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VACTERL
- Vertebral anomalies
- Anus imperforate/Atresia
- Cardiac anomalies
- TracheoEsophageal fistula
- Renal and/or Radial anomalies
- Limb anomalies
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Mode of inheritance of Huntington's disease
AD 4p
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Mode of inheritance of Adult Polycystic Kidney Disease
AD 16p
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Mode of inheritance of Neurofibromatosis NF
AD 17
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Mode of inheritance of Vestibular schwannoma NF2
AD 22q
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Mode of inheritance of Protein C deficiency
AD 2p
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Mode of inheritance of Myotonic dystrophy
AD 19q
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Mode of inheritance of Familial retinoblastoma
AD 13q
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Mode of inheritance of von Willebrand's disease
AD 12
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Mode of inheritance of Tuberous sclerosis
- AD 9 and 16
- tuberin and hamartin genes
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Mode of inheritance of Marfan syndrome
AD 15q
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Mode of inheritance of Achondroplasia
- AD 4p
- 80-90% new mutations
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Mode of inheritance of Hereditary spherocytosis
AD spectin deficiency
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Mode of inheritance of Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease)
AD
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Mode of inheritance of Peutz-Jeghers syndrome
- AD
- GI hamartomas
- mucocutaneous pigment
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Mode of inheritance of PKU
AR 12q
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Mode of inheritance of Sickle cell anemia
AR 11
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Mode of inheritance of Congenital adrenal hyperplasia
AR 6p
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Mode of inheritance of Cystic fibrosis
AR 7q
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Mode of inheritance of Gaucher's disease
AR 1q
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Mode of inheritance of Tay-Sachs disease
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Mode of inheritance of Galactosemia
AR 9p
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Mode of inheritance of Wilson's disease
AR 13q
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Mode of inheritance of Fanconi's anemia
- AR
- chromosomal breakage
- absent thumbs
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Mode of inheritance of Duchenne muscular dystrophy
- X-linked recessive
- dystrophin gene
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Mode of inheritance of Lesch-Nyhan syndrome
- X-linked recessive
- hypoxanthine-phosphoribosyl transferase
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Mode of inheritance of Ornithine transcarbamoylase OTC deficiency
X-linked recessive
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Mode of inheritance of Hemophilia A and B
X-linked recessive
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Mode of inheritance of Fragile X syndrome
X-linked recessive
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Mode of inheritance of Chronic granulomatous disease
- X-linked recessive
- recurrent infections
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Mode of inheritance of G6PD deficiency
- X-linked recessive
- oxidant-induced hemolysis
- 10% of AA males
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Mode of inheritance of Color blindness
X-linked recessive
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Mode of inheritance of Leber's hereditary optic neuropathy
- Mitochondrial
- homoplasmic (cells contain only abnormal mtDNA)
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Mode of inheritance of NARP
- Mitochondrial
- Leigh's disease
- Neuropathy, Ataxia, Retinitis Pigmentosa, developmental delay, mental retardation, lactic acidosis
- heteroplasmic
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Mode of inheritance of MELAS
- Mitochondrial
- Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike episodes
- may have DM
- heteroplasmic
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Mode of inheritance of MERRF
- Mitochondrial
- Myoclonic Epilepsy Ragged Red Fibers
- ataxia
- sensorineural deafness
- heteroplasmic
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Mode of inheritance of Kearns-Sayre syndrome
- Mitochondrial
- progressive external ophthalmoplegia, heart block, retinal pigmentation
- heteroplasmic with sporadic mutations
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15q 11-q13 father
- Prader-Willi
- hypotonia, FTT in infancy
- hyperphagia, small hands and feet
- MR
- hypogonadism
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15q 11-q13 mother
- Angelman's syndrome
- absent speech
- prominent mandible, wide mouth, widely spaced teeth, strabismus
- microcephaly, seizures, MR, laughter, outbursts, ataxia
- happy puppet
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SGA, narrow nose, hypoplastic nasal alae
narrow bifrontal diameter
short sternum
congenital heart disease
overlapping fingers
rocker-bottom feet
Trisomy 18
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postnatal growth retardation
scalp defects
cleft lip and palate
congenital heart disease
renal anomalies
omphalocele
Trisomy 13
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no increased risk with maternal age
short stature
bicuspid aortic valve
coarctation of the aorta
lymphedema in infancy
Turner's 45 XO
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many variants
no signs in prepubertal boys
postpubertal boys infertility, mild MR, gynecomastia, long limbs
Klinefelter syndrome 47 XXYY
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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
- DeGeorge syndrome
- 22q11.2, AD
- Velocardiofacial syndrome
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microcephaly
cat cry in the newborn period
epicanthanl folds
cardiac defect
severe pychomotor retardation
- Cri-du-Chat syndrome
- deletion 5p
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short stature, periorbital fullness/puffy
neonatal hypercalcemia
stellate iris, antevered nares, thick lips, microdontia
supravalvular aortic stenosis, bicuspid aorta
pectus excavatum
nephrocacinosis
MR
- Williams-Beuren syndrome
- deletion 7q, AD
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brachycephaly, broad face
hearing loss
cardiac and renal abnormalities
MR, behavioral abnormalitis, self-destructive
sleep distrubances
decreased pain sensation
- Smith-Magenis syndrome
- deletion 17p
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triangular face
anterior chamber anomalies
PPS, ASD, VSD
cholesatsis with intrahepatic duct deficiency
vertebral anomalies
mild MR
hypercholesterolemia, hypertriglyceridemia, abnormal LFTs
- Alagille syndrom
- AD
- jagged-1 gene 20p12 mutation
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CHARGE
- Coloboma
- Heart defect
- Atresia choanae
- Retarded growth/abnormal CNS development
- Genital anomalies/hypogonadism
- Ear anomalies/deafness
- AD mutations CHD7
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frontal bossing, megalencephaly
risk of foramen magnum stenosis
recurrent OM
conductive hearing loss
OSA
hydrocephalus
rhizomelia
- Achondroplasia
- AD
- mutation in fibroblast growth factor
- 80% new mutations
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4 types of OI and mode of inheritance
- Type I blue sclerae, brittle bones
- Type II lethal perinatal period
- Type III progressive structural bone defects
- Type IV normal sclerae, brittle bones, tooth anomalies
- AD
- protein type I collagen
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exophthalmos, macroglossia, hypoglycemia, macrosomia
hemihypertrophy, cardiomegaly, renal abnormalities
gonadoblastoma
- Beckwith-Wiedemann syndrome
- 11p15.5 duplication or deletion
- uniparental disomy
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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
- Noonan syndrome
- AD, one of four gene mutations
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microcephaly, long philtrum
hearing loss
synophrys, long, curly eyelashes
wide spaced teeth
limb abnormalities
cutis marmorata, hirsutism
- Cornelia de Lange syndrome
- AD
- mutation in nipped-B-like gene
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postnatal growth retardation
microcephaly
beaked nose
cardiac abnormalities
broad thumbs with radial angulation, broad great toes
MR
increased risk of tumors, esp of head
- Rubinstein-Taybi syndrome
- AD
- mutation in CREB-binding protein gene
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large cutaneous hemangiomata
lymphangioma
asymmetric limb hypertrophy
macrodactyly
MR
Kasabach-Merritt syndrome
Klippel-Trenaunay-Weber syndrome
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SGA lateral asymmetry and normal HC
cardiac defects
fifth-finger clinodactyly
cafe au lait spots
MR
risk of neoplasm
Russell-Silver syndrome
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short stature
microcephaly, micrognathia
hypotelorism
ptosis, cataracts
VSD, ASD, coarc
micropenis
syndactyly of the second and third toes
MR, seizures, hypotonia
low cholesterol
- Smith-Lemli-Opitz syndrome
- AR
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Lisch nodules
optic glioma
hypertension, renal artery stenosis
cafe au lait spots, axillary freckling, plexiform neurofibromas
learning disabilitiss
increased risk of neoplams
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achromatic retinal patches
cardiac rhabdomyoma
facial angiofibroma
ash leaf macules, shagreen patch, subcutaneous nodules
seizures, MR
intracranial calcifications
- Tuberous Sclerosis
- AD
- mutations in the hamartin gene or the tuberin gene
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famililial cancer syndrome
4 types
- von Hippel-Lindau syndrome
- AD
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hemangiomata ophthalmic branch trigeminal
MR
seizures
Sturge Weber syndrome
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short stature, cutaneous telangiectasia
cerebellar ataxia
decreased or absent DTRs
thymic hypoplasia
hypersensitivity to ionizing radiation
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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
- MSUD
- AR
- branched chain ketoaciduria
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urine smells of sweaty feet
Isovaleric acidemia
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cat urine
multiple carboxylase deficiency
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musty urine
deficiency of phenylalanine hydroxylase in the liver
severe MR if not treated
blond hair, blue eyes, eczema
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urine smells of rancid butter, rotten cabbage
hypermethioninemia
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urine smells fishy
trimethylaminuria
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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
- galactosemia
- AR
- deficiency of galactos-1-phophate uridyltransferase
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marfanoid habitus
dislocated lense
MR
AV thrombosis
- Homocystinuria
- AR
- deficiency of cystathionine beta-synthetase
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3 causes of hyperammonemia first 24 hours
- Transient hyperammonemia of the newborn
- Pyruvate dehydraogenase deficiency
- Electron transport defects
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Causes of hyperammonemia >24 hours
- With acidosis:
- Organic acidemias:
- methylmalonic acidemia MMA,
- Proprionic acidemia PA
- Without acidosis:
- Urea cycle defects:
- carbamoyl phosphate synthetase deficiency CPSD,
- ornithine transcarbamoylas deficiency OTCD,
- argininosuccinic acid lyase deficiency ALD
- argininosuccinic acid synthetase deficiency ASD
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Causes of positive reducing substances
- glucosuria (DM or renal tubular dysfunction)
- galactosemia
- fructosuria
- alkaptonuria
- drugs
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emesis, hypoglycemia, liver and kidney disease
symptoms arise after introduction of regular food and fruit
treatment is elimination of fructose and sucrose
Hereditary frutose intolerence
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anion-gap metabolic acidosis
hypo or hyperglycemia
large ketones in urine
mild to severe hyperammonemia
restric amino acids, avoid protein
carnitine is detoxifying
- Organic acidurias
- MMA methylmalonic acidemia
- PPA propionic acidemia
- IVA isovaleric acidemia
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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
- Nonketotic hyperglycinemia
- AR
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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
tyrosinemia
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fasting hypoketotic hypoglycemia
fasting encephalopathy
confirmed by plasma and urinary acylcarnitine profile
long-term avoidance of fasting
acute management with glucose infusion
- Fatty Acid oxidaiton disorders
- SCAD, MCAD, VLCAD
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macrocephaly, dystonia, enlarged subdural fluid spaces
recurrent episodes of liver dysfunction with metabolic acidosis
hyoglycemia, hyperammonemia
Glutaric aciduria Type I
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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
Glutaric Aciduria Type II
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cerebrohepatorena syndrome
high forehead, flat orbital ridges, widely open fontanelles
hepatomegaly, hypotonia, seizures, migration disorders of brain
increased VLC fatty acids in plasma
- Peroxisomal diseases
- Zellweger syndrome
- AR
- others are Refsum, adrenoleukodystrophy, rhizomelic chondrodysplasia punctata
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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
- Type I glycogen storage disease
- von Gierke
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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
- Type II glycogen storage disease
- Pompe
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debranching enzyme deficiency
liver, skeletal and cardiac muscle
hypoglycemia, ketosis
no lactic acidosis
normal uric acid
muscle weakness
- Type III glycogen storage disease
- Forbes'
- Cori's
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branching enzyme deficiency
liver, skeletal and cardiac muscle, CNS
FTT, liver cirrhosis, cardiomyopathy
hypotonia, muscle weakness
absent DTRs
- Type IV glycogen storage disease
- Andersen's disease
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muscle phosphorylase deficiency
skeletal muscle
exercise-induced rhabdomyolysis
muscle weekness beginningin adolescence
sucrose supplementation may be helpful
- Type V glycogen storage disease
- McArdle's
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liver glycogen phosphoryase deficiency
liver
mild hypoglycemia and ketosis,
hepatomegaly
- Type VI glycogen storage disease
- Hers'
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Muscle phosphofructokinase deficiency
skeletal muscle
exercise induced rhabdomyolysis
muscle weakness beginning in adolescence
avoid strenuous exercise
- Type VII glycogen storage disease
- Tarui
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phosphoryase kinase deficiency
liver
hypoglycemia, ketosis
no lactic acidosis
normal uric acid
hepatomegaly
good prognosis
Type IX glycogen storage disease
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alpha-L-iduronidase deficiency
coarse facies, cornieal clouding, neurodegeneration
dysstosis multiplex
hepatosplenomegaly
abnormal glycosaminoglycans in urine
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iduronate-2-sulfatase deficiency
mild dwarfism, coarse facial features
macrocephaly
no corneal opacities, hepatosplenomegaly
neurodegeneration
dermatan and heparan sulfate in urine
- MPS II
- Hunter
- X-linked recessive
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heparan N-sulfatase deficiency
marked overactivity
destructive tendancies
sleep disturbances
visceromegaly, mild corneal clouding
claw hands
heparan sulfate in urine
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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
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N-acetylgalactomsamine-4-sulfatase deficiency
short-trunked dwarfism
corneal clouding,
infantile cardiomyopathy
hepatosplenomegaly
dysostosis multiplex
claw-hand
normal intelligence
dermatan sulfate in urine
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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
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glucocerebrosidase deficiency
accumulation of Gaucher cells at the corneoscleral limbus
hepatosplenomegaly
osteolytic lesions
anemia, thrombocytopenia
increased risk of pathologic fractures
enzyme replacement available
- Type I lysosomal storage disease
- Gaucher's
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sphingomyelinase deficiency
more common Ashkenazi Jews
hypotonia, hyperreflexia
cherry-red spots
hepatosplenomegaly
FTT, loss of CNS function
foam cells in multiple organs
- Type A Niemann-Pick
- lysosomal storage disease
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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
- Type B Niemann-Pick
- lysosomal storage disease
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intracellular accumulation of cholesterol
highly variable phenotype
vertical supranuclear gaze palsy
hepatosplenomegaly
hypotonia
developmental delay
cerebellar ataxia
MR
Foam cells on bone marrow biopsy
- Type C Niemann-Pick
- lysosomal storage disease
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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
- GM2 gangliosidosis
- Tay-Sachs disease
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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
Metachromatic leukodystrophy
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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
- Fabry's disease
- X-linked recessive
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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
Krabbe's disease
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