Genetic Disorders - Sheet1 (1) Flashcards
(64 cards)
1
Q
- Severe photosensitivity
- Hyperpigmentation in sun-exposed areas
- Increased risk for skin cancer
Etiology? Inheritance?
A
Xeroderma Pigmentosum
Defective Nucleotide Excision Repair
Autosomal recessive
2
Q
- Colorectal cancer
- Endometrial cancer
- Ovarian cancer
- Skin cancers
Etiology? Inheritance?
A
Lynch Syndrome (HNPCC)
Defective Mismatch Repair (MLH1)
Autosomal dominant
3
Q
- Immnodeficiency
- Gait instability & ataxia
- Cutaneous telangiectasias
Etiology?
A
Ataxia Telangiectasia
Defective repair of double-stranded DNA breaks
(ATM gene)
4
Q
- Genetic susceptibility to
- breast
- ovarian
- pancreatic cancers
Etiology?
A
BRCA1 Mutation
Defective repair of double-stranded DNA breaks
5
Q
- Young child with pancytopenia
- Dry bone marrow tap
- Short stature
- Absent thumb/radial defects
- Cafe-au-lait spots
- Increased risk for leukemia/tumors
Etiology?
A
Fanconi anemia
Defective repair of double-stranded DNA breaks
6
Q
- Rapid onset macrocytic anemia within 1st year of life
- Short stature
- Craniofacial abnormalities
- Triphalangeal thumbs
A
Diamond Backfan Anemia
7
Q
- Multiple fractures with minimal trauma
- Blue sclerae
- Dental abnormalities
- Hearing loss
Etiology? Inheritance?
A
Osteogenesis Imperfecta
Defective type I collagen
Autosomal dominant
8
Q
- Hyperextensible skin
- Easy bruising
- Hypermobile joints & joint dislocation
Etiology?
A
Ehlers-Danlos Syndrome (Classical type)
Defect in type V collagen
9
Q
- Many berry aneurysms
- Risk for aortic aneurysms
- Organ rupture
Etiology?
A
Ehlers-Danlos Syndrome (Vascular type)
Defect in type III collagen
10
Q
- Brittle, kinky hair
- Growth retardation
- Hypotonia
Etiology? Inheritance?
A
Menkes Disease
Impaired copper absorption
(ATP7A mutation) leads to decreased lysyl oxidase activity (collagen cross-linking)
X-linked recessive
11
Q
- Tall with long extremities & arachnodactyly
- Pectus carinatum/excavatum
- Hypermobile joints
- Medial necrosis of aorta (risk for aneurysms)
- Aortic regurgitation
- Floppy mitral valve
- Subluxation of lens
Etiology? Inheritance?
A
Marfan Syndrome
Defective fibrillin (FBN1 gene)
Autosomal dominant
12
Q
- Fibrous dysplasia of several bones
- Precocious puberty
- Unilateral hyperpigmented cutaneous macules with ragged edges
- Other endocrinopathies
Etiology?
A
McCune-Albright Syndrome
Activating mutation in G-protein signaling (exhibits mosaicism)
13
Q
- Hyperphagia
- Obesity
- Intellectual disability
- Hypogonadism
- Hypotonia
Etiology?
A
Prader-Willi Syndrome
Paternal mutation, maternal imprinting
14
Q
- Inappropriate laughter
- Seizures
- Ataxia
- Severe intellectual disability
Etiology?
A
Angelman Syndrome
Maternal mutation, paternal imprinting
15
Q
- Child with bowed legs & soft bones
- Resistant to vitamin D supplementation
Etiology? Inheritance?
A
Hypophosphatemic rickets
Phosphate wasting at proximal tubule
X-linked dominant
16
Q
- Autism & intellectual disability
- Long face with large jaw
- Large everted ears
- Macroorchidism
- Mitral valve prolapse
Etiology? Inheritance?
A
Fragile X Syndrome
CGG repeat expansion in FMR1 gene (hypermethylation)
X-linked dominant
17
Q
- Retinopathy & lens dislocation
- Sensorineural deafness
- Glomerulonephritis
Etiology? Inheritance?
A
Alport Syndrome
Defect in type IV collagen
X-linked dominant
18
Q
- Recurrent pulmonary infections
- Chronic bronchitis & bronchiectasis
- Malabsorption with steatorrhea
- Biliary cirrhosis & liver disease
- Meconium ileus in newborns
- Infertility in men, subfertility in women
- Nasal polyps
- Clubbing of nails
Etiology? Inheritance?
A
Cystic fibrosis
CFTR Phe508 deletion
Autosomal recessive
19
Q
- Adolescent onset of proximal muscle weakness
- Calf pseudohypertrophy
- Positive Gower sign
Etiology? Inheritance?
A
Becker Muscular Dystrophy
Mutation in dystrophin gene (not frameshift)
X-linked recessive
20
Q
- Early onset proximal muscle weakness
- Calf pseudohyertrophy
- Positive Gower sign
- Dilated cardiomyopathy
Etiology? Inheritance?
A
Duchenne Muscular Dystrophy
Frameshift mutation in dystrophin gene
X-linked recessive
21
Q
- Delayed muscle relaxation after contraction
- Muscle wasting
- Cataracts
- Testicular atrophy
- Frontal balding (toupee)
- Arrhythmias
Etiology? Inheritance?
A
Myotonic dystrophy
CTG repeat expansion in DMPK gene
Autosomal dominant
22
Q
- Sudden, jerky movements of limbs
- Snake-like writhing of fingers
- Agression
- Depression
- Dementia
Etiology? Inheritance?
A
Huntington Disease
CAG repeat expansion (deacetylation)
Autosomal dominant
23
Q
- Muscle weakness
- Loss of deep tendon reflexes, vibratory sense, proprioception
- Staggering gait with frequent falls
- Nystagmus
- Dysarthria
- Pes cavus
- Hammer toes
- Diabetes mellitus
- Hypertrophic cardiomyopathy
- Kyphoscoliosis
Etiology? Inheritance?
A
Friedreich Ataxia
GAA repeat expansion frataxin gene
Autosomal recessive
24
Q
- Intellectual disability
- Flat facies
- Prominent epicanthal folds
- Single palmar crease
- Gap between 1st & 2nd toes
- Duodenal atresia
- Hirschsprung disease
- Atrioventricular septal defect
- Brushfield spots in eyes
- Early onset Alzheimer disease
- Increased risk of ALL & AML
Etiology?
A
Down syndrome
Trisomy 21
25
* Intellectual disability
* Prominent occiput
* Rocker-bottom feet
* Clenched fists with overlapping fingers
* Low-set ears
* Micrognathia
* Congenital heart disease
* Death usually by age 1
Etiology?
Edwards Syndrome
Trisomy 18
26
* Intellectual disability
* Rocker-bottom feet
* Microphthalmia
* Microcephaly
* Cleft lip/palate
* Holoprosencephaly
* Polydactyly
* Cutis aplasia
* Congenital heart disease
* Death usually by age 1
Etiology?
Patau Syndrome
Trisomy 13
27
* Microcephaly
* Epicanthal folds
* Intellectual disability
* High pitched crying/meowing
* Cardiac VSD
Etiology?
Cri-du-chat Syndrome
Microdeletion of chromosome 5 short arm
28
* Intellectual disability
* Hypercalcemia
* Well-developed verbal skills
* Extreme friendliness with strangers
* Distinctive elfin facies
* Cardiovascular problems
Etiology?
Williams Syndrome
Microdeletion of chromosome 7
29
* Thymic aplasia & immunodeficiency
* Hypocalcemia
* Cardiac defects
* Facial & palatal abnormalities
Etiology?
DiGeorge Syndrome
22q11 deletion (impaired development of 3rd & 4th branchial pouches)
30
* Cleft palate
* Abnormal facies
* Cardiac defects
Etiology?
Velocardiofacial Syndrome
22q11 deletion (impaired development of 3rd & 4th branchial pouches)
31
* Port-wine stain of face
* Ipsilateral leptomeingeal angioma
* Seizures & epilepsy
* Intellectual disability
* Episcleral hemangioma
* Early-onset glaucoma
Etiology?
Sturge-Weber Syndrome (Encephalotrigeminal angiomatosis)
Abnormal development of neural crest derviatives
(GNAQ gene mutation)
32
* Hamartomas in CNS & skin
* Angiofibromas
* Mitral regurgitation
* Ash-leaf spots
* Cardiac rhabdomyomas
* Intellectual disability
* Renal angiomyolipoma
* Seizures Shagreen patches
* Subependymal giant cell astrocytomas
* Ungual fibromas
Etiology? Inheritance?
Tuberous sclerosis
TSC1/2 mutation
Autosomal dominant
33
* Hyperpigmented cutaneous macules with smooth edges
* Cutaneous neurofibromas
* Optic gliomas
* Pheochromocytomas
* Lisch nodules (pigmented iris hamartomas)
Etiology? Inheritance?
Neurofibromatosis type I (von Recklinghausen disease)
NF1 tumor suppressor mutation
Autosomal dominant
34
* Bilateral acoustic schwannomas
* Juvenile cataracts
* Meningiomas
* Ependymomas
Etiology? Inheritance?
Neurofibromastosis type II
NF2 tumor suppressor mutation
Autosomal dominant
35
* Hemangioblastomas in retina, brain stem, cerebellum, & spine
* Angiomatosis (skin, mucosa, organs)
* Renal cell carcinomas
* Pheochromocytomas
Etiology? Inheritance?
Von Hippel-Lindau Disease
VHL gene deletion
Autosomal dominant
36
* Hemolytic anemia in response to
* infection
* fava beans
* sulfonamides
* primaquine
* anti-TB drugs
Etiology? Inheritance?
G6PD Deficiency
Defect in glucose-6-phosphate dehydrogenase
X-linked recessive
37
* Normocytic anemia
* Increased reticulocyte counts
* Splenomegaly
* Normal haptoglobin
* Spherocytes on blood smear
* Frequent gallstones
Etiology? Inheritance?
Hereditary Spherocytosis
Ankyrin/band3/spectrin defect
Autosomal dominant
38
* Pituitary tumor
* Pancreatic endocrine tumor
* Parathyroid hyperplasia
Etiology? Inheritance?
MEN 1 Syndrome
MEN1 gene mutation (menin)
Autosomal dominant
39
* Parathyroid hyperplasia
* Pheochromocytoma
* Medullary thyroid carcinoma
Etiology? Inheritance?
MEN 2A Syndrome
RET gene mutation
Autosomal dominant
40
* Pheochromocytoma
* Medullary thyroid carcinoma
* Mucosal neuromas
* Marfanoid habitus
Etiology? Inheritance?
MEN 2B Syndrome
RET gene mutation
Autosomal dominant
41
* Thousands of colonic polyps starting after puberty
Etiology? Inheritance?
Familial adenomatous polyposis (FAP)
APC gene mutation
Autosomal dominant
42
* Thousands of colonic polyps starting after puberty
* Osseous & soft tissue tumors
* Congenital hypertrophy of retinal pigment epithelium
* Impacted, supernumerary teeth
Gardner Syndrome
43
* Thousands of colonic polyps
* Medulloblastomas
* Gliomas
Turcot Syndrome
44
* Hamartomas in GI tract
* Hyperpigmented mouth, lips, hands, & genitalia
* Increased risk of:
* breast cancers
* colorectal cancers
* stomach cancers
* small bowel cancers
* pancreatic cancers
Inheritance?
Peutz-Jeghers Syndrome
Autosomal dominant
45
* Children (\< 5yrs old) with hamartomatous polyps in colon, stomach, & small bowel
* Increased risk of colorectal cancer
Inheritance?
Juvenile polyposis syndrome
Autosomal dominant
46
* Mild jaundice that occurs with stress, illness, or fasting
* Increased unconjugated bilirubin
* No hemolysis
Etiology? Inheritance?
Gilbert Syndrome
Decreased UDP-glucuronosyltransferase
Autosomal Recessive
47
* Jaundice
* Kernicerus
* Increased unconjugated bilirubin
* No hemolysis
Etiology? Inheritance?
Crigler-Najjar Syndrome
Absent UDP-glucuronosyltransferase
Autosomal Recessive
48
* Black liver
* Elevated conjugated bilirubin
* No biliary tract obstruction
Etiology? Inheritance?
Dubin-Johnson Syndrome
Defective liver excretion of bilirubin
Autosomal Recessive
49
* Elevated conjugated bilirubin
* No biliary tract obstruction
* Liver is not black
Etiology? Inheritance?
Rotor Syndrome
Defective liver excretion of bilirubin
Autosomal Recessive
50
* Liver disease
* Dysarthria, dystonia
* Tremor, parkinsonism
* Psychiatric disease
* Kayser-Fleischer rings in cornea
* Hemolytic anemia
* Fanconi Syndrome
* Decreased serum ceruloplasmin
Etiology? Inheritance?
Wilson Disease
ATP7B gene mutation
Autosomal Recessive
51
* Cirrhosis
* Diabetes mellitus
* Skin hyperpigmentation
* Cardiomyopathy
* Hypogonadism
* Arthropathy (pseudogout)
Etiology? Inheritance?
Hemochromatosis
HFE gene mutation (C282Y)
Autosomal Recessive
52
* Respiratory distress
* Right heart failure
* Atherosclerosis, fibrosis, & plexiform lesions in pulmonary artery
Etiology?
Heritable Pulmonary Arterial Hypertension
Mutation in BMPR2 gene/ endothelin
53
* Hypokalemia
* Metabolic alkalosis
* Hypercalciuria
* Increased plasma renin & aldosterone
Etiology? Inheritance?
Bartter Syndrome
Defect in NKCC transporter in ascending limb of loop of Henle
Autosomal Recessive
54
* Hypokalemia
* Metabolic alkalosis
* Hypocalciuria
* Hypomagnesemia
* Increased plasma renin & aldosterone
Etiology? Inheritance?
Gitelman Syndrome
Defect in NaCl transporter in DCT
Autosomal Recessive
55
* HTN
* Hypokalemia
* Metabolic alkalosis
* Decreased renin & aldosterone
* Normal levels of cortisone
Etiology? Inheritance?
Liddle Syndrome
Activation of ENaC
Autosomal Dominant
56
* Wilms tumor
* Aniridia
* Genitourinary malformations
* Mental retardation
Etiology?
WAGR complex
WT1 deletion
57
* Wilms tumor
* Early-onset nephrotic syndrome
* Male pseudohermaphroditism
Etiology?
Denys-Drash
WT1 mutation
58
* Wilms tumor
* Macroglossia
* Organomegaly
* Hemihyperplasia
Etiology?
Beckwith-Wiedemann
WT2 mutation
59
* Cysts & abnormal connective tissue in the kidney at birth
* Can be unilateral or bilateral
Etiology?
Multicystic Dysplastic Kidney
Congenital malformation (non-inherited)
60
* HTN with increased renin
* Hematuria
* Enlarged kidneys with cysts in cortex & medulla
* Berry aneurysms
* Hepatic cysts
* Mitral valve prolapse
Etiology? Inheritance?
Autosomal Dominant PKD
APKD1 or APKD2 gene mutation
61
* Renal failure & HTN in infant
* Enlarged kidneys with cysts in cortex & medulla
* Potter sequence
* Hepatic fibrosis & cysts
Inheritance?
Autosomal Recessive PKD
62
* Shrunken kidneys & renal failure
* Cysts in medullary collecting ducts
Inheritance?
Medullary cystic kidney disease
Autosomal dominant
63
* Recurrent epistaxis
* Easy bruising
* Petechiae & purpura
* Increased bleeding time
* Increased PTT, normal PT
* No aggregation with ristocetin assay
Etiology? Inheritance?
Von Willebrand Disease
vWF deficiency
Autosomal dominant
64
* DVT at early age
* Cerebral vein thromboses
* Recurrent pregnancy loss
Etiology?
Factor V Leiden
Mutant factor V resistant to degradation
