing, megalencephaly
risk of foramen magnum stenosis
recurrent OM
conductive hearing loss
OSA
hydrocephalus
rhizomelia

4 types of OI and mode of inheritance

exophthalmos, macroglossia, hypoglycemia, macrosomia
hemihypertrophy, cardiomegaly, renal abnormalities
gonadoblastoma

short stature, triangular face
down-slanting palpebral fissures
hypertelorism
dental malocculusion
webbed neck, low posterior hair line
pulmonic stenosis
shield chest, wide spaced nipples
lymphedema
mild MR

microcephaly, long philtrum
hearing loss
synophrys, long, curly eyelashes
wide spaced teeth
limb abnormalities
cutis marmorata, hirsutism

postnatal growth retardation
microcephaly
beaked nose
cardiac abnormalities
broad thumbs with radial angulation, broad great toes
MR
increased risk of tumors, esp of head

large cutaneous hemangiomata
lymphangioma
asymmetric limb hypertrophy
macrodactyly
MR
Kasabach-Merritt syndrome

SGA lateral asymmetry and normal HC
cardiac defects
fifth-finger clinodactyly
cafe au lait spots
MR
risk of neoplasm

short stature
microcephaly, micrognathia
hypotelorism
ptosis, cataracts
VSD, ASD, coarc
micropenis
syndactyly of the second and third toes
MR, seizures, hypotonia
low cholesterol

Lisch nodules
optic glioma
hypertension, renal artery stenosis
cafe au lait spots, axillary freckling, plexiform neurofibromas
learning disabilitiss
increased risk of neoplams

achromatic retinal patches
cardiac rhabdomyoma
facial angiofibroma
ash leaf macules, shagreen patch, subcutaneous nodules
seizures, MR
intracranial calcifications

famililial cancer syndrome
4 types

hemangiomata ophthalmic branch trigeminal
MR
seizures

short stature, cutaneous telangiectasia
cerebellar ataxia
decreased or absent DTRs
thymic hypoplasia
hypersensitivity to ionizing radiation

urine smells of maple syrup
burned sugar
amino acid metabolism
onset first 5-14 days of life of lethargy, coma, developmental delay
measure plama leucine to diagnose
treatment is dietary restriction of leucine, isoleucine, and valine

urine smells of sweaty feet

cat urine

musty urine
deficiency of phenylalanine hydroxylase in the liver
severe MR if not treated
blond hair, blue eyes, eczema

urine smells of rancid butter, rotten cabbage

urine smells fishy

liver dysfunction with hyperbilirubinemia
hypoglycemia
coagulation problems
renal tubular dysfunction
cataracts
females infertile
increased association with e coli sepsis
positive reducing substances
elimination of dietary galactose is treament

marfanoid habitus
dislocated lense
MR
AV thrombosis

3 causes of hyperammonemia first 24 hours

Causes of hyperammonemia >24 hours

Causes of positive reducing substances

emesis, hypoglycemia, liver and kidney disease
symptoms arise after introduction of regular food and fruit
treatment is elimination of fructose and sucrose

anion-gap metabolic acidosis
hypo or hyperglycemia
large ketones in urine
mild to severe hyperammonemia
restric amino acids, avoid protein
carnitine is detoxifying

defect in glycine cleavage
profound deterioration of CNS in neonatal period
seizures, lethargy, coma
measure glycine in both plasma and CSF
EEG show burst suppression pattern
no treatment available

3 types and transient neonatal
increased risk of hepatocellular carcinoma
fulminant liver failure
increased succinylacetone levels in plasma and urine
give NTBC and limit phenylalanine and tyrosine

fasting hypoketotic hypoglycemia
fasting encephalopathy
confirmed by plasma and urinary acylcarnitine profile
long-term avoidance of fasting
acute management with glucose infusion

macrocephaly, dystonia, enlarged subdural fluid spaces
recurrent episodes of liver dysfunction with metabolic acidosis
hyoglycemia, hyperammonemia

defect in the transfer of electrons from flavine-adenin nucleotides
associated with increased risk of cardiomyopathy
renal cysts facial dysmorphism, rocker-bottom feet, hypospadias
hypoglycemia without detosis
sweath feet odor
metabolic acidosis

cerebrohepatorena syndrome
high forehead, flat orbital ridges, widely open fontanelles
hepatomegaly, hypotonia, seizures, migration disorders of brain
increased VLC fatty acids in plasma

glucose-6-phosphate deficiency
liver, kidney, platelets, bones
hypoglycemica, lactic acidosis
doll-like face
hepatomegaly
hypotonia, increased uric acid
treat with cornstarch and frequent meals

alpha-glucosidase (lysosomal) deficiency
liver, skeletal muscle, cardiac muscle, peripheral nerves
profound hypotonia, enlarged tongue, cardiomegaly with short PR
enzyme replacement available, otherwise death in first year

debranching enzyme deficiency
liver, skeletal and cardiac muscle
hypoglycemia, ketosis
no lactic acidosis
normal uric acid
muscle weakness

branching enzyme deficiency
liver, skeletal and cardiac muscle, CNS
FTT, liver cirrhosis, cardiomyopathy
hypotonia, muscle weakness
absent DTRs

muscle phosphorylase deficiency
skeletal muscle
exercise-induced rhabdomyolysis
muscle weekness beginningin adolescence
sucrose supplementation may be helpful 

liver glycogen phosphoryase deficiency
liver
mild hypoglycemia and ketosis,
hepatomegaly

Muscle phosphofructokinase deficiency
skeletal muscle
exercise induced rhabdomyolysis
muscle weakness beginning in adolescence
avoid strenuous exercise

phosphoryase kinase deficiency
liver
hypoglycemia, ketosis
no lactic acidosis
normal uric acid
hepatomegaly
good prognosis

alpha-L-iduronidase deficiency
coarse facies, cornieal clouding, neurodegeneration
dysstosis multiplex
hepatosplenomegaly
abnormal glycosaminoglycans in urine

iduronate-2-sulfatase deficiency
mild dwarfism, coarse facial features
macrocephaly
no corneal opacities, hepatosplenomegaly
neurodegeneration
dermatan and heparan sulfate in urine

heparan N-sulfatase deficiency
marked overactivity
destructive tendancies
sleep disturbances
visceromegaly, mild corneal clouding
claw hands
heparan sulfate in urine

N-acetygalactosamine-6-sulfatase deficiency
short trunked dwarfism
mild coarse features
corneal clouding
restrcitive lung disease
dysostosis multiplex
normal intelligence
chondroitin 6-sulfate and keratan sulfate in urine

N-acetylgalactomsamine-4-sulfatase deficiency
short-trunked dwarfism
corneal clouding,
infantile cardiomyopathy
hepatosplenomegaly
dysostosis multiplex
claw-hand
normal intelligence
dermatan sulfate in urine

beta-glucuronidase deficiency
short stature
MR, coarse facial features
variable degree of corneal clouding
visceromegaly
anterior beaking of vertebrae
coarse metachromatic granules in WBCs
dermatan, heparan sulfate, chondroitin in urine

glucocerebrosidase deficiency
accumulation of Gaucher cells at the corneoscleral limbus
hepatosplenomegaly
osteolytic lesions
anemia, thrombocytopenia
increased risk of pathologic fractures
enzyme replacement available

sphingomyelinase deficiency
more common Ashkenazi Jews
hypotonia, hyperreflexia
cherry-red spots
hepatosplenomegaly
FTT, loss of CNS function
foam cells in multiple organs

sphingomyelinase defiency
most common among Ashkanazi Jews
visceral form has no neurolgic manifestations
hepatosplenomegaly and cherry-red spots , less common
frequent respiratory infections
large vacuolated foam cells on bone marrow biopsy
increased LDH, trigs and decreased HDL

intracellular accumulation of cholesterol
highly variable phenotype
vertical supranuclear gaze palsy
hepatosplenomegaly
hypotonia
developmental delay
cerebellar ataxia
MR
Foam cells on bone marrow biopsy

hexosaminidase A deficiency
more common among Ashkenazi Jews and French Canadian
infantile form is fatal by age five
cherry-red spots and blindness
increased startle response
hyperacusis, hypotonia, poor head control
GM1-ganglioside accumulation

arylsulfatase A deficiency
variable age of onset
adult onset may present as psychiatric illness
optic atrophy
biliary tract abnormalities
hypotonia, seizures, loss of neuro function, progressive polyneuropathy
increased protein in CSF
decreased arysulfatase A activity in urine, WBCs and fibroblasts
increased urinary sulfatide excretion

alpha-galactosidase deficiency
delayed puberty
carrier females affected variably
whorl-like corneal dystrophy
CAD and cardiomyopathy
renal failure
autonomic dysfunction, acroparesthesia, increased risk of stroke
lipid laden macrophages in bone marrow

beta-galactosidase deficiency
four clinical forms--infantile, late infantile, juvenile, adult
FTT, optic atrophy, blindness
hyperirritability, mental deterioration, neurodegeneration, hypertonicity, seizures
diffuse cerebral atrophy on CT and MRI
decreased nerve conduction velocity
increased protein in CSF