π¨βπ©βπ§βπ¦ Genetics D/O Flashcards
Trisomy 21
DOWN SYNDROME
Most common chromosomal disorder and cause of congenital mental retardation
DOWN SYNDROME
95% due to MEIOTIC NONDISJUNCTION of homologous chromosomes
DOWN SYNDROME
Advanced maternal age (>45.y.o.) (35-40)
DOWN SYNDROME
Most common preventable congenital mental retardation
CREETINISM
Mongoloid facies features (flat faced, low bridged nose and epicanthal folds)
DOWN SYNDROME
Brushfield spots-speckled appearance of the iris
Muscular hypotonia
DOWN SYNDROME
Simian crease or palmar crease
DOWN SYNDROME
Alzheimerβs disease in >35 years old (in adults)
DOWN SYNDROME
Most common malformation of DOWN SYNDROME
ENDOCARDIAL CUSHION DEFECT
Increase risk of ACUTE LYMPHOBLASTIC LEUKEMIA (in children)
DOWN SYNDROME
Most common ASD in DOWN SYNDROME in adults
Ostium primum
Most common ASD in DOWN SYNDROME IN CHILDREN
Ostium secundum
Antenatal
AFP value of approximately 0.7 MoM
HCG level of approximately 2.0 MoM
Unconjugated estriol concentration of approximately 0.8 MoM
TRIPLE TEST
A fourth marker, dimeric inhibin alpha was added values of about 1.8 MoM are reported in DOWN SYNDROME
QUAD TEST
Neurofibrillary tangle (NFT)
Amyloid plaques
- both composed of protein TAU
Alzheimers Disease
Trisomy 18
EDWARDS SYNDROME
Severe MR
Rocker bottome feet
Low set ears
Micrognathia
CHD
Clenched hands (flexion of fingers) Overlapping flexed fingers
Prominent occiput
Death within 1 year
EDWARDS SYNDROME
47XX or XY+18
EDWARDS SYNDROME
Second most common autosomal trisomy after trisomy 21
EDWARDS SYNDROME
Trisomy 13
PATAU SYNDROME
47XX or XY+13
PATAU SYNDROME
Trisomy 13
PATAU SYNDROME
MULTIPLE CONGENITAL ANOMALIES
Severe MR
Microphthalmia
Microcephaly
Cleft palate/lip
Polydactyly
Congenital heart disease
Death occurs within 1 year of birth
PATAU SYNDROME
Taken with misoprostol
PATAU SYNDROME
Cholesterol transport across liver cell impaired
FAMILIAL HYPERCHOLESTEROLEMIA
HDL receptor defect
TANGIERS DISEASE
47XX or XY+21
DOWN SYDNROME
LDL receptor defect
FAMILIAL HYPERCHOLESTEROLEMIA
Deficiency of a-galactosidase A
FABRYβs DISEASE
Deficiency of b-glucocerebrosidase
GAUCHERS DISEASE
Deficiency of sphingomyelinase
NIEMANN-PICK DISEASE
Absent HEXOSAMINIDASE A deficiency
TAY-SACHβ S DISEASE
Deficiency of alpha-L iduronidase
HURLERβs DISEASE
Deficiency of iduronate-2-sulfatase
HUNTERβs DISEASE
Erlemeyer flask appearance
GAUCHERS DISEASE
Crumpled paper or tissue appearance
GAUCHERS DISEASE
Deficiency of HEXOSAMINIDASE A and B
SANDHOFF DISEASE
Fibrillin-1 defect
MARFAN SYNDROME
D/O causing ICTOPIA LENTIS
MARFAN SYNDROME and HOMOCYSTINURIA
Sublaxation of lenses
ICTOPIA LENSES
Classical hypermobility
EHLERS DANLOS SYNDROME
Defective collagen (type 1,3 and 5)
EHLERS DANLOS SYNDROME
What collagen is OSTEOGENESIS IMPERFECTA
Type 1
Skeletal features:
- most striking feature
- unusually tall with long, thin extremities (dolichostenomelia)
- long tapering fingers and toes with spider-like appearance (arachnodactyly)
MARFANS SYNDROME
Cardiovascular features:
- most life threatening feature
- 2 common lesions: mitral valve prolapse, dilation of the ascending medionecrosis
MARFANS SYNDROME
First one to be described HOMOGENTISIC ACID
ALCAPTONURIA
HOMOGENTISIC ACID OXIDASE deficiency
ALCAPTONURIA
Pigmentation of sclera
OSLERS SIGN
Note: OSLERβS NODE - Infective Endocarditis
Black urine
Black nails (OCHRONOSIS)
Black skin
Black joint cartilage (severe arthritis)
ALCAPTONURIA
Happy puppet syndrome
ANGELMAN SYNDROME
Chromosome 15
ANGELMAN SYNDROME and PRADER-WILLI SYNDROME
Chromosome 17
VON RECKLINGHAUSEN
Obesity, small stature, hyperphagia and mental retardation
Deletion of chromosome 15
PRADER WILLI SYNDROME
Hereditary motor and sensory neuropathy (HMSN)
CHARCOT MARIE TOOTH DISEASE
Peroneal muscular atrophy (PMA)
CHARCOT MARIE TOOTH DISEASE
Most common peripheral neuropathy worldwide
CHARCOT MARIE TOOTH DISEASE
70-80% is the duplication of a large regiom on the short arm of chromosome 17 that includes the gene PMP22
CHARCOT MARIE TOOTH DISEASE
Foot drop
High arched foot
Stork legs
Hammer toes
CHARCOT MARIE TOOTH DISEASE
Ataxia, nystagmus, kyphoscoliosis and pes cavus
Chromosome 9
FRIEDREICH ATAXIA
Frataxin gene
FRIEDREICH ATAXIA
46XX or XY,5pb
CRI DU CHAT SYNDROME
Deletion of the short arm of chromosomes
CRI DU CHAT SYNDROME
High pitched cat-like cry
Mental retardation
Congenital heart disease
Microcephaly
CRI DU CHAT SYNDROME
Due to dynein arm defect
KARTAGENERβS SYNDROME
Hepatolenticular degeneration due to decreases levels of CERULOPLASMIN
WILSONβs DISEASE
Copper accumulation (CERUPLASMIN)
WILSONβs disease and MENKES DISEASE
Kayser-Fleischer Rings
WILSONβS DISEASE
Causes CHOREA or involuntary movements
Rheumatic fever
Huntingtons disease
Wilsons disease
Male XXY or 47XXY
KLINEFELTERS SYNDOME
The extra (inactive X chromosome BARR BODY)
KLINEFELTERS SYNDOME
Elevated FSH and LH
low levels of testosterone
BARR BODY
Female XO or 45XO
TURNERβS SYNDROME
Short stature, ovarian dysgenesis, webbed neck, coarctatiom of aorta
Common cause of amenorrhea
TURNERβS SYNDROME
Female hypogonadism
Second X chromosome is necessary for oogenesis and normal development of ovary
No BARR BODY present
TURNERβS SYNDROME
Most common sex chromosome and abnormality in females
TURNERβS SYNDROME
Male hypogonadism
KLINEFELTERβS SYNDROME
Cafe au lait spots
VON RECKLINGHAUSEN and McCUNE ALBRIGHT
Bilateral tinnitus and deafness
ACOUSTIC SCHWANOMA
CANT SEE -UVEITIS
CANT PEE - URETHRITIS
CANT CLIMB A TREE - ARTHRITIS
REITERβS SYNDROME
Seronegative spondyloarthropathy
HLA-B27
REITERβS SYDNROME
Both causing uveitis
REITERβS SYDROME and BEHCET DISEASE
Monogenetic disorder
Average life span: 28 yrs old
Chronic airway infection
CYSTIC FIBROSIS
Colon becomes covered with adenomatous polyps after puberty
FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
Testicular atrophy
Infertility due to azoospermia
Eunuchoid body habitus
High-pitched voice
Female distribution of hair
Gynecomastia
KLINEFELTERβS SYNDROME
Failure to develop secondary sex characteristics
Short stature bilateral
Atrophic βsteakedβ ovaries
Primary amenorrhea
Infertility
TURNERS SYNDROME
Clinical manifestations at birth:
Congenital lymph edema
Redundant skin folds
Webbing of the neck
TURNERS SYNDROME
Broad chest and widely spaced nipples
Cubitus valgus (outward)
Pigmented nevi
Constriction of aorta (coarctation of the aorta)
TURNERS SYNDROME
Chromosome 5
FAMILIAL ADENOMATOUS POLYPOSIS
Chromosome 7
CYSTIC FIBROSIS
Absence of HGPRTase
LESCH-NYLAN SYNDROME
Lacks NUCLEOTIDE SALVAGE (purine)
LESCH-NYLAN SYNDROME
Autosomal dominant
HUNTINGTON DS
NEUROFIBROMATOSIS
MYOTONIC DYSTROPHY
TUBEROUS SCLEROSIS
POLYCYSTIC KIDNEY
HEREDITARY SPHEROCYTOSIS
VON WILLEBRAND DS
MARFAN SYNDROME
EHLERS DANLOS
OSTEOGENESIS IMPERFECTA
ACHONDROPLASIA
FAMILIAL HYPERCHOLESTEROLEMIA
ACUTE INTERMITTENT PORPHYRIA
Floppy valve syndrome
MARFANS SYNDROME
Cystic medionecrosis
MARFANS SYNDROME
Defects in both humoral and cell mediated immune response
Thrush (oral candidiasis), extensive diaper rash and failure to thrive
Morbiliform rash appears shortly after birth
Death occurs if BM transplant is not done within 1sy year of life
SCID
Most common form 50-60% X Linked with a mutation in the common y-chain (yc) subunit of cytokine receptors
SCID
Autosomal recessive
Deficiency of enzyme adenosine deaminase (ADA) - accumulation of deoxyadenosine
SCID
Small thymus devoid of lymphocytes
SCID
Most frequent SCID phenotype
40-50%
Absence of both T and NK cells
X-Linked (cytokine-signaling deficiency)
10-20%
Lymphopenia occurs from the death of T and B cells
ADA deficiency
X-linked recessive
Immunodeficiency with THROMBOCYTOPENIA and ECZEMA
Patients often have prolonged bleeding from the circumcision site or bloody diarrhea durinf infancy
Atopic dermatitis and recurrent infections occur during the 1st year of life
WISKOTT-ALDRICH SYNDROME
Thrombocytopenia, eczema and marked vulnerability to recurrent infections
WISKOTT-ALDRICH SYNDROME
Low IgM
Normal IgG
High IgE and IgA
WISKOTT-ALDRICH SYNDROME
Autosomal recessive
Increased susceptibility to infections owing to defective degranulation of neutrophils
CHEDIAK-HIGASHI SYNDROME
Mild bleeding diathesis, partial oculocutaneous ALBINISM, progressive peripheral neuropathy and a tndency to develop a life threatening lymphoma like syndrome
CHEDIAK-HIGASHI SYNDROME
Group of disorders of granulocyte and monocyte oxidative metabolism
CHRONIC GRANULOMATOUS DISEASE
Inherited as an X-linked recessive trait
30% of patients inherit the disease in an autosomal recessive pattern
CHRONIC GRANULOMATOUS DISEASE
Caused by defective production of reactive oxygen species (ROS) in the phagolysosome membrane following phagocytosis of microorganisms
CHRONIC GRANULOMATOUS DISEASE
Because of a deletion this cannot be detected by standard karyotyping and needs FISH
CHROMOSOME 22q11.2 (DELETION SYNDROME)
X LINKED CONDITIONS
Duchenne muscular dystrophy
Hemophilia A and B
G6PD Deficiency
Agammaglobulinemia
Wiskott-Aldrich Syndrome
Diabetes Insipidus
Lesch-Nylan Syndrome
Fragile-X Syndrome
Monogenetic disorder
Avwrage life span: 28 years old
Chronic airway infection: BRONCHITIS, BRONCHIECTASIS, EXOCRINE PANCREATIC INSUFFICIENCY, INTESTINAL DYSFUNCTION, ABNORMAL SWEAT GLAND FUNCTION, UROGENITAL DYSFUNCTION
CYSTIC FIBROSIS
Enzyme defect which inceases drug susceptibility
G6PD β¬ οΈ PRIMAQUINE
AUTOSOMAL DOMINATN CONDITIONS
Huntingtons disease
Neurofibromatosis
Myotonic dystrophy
Tuberous sclerosis
Polycystic kidney
Hereditary spherocytosis
Von Willebrand disease
Marfan Syndrome
Ehlers-Danlos Syndrome
Osteogenesis Imperfecta
Anchondroplasia
Familial Hypercholemia
Acute Intermittent Porphyria
AUTOSOMAL RECESSIVE
Cystic fibrosis
PKU
Galactosemia
Homocystinuria
Lysosomal storage
A-1 antitrypsin
Wilson disease
Hemochromatosis
Glycogen storage diseases
Hgb S
Thalassemias
Congenital adrenal hyperplasia
Ehlers Danlos
Alkaptonuria
Neurogenic muscle atrophies
Friedreich ataxia
Spinal muscular atrophy
Hepatolenticulqr degeneration due to decreased levels of ceruloplasmin
WILSONS DISEASE
Characterized by ABCD:
ASTERIXIS
BASAL GANGLIA DEGENERATION
CERULOPLASMIN β¬οΈ
Cirrhosis
Corneal deposits
Chorea
Dementia
WILSONS DISEASE
Most common form of childhood muscular dystrophy
DUCHENNE MUSCULAR DYSTROPHY
Dystrophin
DUCHENNE MUSCULAR DYSTROPHY
96% frameshift mutation
30% with new mutation
DUCHENNE MUSCULAR DYSTROPHY
Gowers sign
DUCHENNE MUSCULAR DYSTROPHY
Pseudohypertrophy
DUCHENNE MUSCULAR DYSTROPHY
Bilateral acoustic neuromas
NEUROFIBROMATOSIS TYPE 2
Neurofibromatosis type 1
VON RECKLINGHAUSEN
Cafe au lait spots
Lisch nodules
VON RECKLINGHAUSEN
Milder form of DUCHENNE
BECKERS MUSCULAR DYSTROPHY
Sex linked recessive disorder
Xp21
BECKERS MUSCULAR DTSTROPHY
Partial deletion of the gene coding for dystrophin
BECKERS MUSCULAR DYSTROPHY
Dystrophin is partially present, muscle membrane
Semi functional
Higher chance if susceptibility
BECKERS MUSCULAR DYSTROPHY
Steinertβs Disease
MYOTONIA DYSTROPHICA
PDA
Congenital cataracts
Sensory neural hearing loss
Cardiac problem
CONGENITAL RUBELLA SYNDROME
Carp mouth
Frontal bossing
CTG REPEAT
MYOTONIC DYSTROPHY
Myotonia
Muscle stiffness
Muscle hypertrophy
Herculean appearance
MYOTONIA CONGENITA/THOMSENS DISEASE
Gene mutation encoding chloride channel
Autosomal dominant
MYOTONIA CONGENITA or THOMSENS DISEASE
Ceramide triihexoside
FABRYS DISEASE
Intactable neonatal hypoglycemia
Macroglossia
Omphalocoele
Facial nevus flammeus
Earlobe creases
BECKWITH-WIEDEMANN SYNDROME
Progressive cerebellar ataxia, oculomotor apraxia, choreoathetosis, telangiectasis of the skin and conjuctivae
ATAXIA-TELANGIECTASIA
Cerebellar hemangioblastomas
Multiple congenital cysts kidney
Associated with renal ca
VON HIPPEL LINDAU DISEASE
Self injurious behavior and self mutilation
LESCH NYLAN SYNDROME
Progressive external ophthalmoplegia involving all extra ocular muscles
Pigmentary degeneration of the retina (retinitis pigmentosa)
Bony specule appearance
KEARNS-SAYRE SYNDROME
Most frequent mitochondrial disease of the perinatal period and early infancy
Diffuse encephalopathy
LEIGH ENECEPHALOPATHY (SUBACUTE PERIVENTRICULAR NECROTIZING ENCEPHALOPATHY)
Calcification of the basal ganglia
Present with Parkinsons
FAMILIAL IDIOPATHIC or FAHR DS
Pipecolate oxidase
ZELLWEGER DISEASE or PEROXISOMAL DISORDER or CEREBROHEPATORENAL
Abnormal very long chain fatty acid metabolism
ZELLWEGER
Lipogranulomatosis
FABRY DS
Ceramide deficiency
FABRY DS
Hoarse cry due to fixation of laryngeal cartilage
FARBER DS
Periarticular and subcutaneous swellings and progressive arthropathy
FABRY DS
Marked enlargement of liver
Vacuolated histiocytes βFOAM CELLSβ in the bone marrow
NIEMANN PICK DS
Required to convert phenylalanine to tyrosine
TETRAHYDROBIOPTERIN
Most common cause of genital ambiguity
CONGENITAL ADRENAL HYPERPLASIA