A comprehensive list of

syndromes and genetic diseases

encountered during Step 1 and
2CK prep

Collection of
syndromes
Step 1 & 2
Contents
ADRENO-LEUKO-DYSTROPHY............................................................................................................................................... 7

ALAGILLE SYNDROME.......................................................................................................................................................... 7

ALPORT’S............................................................................................................................................................................. 7

ANGELMAN SYNDROME...................................................................................................................................................... 8

ASPERGER........................................................................................................................................................................... 8

BARTH SYNDROME.............................................................................................................................................................. 9

BARTTER SYNDROME........................................................................................................................................................... 9

BECKWITH-WIEDMANN..................................................................................................................................................... 10

BEHCET SYNDROME........................................................................................................................................................... 10

BENEDIKT SYNDROME....................................................................................................................................................... 10

BERNARD SOULIER SYNDROME.......................................................................................................................................... 11

BLOOM SYNDROME........................................................................................................................................................... 11

BOERHAAVE SYNDROME................................................................................................................................................... 12

BRUGADA SYNDROME....................................................................................................................................................... 12

BUDD-CHIARI..................................................................................................................................................................... 13

CAPLAN SYNDROME.......................................................................................................................................................... 13

CAUDAL REGRESSION SYNDROME..................................................................................................................................... 13

CHARCOT-MARIE-TOOTH DISEASE..................................................................................................................................... 13

CHARGE............................................................................................................................................................................. 14

CHEDIAK HIGASHI.............................................................................................................................................................. 15

CHURG STRAUSS................................................................................................................................................................ 15

CONN’S.............................................................................................................................................................................. 15

CORI DISEASE..................................................................................................................................................................... 16

COWDEN SYNDROME........................................................................................................................................................ 16

CRI-DU-CHAT..................................................................................................................................................................... 17

CRIGGLER NAJJAR.............................................................................................................................................................. 17

DENYS-DRASH SYNDROME................................................................................................................................................. 17

DIAMOND-BLACKFAN........................................................................................................................................................ 18

ANEMIA............................................................................................................................................................................. 18

DIGEORGE......................................................................................................................................................................... 18

DOBIN-JOHNSON............................................................................................................................................................... 19

DOWN............................................................................................................................................................................... 19
DRESS SYNDROME............................................................................................................................................................. 20

DRESSLER.......................................................................................................................................................................... 20

DUBIN-JOHNSON SYNDROME............................................................................................................................................ 20

EDWARD’S......................................................................................................................................................................... 20

EHLERS-DANLOS................................................................................................................................................................ 21

SYNDROME....................................................................................................................................................................... 21

EISENMENGER’S................................................................................................................................................................ 22

FABRY................................................................................................................................................................................ 22

FANCONI ANEMIA............................................................................................................................................................. 22

FANCONI SYNDROME........................................................................................................................................................ 23

FELTY SYNDROME.............................................................................................................................................................. 23

FETAL ALCOHOL SYNDROME.............................................................................................................................................. 23

FETAL HYDANTOIN SYNDROME.......................................................................................................................................... 23

FRAGILE X.......................................................................................................................................................................... 24

FRIEDREICH ATAXIA........................................................................................................................................................... 24

GARDNER’S SYNDROME..................................................................................................................................................... 24

GAUCHER.......................................................................................................................................................................... 25

GILBERT’S.......................................................................................................................................................................... 25

GITELMAN SYNDROME...................................................................................................................................................... 26

GOOD PASTURE................................................................................................................................................................. 26

GUILLAIN-BARRE SYNDROME............................................................................................................................................. 26

HARTNUP DISEASE............................................................................................................................................................. 26
HELLP................................................................................................................................................................................ 27

HEMOLYTIC UREMIC.......................................................................................................................................................... 28

HERS DISEASE.................................................................................................................................................................... 28

HOMOCYSTINURIA............................................................................................................................................................ 28

HORNER SYNDROME......................................................................................................................................................... 29

HURLER............................................................................................................................................................................. 29

I-CELL DISEASE................................................................................................................................................................... 29

JERVELL-LANGE-NIELSEN.................................................................................................................................................... 31

KALLMANN........................................................................................................................................................................ 31

KARTAGENER SYNDROME.................................................................................................................................................. 32

KLINEFELTER...................................................................................................................................................................... 33

KLUVER-BUCY SYNDROME................................................................................................................................................. 33

KRABBE............................................................................................................................................................................. 34
LAMBERT-EATON............................................................................................................................................................... 34

LARON SYNDROME............................................................................................................................................................ 34

LEBER HEREDITARY OPTIC NEUROPATHY........................................................................................................................... 35

LEGG-CALVÉ -PERTHES DISEASE......................................................................................................................................... 35

LENNOX-GASTAUT............................................................................................................................................................. 36

LERICHE SYNDROME.......................................................................................................................................................... 36

LESCH-NYHAN.................................................................................................................................................................... 36

LIDDLE SYNDROME............................................................................................................................................................ 36

LI-FRAUMENI SYNDROME.................................................................................................................................................. 37

LUTEMBACHER SYNDROME............................................................................................................................................... 38

LYNCH SYNDROME............................................................................................................................................................ 38

MALLORY-WEISS SYNDROME............................................................................................................................................. 39

MARFAN............................................................................................................................................................................ 39

MCARDLE DISEASE............................................................................................................................................................. 40

MCCUNE-ALBRIGHT........................................................................................................................................................... 41

MEIGS SYNDROME............................................................................................................................................................. 42

MELAS SYNDROME............................................................................................................................................................ 42

MEN 1............................................................................................................................................................................... 43

(PREVIOUSLY KNOWN AS WERMER SYNDROME)............................................................................................................... 43

MEN 2A............................................................................................................................................................................. 43

MEN 2B............................................................................................................................................................................. 43

MENKES DISEASE............................................................................................................................................................... 44
MERRF SYNDROME............................................................................................................................................................ 45

MUNCHAUSEN................................................................................................................................................................... 45

NEIMANN-PICK.................................................................................................................................................................. 45

NELSON SYNDROME.......................................................................................................................................................... 45

NEUROFIBROMATOSIS TYPE 1............................................................................................................................................ 46

NEUROFIBROMATOSIS TYPE 2............................................................................................................................................ 47

OGILVIE SYNDROME.......................................................................................................................................................... 47

ORTNER SYNDROME.......................................................................................................................................................... 47

OSLER-WEBER-RENDU SYNDROME.................................................................................................................................... 47

PARINAUD......................................................................................................................................................................... 48

PATAU SYNDROME............................................................................................................................................................ 48

PEUTZ-JEGHERS................................................................................................................................................................. 49

PIERRE ROBIN SEQUENCE................................................................................................................................................... 49

POMPE’S........................................................................................................................................................................... 49

POTTER SEQUENCE............................................................................................................................................................ 50

PRADER-WILLI................................................................................................................................................................... 51

PRUNE BELLY..................................................................................................................................................................... 51

RAMSAY HUNT SYNDROME............................................................................................................................................... 51

REFSUM DISEASE............................................................................................................................................................... 52

REYE.................................................................................................................................................................................. 52

ROMANO-WARD............................................................................................................................................................... 52

ROTOR’S SYNDROME......................................................................................................................................................... 52

SAME SYNDROME.............................................................................................................................................................. 53

SANDIFER.......................................................................................................................................................................... 54

SJOGREN’S......................................................................................................................................................................... 54

STEWART-TREVES SYNDROME........................................................................................................................................... 55

STURGE-WEBER................................................................................................................................................................. 55

SWYER............................................................................................................................................................................... 56

TAY-SACHS........................................................................................................................................................................ 56

THYROID HORMONE RESISTANCE SYNDROME................................................................................................................... 56

TREACHER COLLINS SYNDROME......................................................................................................................................... 57

TROUSSEAU SYNDROME.................................................................................................................................................... 58

TUBEROUS SCLEROSIS........................................................................................................................................................ 58

TURNER’S.......................................................................................................................................................................... 59

VACTERL............................................................................................................................................................................ 59
VON RECKLINGHAUSEN..................................................................................................................................................... 60

VON-GIERKE’S.................................................................................................................................................................... 60

VON-HIPPEL-LINDAU.......................................................................................................................................................... 61

WALLENBERG SYNDROME................................................................................................................................................. 62

WATERHOUSE FRIDERICHSEN............................................................................................................................................ 62

WEBER’S SYNDROME......................................................................................................................................................... 62

WERDNIG-HOFFMANN DISEASE......................................................................................................................................... 63

WERNICKE-KORSAKOFF..................................................................................................................................................... 63

WILLIAM’S......................................................................................................................................................................... 64

WISKOTT-ALDRICH............................................................................................................................................................. 64

WOLFF-PARKINSON_WHITE............................................................................................................................................... 64

ZELLWEGER SYNDROME..................................................................................................................................................... 64

ZOLLINGER-ELLISON........................................................................................................................................................... 65
Collection of Syndromes
  X-linked recessive disorder
Adreno- of β-oxidation due to
leuko- mutation in ABCD1 gene >>
dystrophy
VLCFAs defective transport
to peroxisomes and
accumulation in adrenal
gland, white matter of brain
and testes.
 Progressive disease that can
lead to adrenal crisis,
neurologic deterioration,
come and death.
Associated with TOF
Alagille
syndrome
X-linked dominant defect in
Alport’s collagen type IV synthesis
(present in basement
membranes, lens and
cochlea) due to COL4A5
gene mutation
Sensorineural hearing loss
Ocular abnormality
(cataracts, lens dislocation)
Hematuria (nephritic
syndrome)
Progressive renal
insufficiency
EM: basket weave
appearance
 Absent maternal 15q11-
Angelman q13
syndrome Paternal copy of UBE3A is
imprinted and loss of active
maternal copy
Frequent smiling/laughter
Intellectual disability
Seizures
Ataxia

Asperger
Exclusive in males
Barth Due to mutations affecting
syndrome mitochondria
Dilated cardiomyopathy
Skeletal myopathy
Neutropenia and recurrent
infections
Short stature
 Autosomal recessive
Bartter Present similar to loop
syndrome diuretics effect
Reabsorption defect in the
thick ascending loop of
Henle affecting Na/K/2Cl
transporter
Leads to :
-Metabolic alkalosis
-Hypokalemia
-Hypercalciuria
Disregulation of imprinted
Beckwith- gene expression on 11p15
Wiedmann WT2 mutation
Macroglossia
Hemi-hyperplasia
Medial abdominal wall
defects (omphalocele,
umbilical hernia)
Increased risk for Wilm’s
tumor & Hepatoblastoma
 Small vessel vasculitis
Behcet 
syndrome
Due to midbrain damage
Benedikt affecting oculomotor nerve,
syndrome medial lemniscus and red
nucleus
Leads to :
1-Ipsilateral oculomotor
palsy
2-Contralateral loss of
vibration and position sense
3-Contralateral
ataxia/tremors
Hereditary deficiency of GP
Bernard Ib receptors
Soulier Characterized by:
syndrome
1)Thrombo-cytopenia
2)Enlarged platelets
3)Muco-cutaneous bleeding
 Autosomal recessive
Bloom disorder caused by BLM
syndrome gene mutation which results
in helicase deficiency
Premature aging due to
shortened telomeres
Growth retardation and
short stature
Infertility
Predisposition to
malignancy
Facial anomalies
(microcephaly)
Photosensitive rash
Immuno-deficiency and
recurrent infections
Spontaneous esophageal
Boerhaave perforation
Syndrome Full thickness transmural
tear
With forceful vomiting
 Autosomal dominant
Brugada Mutation in sodium or L-
syndrome type Ca channels
Characteristic ECG changes:
pseudo RBBB, ST elevation in
V1-V3
Increased risk of ventricular
arrhythmias and SCD
Hepatic vein thrombosis
Budd-Chiari 
Seropositive rheumatoid
Caplan arthritis + rheumatoid
syndrome nodules in the lung >>
rheumatoid pneumoconiosis
 Rare malformation of sacral
Caudal agenesis
regression  Occurs almost exclusively in
syndrome
IODMs
 Defects can include:
incomplete development of
sacrum, lumbar vertebrae
and lower extremities
 AKA hereditary motor and
Charcot- sensory neuropathy
Marie- Due to mutation of the
Tooth
genes responsible for
disease
proteins involved in the
structure and function of
PNs and myelin sheath
Typically autosomal
dominant
Most common type is
CMT1A is caused by PMP22
gene duplication
Patients frequently present
with:
1. distal muscle weakness
2. Sensory loss
3. Atrophy of the calf
muscles >> stork leg
deformity, pes cavus and
hammer toe
 Coloboma
CHARGE Heart defects
Atresia of choana
Retardation of growth/
development
Genitourinary anomalies
Ear abnormalities/ deafness

Chediak
Higashi
Eosinophilic granulomatosis
Churg with polyangiitis
Strauss Allergic rhinitis
Late onset asthma
Peripheral eosinophilia
Mononeuritis multiplex due
to involvement of epineural
vessels of peripheral nerves
Aldosterone producing
Conn’s adrenal adenoma
Hypokalemia
Muscle weakness
Hypertension
Low renin activity
No severe hypernatremia
due to aldosterone escape
mechanism
 Glycogen storage disease
Cori disease type III
Milder form of Von Gierke
with normal blood lactate
level
Debranching enzyme α-1-6
glucosidase deficiency
Leads to hepatomegaly and
hypotonia due to
accumulation of limit
dextrin-like structures in
cytosol of liver and muscles
Cardiomyopathy and
hypertrophy may occur
Gluconeogenesis is intact

Cowden
syndrome
5p deletion
Cri-du-chat Cat-like cry
Microcephaly
Protruding metopic suture
Short stature
Hypotonia
Hypertelorism
Wide flat nasal bridge
Intellectual disability
 Absent enzyme UDP-
Criggler glucuronyl transferase
Najjar Present early in life
Require liver
transplantation
Loss of function mutation in
Denys- WT1 gene on chromosome
Drash 11
syndrome
Wilm’s tumor
Diffuse mesangial sclerosis
(early-onset nephrotic
syndrome)
Dysgenesis of gonads (male
pseudo hermaphroditism)
Rapid onset anemia within
Diamond- the 1st year of life
Blackfan Macrocytic non-
anemia megaloblastic anemia
Intrinsic defect in erythroid
progenitor cells
↑% of HbF but ↓total Hb
Associated with:
-Short stature
-Craniofacial abnormalities
-Upper extremity
malformations like
triphalangeal thumbs
 22q11.2 deletion
DiGeorge Thymic aplasia (T-cell
deficiency)
Hypoparathyroidism >>
hypocalcemia
Associated with: tetralogy
of Fallot, truncus arteriosus,
TGA

Dobin-
Johnson
Trisomy 21
Down Transverse palmar crease
Upward slanting eyes
Brush field spots
Epicanthal fold
Intestinal atresia
Cardiac defects (the most
common is endocardial
cushion defect)
Hypotonia
Mental retardation
 Stands for: drug reaction
DRESS with eosinophilia and
syndrome systemic symptoms
Idiosyncratic reaction to
some medications as
phenytoin
Post-MI pericarditis
Dressler Fever and pleuritic chest
pain >2 weeks after MI
Pericardial friction rub
Direct hyper-bilirubinemia
Dubin- Normal AST,ALT,ALP
Johnson
Due to absence of
syndrome
multidrug resistance protein
2

Trisomy 18
Edward’s Clenched fist
Rocker bottom feet
IUGR
Heart defects
Microcephaly
Micrognathia
Prominent occiput
 Common mutations include
Ehlers- deficiency of lysyl
Danlos hydroxylase and procollagen
Syndrome peptidase enzymes
responsible for collagen
synthesis
Types:
1. Hyper-mobility type
(joint instability)
2. Classic type: due to
COL5A1, COL5A2 mutations
(skin and joint symptoms)
3. Vascular type: due to
COL3A1 mutation >> life
threatening
Skin hyper extensibility
Joint hyper mobility
Tissue fragility
Poor wound healing
Lens dislocation
Easy bruising
Mitral valve prolapse
 
Eisenmenge
r’s
Lysosomal storage disease,
Fabry XR
Deficiency in α-
galactosidase A enzyme
leads to accumulation of
ceramide trihexoside in
cardiac myocytes, smooth
muscles of blood vessels,
glomerular and DCT cells and
autonomic and dorsal root
ganglia
Early disease: triad of
peripheral neuropathy,
angiokeratomas and
hypohidrosis
Late disease:
cardiomyopathy (LVH, HF)
and progressive renal failure
 Inherited aplastic anemia,
Fanconi AR or X-linked
anemia DNA repair defect causing
bone marrow failure
Associated with:
-Short stature
-Café au lait spots
-Thumb/radial defects
-Heart, renal and eye
abnormalities
-Increased incidence of
malignancies (AML,
myelodysplastic syndrome,
SCC of head/neck or vulva)
Kidney disease
Fanconi
syndrome
Long standing RA with
Felty extra-articular
syndrome manifestations
Neutropenia
Splenomegaly
 
Fetal
alcohol
syndrome

Fetal
hydantoin
syndrome
Most common cause of
Fragile X inherited intellectual
disability
Macroorchidism
Prominent forehead
Mutation in frataxin, a
Friedreich mitochondrial protein
ataxia important in iron
homeostasis and respiratory
function
Characterized by
spinocerebellar
degeneration
Associated with
hypertrophic
cardiomyopathy
 
Gardner’s
Syndrome
Inherited lysosomal storage
Gaucher disease, AR
Most common among
Ashkenazi Jews
Deficiency in
glucocerebrosidase enzyme
leads to accumulation of
glucocerebroside in bone,
liver and spleen
Diffuse painful lytic bone
lesions, osteoporosis , bone
crisis similar to SCD
Hepatosplenomegaly
Avascular necrosis of femur
Delayed puberty and
growth
Gaucher cells > lipid laden
macrophages resembling
crumbled tissue paper
 More common in males
Gilbert’s Mutation in UGT1A1 gene
leads to ↓ bilirubin
glucuronidation
Mild enzymatic deficiency
of UDP-glucuronyl
transferase
↑ unconjugated bilirubin
Provoked by stress
Normal Labs
No specific treatment
Autosomal recessive
Gitelman Presents similar to thiazide
syndrome diuretics effect
Reabsorption defect in DCT
affecting Na/Cl channel
Leads to:
-Metabolic alkalosis
-Hypokalemia
-Hypocalciuria
-Hypo magnesemia
 Anti-basement membrane
Good Abs
Pasture Lung & Kidney disease
Endoneural inflammatory
Guillain- infiltration is characteristic
Barre Ascending flaccid paralysis
Syndrome
Hyporeflexia
Autosomal recessive
Hartnup disorder caused by
disease inactivating mutations
affecting the neutral amino
acids transporters
Leads to impaired transport
of neutral amino acids
particularly tryptophan in
small intestine and proximal
kidney tubule
Presents with neutral
amino aciduria, pellagra-like
symptoms and cerebellar
ataxia in early childhood that
becomes less severe with
increasing age
 Hemolysis
HELLP Elevated liver enzymes
Low platelet count
Present with:
*Preeclampsia
*RUQ pain
*N/V

Hemolytic
uremic
Liver glycogen
Hers phosphorylase deficiency
disease Present in early childhood
with mild hypoglycemia,
ketosis and hepatomegaly
Doesn’t affect skeletal
muscles
Liver biopsy shows excess
of normally structured
glycogen
 Ectopia lentis
Homocystin Presents at age 3-10
uria
Increased risk of
cerebrovascular accidents
due to increased incidence
of thromboembolic
occlusions
Intellectual disability
Marfanoid habitus
Autosomal recessive
deficiency of cystathionine
beta synthase
Ptosis
Horner Miosis
syndrome
Anhydrosis
Lysosomal storage disease,
Hunter XR
syndrome Deficiency of iduronate-2-
sulfatase enzyme leads to
accumulation of heparan
sulfate and dermatan sulfate
Mild form of Hurler
syndrome but without
corneal clouding
Aggressive behavior
Learning difficulties
Trouble sitting still which
mimics ADHD
 Lysosomal storage disease,
Hurler AR
syndrome Deficiency in α-iduronidase
enzyme leads to
accumulation of heparan
sulfate and dermatan sulfate
Dysostosis multiplex
(characteristic bony defects
due to abnormal bone and
cartilage formation)
Airway problems (tracheal
cartilage abnormalities >>
airway obstruction and sleep
apnea, thick secretions lead
to recurrent ear, sinus and
pulmonary infections)
HSM
Gargoylism (coarse facies)
Developmental delay
Corneal clouding
 Autosomal recessive
I-cell lysosomal storage disease
disease Defect in N-acetyl
glucosaminyl-1-phospho
transferase >> failure of
Golgi to phosphorylate
mannose residues and
↓mannose 6 phosphate on
glycoproteins
Leads to proteins being
secreted extracellularly
rather than delivered to
lysosomes >> ↑plasma level
of lysosomal enzymes
Lysosomes contain
inclusions of undigested
glycolipids and glycosamino-
glycans
Symptoms:
1. Coarse facial features
2. Hypotonia
3. Gingival hyperplasia
4. Clouded corneas
5. Growth failure
6. Motor delay
7. Restricted joint
movements
8. Claw hand deformities
9. Kyphoscoliosis
10. Often fatal in childhood
 Autosomal recessive
Jervell- Congenital long QT
Lange- syndrome
Nielsen
Bilateral sensorineural
hearing loss
Mutation in genes (KCNQ1,
KCNE1) >> decrease in
outward rectifying K current
in phase 3 of cardiac action
potential
Predisposes to torsades de
pointes , VF and SCD
Failure of migration of
Kallmann GnRH neurons from their
origin in olfactory bulb to
hypothalamus
Leads to defective GnRH
production as well as
defective maturation of
olfactory bulb
Mutation in
KAL-1 gene or the fibroblast
growth factor receptor-1
gene
Anosmia
Hypogonadism
More in males than females
5:1
Low GnRH, FSH, LH,
Testosterone
Delayed puberty
 Autosomal recessive
Kartagener disorder
syndrome Immotile cilia syndrome/
Primary ciliary dyskinesia
Triad of :
1-Situs inversus
2-Chronic sinusitis
3-Bronchiectasis
↓male and female fertility
due to immotile sperm and
dysfunctional fallopian tubes
Chronic ear infections
Conductive hearing loss
↓nasal nitric oxide >> used
as a screening test
47,XXY
Klinefelter Primary hypogonadism
Tall stature
Bilateral damage to
Kluver-
 amygdala, rare complication
Bucy of HSV-1 encephalitis
syndrome Hyperphagia
Hyperorality
Hypersexuality
Visual agnosia
Lysosomal storage disease,
Krabbe AR
Deficiency of
galactocerebrosidase
enzyme leads to
accumulation of
galactocerebroside >>
defective myelin synthesis
Damage of
oligodendrocytes leads to
central demyelination
Peripheral neuropathy
Optic atrophy
Globoid cells
Developmental delay
 Neuromuscular junction
Lambert- disease
Eaton Most commonly associated
with small cell lung cancer &
Hodgkin’s lymphoma
It is caused by
autoantibodies against
voltage gated calcium
channels on the presynaptic
membrane causing
decreased release of
acetylcholine

Autosomal recessive
Laron disorder
syndrome Defective GH receptors
↑ GH, ↓ IGF-1
Short stature
Small head circumference
Characteristic facies: saddle
nose, prominent forehead
Delayed skeletal
maturation
Small genitalia
 A rare mitochondrial
Leber disorder
hereditary Cell death in optic nerve
optic
neurons
neuropathy
Lead to bilateral subacute
vision loss in teens/young
adults
Usually permanent
90% in males
Idiopathic osteonecrosis of
Legg-Calvé - the hip
Perthes Occurs in children
disease

Lennox-
Gastaut
Aorto-iliac atherosclerosis
Leriche causing occlusion proximally
syndrome Occlusion affects blood
flow through external iliac
artery >> thigh claudication
and also pudendal and
gluteal branches of internal
iliac artery >> impotence &
gluteal claudication
 HGPRT enzyme def.
Lesch- Hyperuricemia and gout
Nyhan
Self-mutilation
Mental retardation
Extrapyramidal $ (Dystonia)
Autosomal dominant
Liddle Gain of function mutation
syndrome leads to over activity of Na
channels in collecting
tubules >> ↑ Na
reabsorption
Presents similar to hyper
aldosteronism but
aldosterone levels are
almost undetectable in this
case due to inhibition by
increased Na retention
Leads to :
-Metabolic alkalosis
-Hypokalemia
-Hypertension
-↓ aldosterone level
 Syndrome of multiple
Li- malignancies at an early age
Fraumeni SBLA cancer syndrome
syndrome
(sarcoma, breast, leukemia,
adrenal gland tumors)
Mutation in tumor
suppressor gene TP53 leads
to defective P53 protein
This leads to impaired cell
cycle arrest in response to
DNA damage >>
accumulation of damage
leads to malignancy
Mitral stenosis + left to
Lutembach right shunt at atrial level >>
er ASD
syndrome
Hereditary non-polyposis
Lynch colorectal cancer
Syndrome Germ line mutations of
DNA mismatch repair
enzymes, 90% of cases due
to mutations in MLH1 &
MSH2 (other genes involved
include MSH6, PMS2)
Autosomal dominant
disease
Endometrial cancer
Ovarian cancer
Hallmark: cancer cells with
microsatellite instability
 Spontaneous esophageal
Mallory- tear
Weiss Non transmural
Syndrome
With forceful vomiting
Autosomal dominant
Marfan disease
Fibrillin-1 gene mutation
(FBN1)
Associated with cystic
medial necrosis of the aorta
that leads to:
1) aortic dissection
2)aortic valve regurgitation
Mitral valve prolapse is
common
Ectopia lentis
Check P.52 in FA 2019
Glycogen storage disease
McArdle type V
disease
Skeletal muscle glycogen
phosphorylase deficiency
Leads to painful muscle
cramps and exercise
intolerance and fatigue
Myoglobinuria with
strenuous exercise
Impaired ATP production in
muscles due to failure of
muscle glycogen breakdown
Second wind phenomenon
due to increased muscular
blood flow after few minutes
of exercise
Arrhythmia from
electrolyte disturbance
Blood glucose is normal
and liver is normal
Hallmark is low venous
lactate level after exercise
with normal rise in ammonia
levels
 Mutation GNAS gene
McCune- Defect in G protein c-AMP
Albright kinase function in affected
tissue leads to hormone
overproduction
Lethal if mutation occurs
before fertilization but
survivable in patients with
mosaicism
3Ps:
-Precocious puberty
-Polyostotic fibrous dysplasia
-Pigmentation: Large
irregular café au lait spots
Complications:
1-Thyrotoxicosis
2-Cushing syndrome
3-Acromegaly
Triad of :
Meigs -Ovarian fibroma
 -Ascites
syndrome -Pleural effusion
Effusion is not malignant “
no cancer cells in fluid”
Usually resolves after
tumor removal
Mitochondrial encephalo-
MELAS myopathy, lactic acidosis and
syndrome stroke like episodes
2ry to failure of oxidative
phosphorylation in
mitochondria
Muscle biopsy >> ragged
red fibers due to
accumulation of diseased
mitochondria in the
subsarcolemma of the
muscle fiber
Autosomal dominant
MEN 1 Parathyroid cancer
 Pancreatic cancer/
(previously Gastrinoma
known as Pituitary adenoma
Wermer
syndrome)
Gain of function mutation
MEN 2A in RET oncogene on
chromosome 10
Parathyroid cancer
Medullary thyroid cancer
Pheochromocytoma

Gain of function mutation

MEN 2B in RET oncogene on
chromosome 10
Pheochormocytoma
Medullary thyroid
carcinoma
Marfanoid habitus/mucosal
neuroma
 X-linked recessive disorder
Menkes due to mutation in ATP7A
disease gene, leads to defective
Menkes protein >> impaired
copper absorption and
transport
↓ activity of lysyl oxidase
leads to defective collagen
cross linking
Symptoms:
1. Brittle kinky hair
2. Osteoporosis
3. Growth retardation
4. Hypotonia, seizures
5. ↓body temperature
Usually fatal in childhood
A rare mitochondrial
MERRF myopathy
syndrome Stands for : myoclonic
epilepsy with ragged red
fibers
 Lysosomal storage disease,
Meta- AR
chromatic Deficiency in arylsulfatase A
leuko-
enzyme leads to
dystrophy
accumulation of sulfatides
Defective myelin synthesis
Central and peripheral
demyelination
Hypotonia
Hyporeflexia
Ataxia
Dementia

Munchause
n
Lysosomal storage disease ,
Neimann- AR
Pick Deficiency of
sphingomyelinase enzyme
leads to accumulation of
sphingomyelin
Cheery red spot on macula
HSM present
Progressive neuro-
degeneration
Foam cells >> lipid laden
macrophages
 Removal of cortisol
Nelson feedback mechanism after
syndrome bilateral adrenalectomy for
refractory Cushing disease
Lead to enlargement of
existing ACTH-secreting
pituitary adenoma
Presents with:
1)hyper pigmentation
2)headaches 3)bitemporal
hemianopia
Autosomal dominant
Neurofibro disorder caused by
matosis mutations in NF-1 tumor
type 1
suppressor gene located on
chromosome 17
Café au lait spots
Cutaneous neurofibromas
Axillary/inguinal freckling
Optic gliomas
Iris hamartomas (Lisch
nodules)
Long bone dysplasia and
pseudoarthrosis (typically
present in toddlers)
Other associated tumors
include: meningioma,
astrocytoma, glioma and
pheo-chromocytoma
 Bilateral acoustic neuromas
Neurofibro Brain meningiomas,
matosis ependymomas
type 2
Dorsal root schwannomas
Juvenile cataracts
Hearing loss and balance
disturbances from cranial
nerve VIII affection
Acute colonic pseudo-
Ogilvie obstruction
syndrome
Left recurrent laryngeal
Ortner neurapraxia due to
syndrome impingement by dilated left
atrium
Present by hoarseness of
voice due to paresis of vocal
cord muscles
Hereditary hemorrhagic
Osler- telangiectasia
 Autosomal dominant
Weber- Affects skin and mucous
Rendu membranes
syndrome
Common sites: lips,
oronasopharynx, respiratory
tract, GIT, urinary tract
Rare sites: brain, liver,
spleen
Rupture will cause
epistaxis, GI bleeding and
hematuria

Parinaud
Trisomy 13
Patau Cutis aplasia
syndrome
Microphthalmia
Polydactyly
Cardiac abnormalities
Holoprosencephaly
Midline defects:
-Omphalocele
-Cleft lip/palate
-Umbilical hernia
 GIT polyposis
Peutz- Mucocutaneous
Jeghers pigmentation (Lips & oral
mucosa melanosis)
Increased risk of cancers
Estrogen secreting tumor
>> precocious puberty
1st pharyngeal arch defect
Pierre Hypoplasia of the mandible
Robin leads to a “sequence” of
sequence
events
Micrognathia
Glossoptosis
Cleft palate U-shaped
Airway obstruction

Glycogen storage disease

Pompe’s type II
Lysosomal α-1-4
glucosidase deficiency with
α-1-6 glucosidase activity
Cardiomegaly
Hypotonia
Exercise intolerance
Hepatomegaly (usually
related to heart disease and
not from glycogen storage)
Everything is intact except
lysosomes where glycogen
accumulate and cause
disease
 Oligohydramnios leads to a
Potter sequence of events >
sequence 1. Flat facies
2. Pulmonary hypoplasia
3. Limb defects
4. Renal failure in utero
 Causes include: ARPKD,
bilateral renal agenesis,
posterior urethral valve and
chronic placental
insufficiency.
Absent paternal 15q11-q13
Prader- Obese short hypotonic
Willi child
Delayed milestones
Poor suckling in newborn
Hypogonadism and delayed
puberty
Hyperphagia
Intellectual disability
Almond shaped eyes
 
Prune belly
Facial nerve palsy due to
Ramsay herpes zoster infection
Hunt
syndrome
Autosomal recessive
Refsum disorder of α-oxidation
disease Phytanic acid is not
metabolized to pristanic acid
leads to phytanic acid
accumulation
Symptoms:
1. Scaly skin
2. Cataracts/night blindess
3. Ataxia
4. Shortening of the 4th toe
5. Epiphyseal dysplasia
Treatment: diet and
plasmapheresis
 
Reye

Romano-
Ward
Direct hyperbilirubinemia
Rotor’s Normal AST,ALT,ALP
syndrome
Syndrome of Apparent
SAME Mineralocorticoid Excess
syndrome Occur due to deficiency in
11β-HSD enzyme which
normally inactivates excess
cortisol into cortisone
Normally cortisol can bind
to mineralocorticoid
receptors and in this case
the excess cortisol leads to
excessive mineralocorticoid
receptor activity
Leads to :
-Metabolic alkalosis
-Hypokalemia
-Hypertension
-↓ aldosterone
Autosomal recessive
disease
Can be acquired through
consumption of licorice
which contains glycyrrhetinic
acid that blocks the activity
of 11β-HSD
Treatment:
-K sparing diuretics (anti-
mineralocorticoid effect)
-Exogenous corticosteroid to
decrease endogenous
cortisol production and
activity on the receptors
 Presents in infants
Sandifer Arching of the back during
or after feeding
Spasmodic torticollis
Associated with GERD and
Esophagitis

Sjogren’s
Cutaneous angiosarcoma
Stewart- that develops in people with
Treves longstanding lymphedema
Syndrome
Most patients have history
of breast cancer that was
treated with radical
mastectomy
Encephalo-trigeminal
Sturge- angiomatosis
Weber Leptomeningeal angiomas
Mental
retardation/seizures
Visual impairment
Port-wine stain over
trigeminal area (cutaneous
facial angioma)
Hemiplegia
Skull radiopacities
Skull x-ray show “tram-
track” calcifications
 Gonadal dysgensis
Swyer No ovaries or testes
develop in utero
As a result mullerian
organs develop into female
internal geneitalia regardless
of the chromosomal sex due
to lack of MIF
Absence of testosterone
leads to external female
genitalia
No puberty occurs due to
lack of estrogen production
(no breast development , no
menstruation)
Lysosomal storage disease,
Tay-Sachs AR
Deficiency of
hexosaminidase A enzyme
leads to accumulation of
GM2 ganglioside
Cherry red spot on macula
No HSM
Progressive neuro-
degeneration
Hyper reflexia
Hyper acusis > startles
easily
Lysosomes with onion skin
appearance
 Inherited mutation in THRβ
Thyroid gene responsible for thyroid
hormone hormone receptor beta
resistance
expression
syndrome
Leads to resistance to
thyroid hormone and
pituitary perception of low
thyroid levels >> ↑TSH, T3 &
T4 levels.
Thyroid hormone receptor
α -abundantly present in CNS
and heart- function is
preserved, leading to ADHD
and tachycardia
Autosomal dominant
Treacher Failure of neural crest cells
Collins migration to 1st pharyngeal
syndrome
arch
Micrognathia
Mandibular and zygomatic
hypoplasia
Small or absent ears >>
deafness
Glossoptosis (tongue
retraction)
Airway compromise
 Migratory superficial
Trousseau thrombophlebitis
syndrome Associated with visceral
adenocarcinoma due to
hypercoagulable state
Autosomal dominant
Tuberous mutation in tuberin and
sclerosis hamartin
Cysts in kidney, liver &
pancreas
CNS: cortical and
subendymal hamartomas
Cutaneous angiofibromas
(adenoma sebaceum)
Visceral cysts
Renal angiomyolipoma
Cardiac rhabdomyoma
45,XO commonly due to
Turner’s loss of paternal copy of X
chromosome
Widely spaced
nipples/broad chest
Webbed neck (congenital
lymphedema)
Short stature
Low hairline
Cubitus valgus
Streak gonads
Bicuspid aortic valve
Coarctation of the aorta
Horseshoe kidney
Cystic hygroma
 Vertebral
VACTERL Anal atresia
Cardiac
Trachea-Esophageal fistula
Renal
Limb defects
Neurofibromatosis type 1
Von Café au lait spots
Recklingha
Neurofibromas
usen
Optic nerve gliomas
Lisch nodules in iris
Glycogen storage disease
Von- type I
Gierke’s Glucose-6-phosphatase
deficiency
Impaired gluconeogenesis
and glycogenolysis
Hepatomegaly
Renomegaly
Fasting hypoglycemia
Increased blood lactate,
uric acid (gout) and TGs
Muscles are not involved
 Autosomal dominant
Von-Hippel- disease
Lindau Caused by deletion,
nonsense or frameshift
mutations in the VHL gene
on chromosome 3p
Somatic mutation of the
gene causes sporadic RCCs
present as single tumors,
germline mutation is
responsible for the
syndrome with multiple
tumors
Hemangioblastomas in
retina &/or cerebellum
Clear cell RCC
Pheochromocytoma
Lateral medullary
Wallenberg syndrome
syndrome Caused by PICA strokes
Affects: nucleus ambiguous,
vestibular nuclei, spinal
trigeminal nucleus, lateral
spinothalamic tract,
sympathetic fibers and
inferior cerebellar peduncle
 Acute primary adrenal
Waterhouse insufficiency due to adrenal
Friderichse hemorrhage
n
Associated with
meningococcemia , DIC,
endotoxic shock

Weber’s
syndrome
Spinal muscular atrophy
Werdnig- type 1
Hoffmann Caused by autosomal
disease
recessive mutation in SMN1
gene
Congenital degeneration of
anterior horn cells >> LMN
lesions
Floppy baby
Flaccid paralysis
Tongue fasciculation
 Symmetric weakness
 Classic triad of confusion,
Wernicke- ophthalmoplegia and ataxia
Korsakoff Occurs in alcoholics due to
thiamine deficiency
May be predisposed by
abnormal transketolase
enzyme
Other symptoms include:
confabulation, memory loss,
personality changes and
nystagmus
Damage to medial dorsal
nucleus of thalamus and
mammillary bodies occur
Elfin facies
William’s Supravalvular aortic
stenosis
Extroverted personality
Immuno-deficiency
Wiskott- Eczema
 Thrombocytopenia
Aldrich

Wolff-
Parkinson_
white
Autosomal recessive
Zellweger disorder caused by PEX
syndrome genes mutation
Impaired metabolism of
VLCFAs
Accumulation in tissues
lead to neurologic defects
due to impaired neuronal
migration, myelination and
degeneration
Presents in early infancy
with craniofacial
abnormalities (wide sutures,
large anterior fontanelle)
Hepatomegaly
Hypotonia
Seizures
Developmental delay
Death within months of
presentation
 Gastrin producing tumor
Zollinger- Multiple refractory ulcers
Ellison (Duodenal and Jejunal)
Dx >> serum gastrin >1000
pg/mL in the presence of
normal PH gastric acid (<4)
Positive secretin
stimulation test: gastrin
levels remain high after
secretin administration
(normally secretin inhibits
gastrin release)
Could be part of MEN 1
Diarrhea/ Steatorrhea are
usually present
Malabsorption