~80 Genetic Disorders Flashcards
Inheritance 1p36.3
Sporadic
3 major clinical features 1p36.3
Neurodev disabilities, characteristic face (straight eyebrows, deep-set eyes), hypotonia
Inheritance Achondroplasia
AD
Gene Achondroplasia
FGFR3
3 major clinical features Achondroplasia
Rhizomelic limb shortening, macrocephaly, trident hands
Characteristic Face Achondroplasia
Frontal bossing, Midface hypoplasia
Inheritance Alagille
AD
5 ‘organ’ systems affected in Alagille
Liver, Heart, Eyes, Skeleton, Face
4 major clinical features Alagille
Bile duct paucity, pulmonic stenosis, posterior embryotoxon, butterfly-shaped vertebrae
Inheritance ALS
Most sporadic (or AD, AR, XL)
3 major clinical features of ALS
Asymmetric limb weakness, bulbar symptoms, muscle atrophy
Inheritance Angelman Syndrome
Imprinted (loss of maternal copy)
Etiologies for Angelman Syndrom
Del mat, pat UPD, loss UBE3A gene
3 major features of Angelman Syndrome
Severe ID with speech problems, ataxia gait, happy/excitable/laughter
Inheritance for Ataxia Telangiectasia
AR
Hallmark in blood of Ataxia Telangiectasia
Elevated AFP
3 major clinical features of A-T
Ataxia (before 5), telangiectasis in eyes and skin, increased risk of leukaemia and lymphoma
Inheritance of Ataxia w/ Oculomotor Apraxia
AR
3 major clinical features of Ataxia with Oculomotor Apraxia
Ataxia, Oculomotor Apraxia, Neuropathy, Chorea
Inheritance of Bardet-Biedl Syndrome
AR
3 major features of Bardet-Biedl Syndrom
Vision problems, obesity, ID, genital anomalies and anosmia
Inheritance of BMD
xlr
3 major clinical features of BMD
Muscle weakness, cardiomyopathy, may live into 40s
Inheritance of BWS
AD (imprinting)
Etiologies for BWS
Imprinting of chromosome 11, paternal UPD of chromosome 11, mutations in CDKN1C
5 clinical features of BWS
Macrosomia, Macroglossia, visceromegaly, hemihyperplasia, abdominal wall defect
Increased risk for what kind of cancer in BWS
Wilm’s Tumor and hepatoblastoma
Inheritance of BOR Syndrome
AD
3 major features of BOR Syndrome
Branchial arch anomalies, ear anomalies with HL, kidney anomalies
Inheritance of CADASIL
AD
3 major features of CADASIL
Migraine with aura, ischemic strokes and TIA, mood/cognitive problems
Inheritance of Canavan Disease
AR
Canavan can be characterized as?
Leukodystrophy
3 major features Canavan
No motor skills, feed/swallowing problems, seizures, sleep problems
Inheritance Cardio-Facial-Cutaneous Syndrome
AD
3 major features of Cardio-Facial-Cutaneous Syndrome
Heart- Pulmonic stenosis, characteristic face, Skin- wirnkled palms/soles
Inheritance of CMT
AD, AR, XL, Mt
3 major features of CMT1A
Toe walking, clumsy, foot deformities
Severity of CMT2A compared to CMT1A
CMT2A is more severe- earlier onset and require wheelchair
Inheritance of CHARGE syndrome
AD
CHARGE stands for what features?
Coloboma, Heart defect, Atresia Choanal, Retarded growth, Genital abnormalities, Ear abnormalities
Inheritance Cleidocranial Dysplasia
AD
3 major features of Cleidocranial dysplasia
Bone- absent clavicles, unusually shaped teeth, dysmorphic face
Inheritance Cockayne Syndrome
AR
3 major features of Cockayne Syndrome
Microcephaly, photosensitivity, FTT
People with Cockyne Syndrome have life threatening allergy to?
Metronidazole (antibiotic)
Inheritance Coffin-Lowry Syndrome
XLD
What sex is Coffin-Lowry syndrome more severe in?
Males
3 major features of Coffin-Lowry syndrome?
Profound ID, characteristic face, stimulus-induced drop episodes
Inheritance Cornelia de Lange Syndrome
AD
3 major features of Cornelia de Lange Syndrome
Short stature, abnormalities of bones in arms, ID/behavior problems, characteristic face
Inheritance of Costello Syndrome
AD (mostly de novo)
3 major features of Costello Syndrome
Development problems (FTT, DD), Heart problems (HCM), Characteristic face (curly/sparse hair)
People with Costello syndrome have risk for what kind of tumor
Rhabdomyosarcoma or neuroblastoma
Inheritance of Cri du Chat
Sporadic (usually)
Deletion in Cri du Chat is where?
5p
3 major features of Cri du Chat
High-pitched/cat-like cry, microcephaly, low birth weight
Inheritance of 22q11
Usually de novo
Where is deletion in 22q11?
22q11
3 major features of 22q11
Velopharyngeal incompetence, CHD, immune deficiency, increased risk for psych problems
Inheritance of DMD
XLR
3 major features of DMD
Muscle weakness and wasting– wheelchair by adolescence, cardiomyopathy, live into 20s
Inheritance of early-onset Alzheimer’s Disease
AD
3 major features of early-onset AD
Forgetfulness that interferes with daily life, needing help with personal care, may be personality/behaviour changes
Inheritance of Classic EDS
AD
3 major features of Classic EDS
Skin hyper extensibility, widened atrophic scars, joint hypermobility
Inheritance of hypermobile EDS
AD
3 major features of hypermobile EDS
Joint hyper mobility (complain of chronic pain), soft skin, absence of fragility
Inheritance of Vascular EDS
AD
3 major features of Vascular EDS
Arterial aneurysms, intestinal rupture, uterine rupture during pregnancy
Inheritance of Factor V Leiden Deficiency
Number of mutations influences risk
Inheritance of Familial Dysautonomia
AR
Unique features in Familial dysautonomia
Infancy- lack of tears, difficulty maintaining body temp; Kids- hold breath for long time; School age- bed wetting, reduced sensitivity to temperature changes/pain, BP regulation problems; Adult- walking problems, impaired kidney function
Inheritance of Crouzon Syndrome
AD
Inheritance of Apert Syndrome
AD
Inheritance of Pfeiffer Syndrome
AD
Inheritance of Muenke Syndrome
AD
3 major clinical features of Crouzon syndrome
Vrachycephaly, cervical spine anomalies, mild shortening of humerus/femora
2 major clinical features of Apert Syndrome
Brachycephaly, Mitten-type syndactyly of hands and feet
1 major clinical feature of Pfeiffer syndrome
Broad/angulated thumbs and great toes (also type 2- cloverleaf skull)
3 major features of Meunke Syndrome
Coronal synostosis, anomalies of hands and feet, hearing loss
Inheritance of Fragile X syndrome
XLR
Anticipation in Fragile X syndrome when passed through what parent?
Mom
3 major features of Fragile X
DD/ID, behaviour problems, dysmorphic face
Risks to Fragile X permutation carriers
FXTAS, POI
Premutation repeat number in Fragile X
55-200
Full mutation repeat number in Fragile X
200+
What trinucleotide repeat is expanded in Fragile X?
CGG
Inheritance of Friedreich’s Ataxia
AR
3 major features of Friedreich’s Ataxia
Ataxia, HCM, DM, scoliosis
What trinucleotide repeat is expanded in Friedreich’s ataxia
GAA
Premutation repeat number in Friedreich’s Ataxia
34-65
Full mutation repeat number in Friedreich’s Ataxia
66-1300
Inheritance of Hereditary Hemorrhagic Telangiectasia
AD
3 major features of HHT
Arteriovenous malformations, mucocutaneous telangiectasis, frequent nosebleeds
Inheritance of Hereditary Neuropathy with Liability to Pressure Palsies
AD
3 major features of HNLPP
Recurrent episodes of numbers, pain in limbs, carpal tunnel syndrome
Inheritance of HD
AD
Anticipation occurs in HD when passed through which parent?
Dad
3 major features of HD
Psych, Motor- chorea, Cognitive
Premutation repeat number in HD
27-35
Full mutation repeat number in HD
40+
What trinucleotide repeat is expanded in HD
CAG
Inheritance Incontinentia Pigmenti
XLD (lethal in males)
4 stages of skin problems in Incontinentia Pigmenti
Vesicular– verrucous– pigmentary– atrophic
Inheritance of Joubert Syndrome
AR (rarely XL)
3 major features of Joubert Syndrome
Molar tooth sign on MRI, episodes of usually fast/slow breathing, ataxia
Inheritance of Kabuki Syndrome
AD, XL
3 major features of Kabuki syndrome
DD, problems with hip/knee joints, Cleft palate, prominent finger pads
Inheritance of Kallman Syndrome
XL
3 major features of Kallman syndrome
Delayed/absent puberty, hypogonadotropic hypogonadism, anosmia
Karyotype of Klinefelter Syndrome
47, XXY
3 major features of Klinefelter Syndrome
Small testes, taller than peers, LD, behaviour problems
Inheritance of Krabbe Disease
AR
Enzyme deficiency in Krabbe disease
B-galactocerebrosidase
3 stages of features in infantile Krabbe
1: irritability/spasticity/FTT/dev arrest; 2: neurogeneration/seizures; 3: blind/deaf/unaware
Inheritance of Leber Hereditary Optic Neuropathy
mitochondrial
Major feature of LHON
Blurred/cloudy vision
Inheritance of LEOPARD Syndrome
AD
What does each letter stand for in LEOPARD Syndrome
Lentigines, Electrocardiographic conduction defects, Ocular hyperelorism, Pulmonary Stenosis, Abnormalities of Genitalia, Retarded growth, Deafness
Inheritance of Limb-Girdle Muscular Dystrophy
AR
3 major features of Limb Girdle Muscular Dystrophy
Weak thigh muscles, hypertrophy of calf muscles, cardiomyopathy in some
Loeys Dietz Inheritance
AD
3 major features of Loeys Dietz
Enlargement of aorta, arterial tortuosity, skeletal abnormalities, skin differences
Annual colonoscopy in Lynch syndrome to start at what age?
20-25 yo
Inheritance of Marfan Syndrome
AD
3 major features of Marfan Syndrome
Tall w/ arachnodactyly, ectopic lentil, aortic aneurysm
Inheritance of McCune Albright Syndrome
Not inherited-mosaicism
3 major features of McCune Albright Syndrome
Bone- polyostotic fibrous dysplasia, Skin- CALs with irregular borders, Endocrine- early puberty, thyroid goiter, acromegaly
Inheritance of Myotonic Dystrophy
AD
What trinucleotide repeat is expanded in Myotonic dystrophy
CTG
Premutation repeat number in Myotonic Dystrophy
35-49
Full mutation repeat number in myotonic dystrophy
>50
3 major clinical features of myotonic dystrophy
Progressive muscle weakness/wasting, cataracts, cardiac conduction defects
Inheritance of Nemalin Myopathy
AR (less often AD)
3 major features of Nemalin Myopathy
Myopathy of proximal muscles, feeding/swallowing problems, joint contractures
Inheritance of NF1
AD
6 major features of NF1
CALs, neurofibromas, inguinal/axillary freckling, optic glioma, Lisch nodules, distinct osseous lesion
Inheritance of NF2
AD
NF2 has growth of non-cancerous tutors, especially:
Vestibular schwannomas or acoustic neuromas
Inheritance of Noonan Syndrome
AD
5 major features of Noonan Syndrome
Short stature, heart defect- pulmonic stenosis, bleeding problems, skeletal malformations, males with delayed puberty
People with Noonan syndrome are at increased risk for what type of cancer
Leukemia
Inheritance of Parkinson’s disease
Sporadic (or AD or AR)
3 major features of Parkinson’s disease
Tremor, rigidity, braykinesia (can have psych conditions)
What gene is a risk factor for (but is not independently responsible for) Parkinson’s disease
LRRK2
Inheritance of Prayer Willi Syndrome
Sporadic
Where is deletion in Prader Willi Syndrome?
15p11-13
Etiologies for Prader Willi Syndrome?
Del of paternal 15p or maternal UPD of chromosome 15
3 major features of PWS
Intantile hypotonia and FTT, hyperphagia and obesity, hypogonadism
Inheritance of Cowden Syndrome
AD
Gene for Cowden Syndrome
PTEN
Increased risk for what cancers in Cowden syndrome?
Breast, endometrial, thyroid
Skin triad seen in Cowden syndrome
Facial trichillemommas, aural keratosis, papillomatous papules
Inheritance of Rett Syndrome
XLD (lethal in males)
3 major features of Rett syndrome
Developmental regression, hand wringing/clapping, seizures
Inheritance of Rubinstein-Taybi Syndrome
AD (most de novo)
3 major features of Rubinstein-Taybi Syndrome
ID, broad thumbs/first toes, eye/heart/kidney defects
People with Rubinstein-Taybi syndrome are at increased risk for what type of cancer?
Brain tumors, leukemia
Inheritance of Smith Magenis Syndrome
Sporadic
Where is deletion in Smith Magenis Syndrome
17p11.2
3 major features of Smith Magenis syndrome
DD/ID, Behaviour- self injury and lick/flip, sleep disturbances
Inheritance of Sotos Syndrome
AD (most de novo)
3 major features of Sotos Syndrome
Overgrowth in childhood, DD and behaviour problems, characteristic face
Inheritance of SMA
AR
3 major features of SMA
DD, unable to support head/sit unassisted, breathing and swallowing problems
What can modify the SMA phenotype?
Number of functional SMN2 copies
Inheritance of Syndromic Congenital Muscular Dystrophy
AR (sometimes AD)
3 major features of Syndromic Congenital Muscular Dystrophy
Muscle weakness at birth, delayed motor development with joint rigidity–> joint contractors, spinal deformities, respiratory compromise
Inheritance of Tay Sachs Disease
AR
3 major features of Tay Sachs Disease
Loss motor skills, seizures/regression, die in early childhood
Gold standard for diagnosis of Tay Sachs
HEXA enzyme analysis
Inheritance of Triploidy
Sporadic
Karyotype for triploidy
69, XXX
Triploidy usually a result of extra paternal or maternal chromosomes?
Paternal
Signs in pregnant woman of triploidy fetus with extra paternal set
Cystic placenta, partial mole, IUGR, syndactyly
Signs in pregnant woman of triploidy fetus with extra maternal set
Small placenta, IUGR
Inheritance of T13
Usually sporadic
Karyotype for T13
47, XX, +13
3 major features of T13`
Midline defects: HPE, polydactyly, CL+P
Inheritance of T18
Usually sporadic
Karyotype of T18
47, XX, +18
3 major features of T18
Hypertonia, clenched fist with overlapping fingers, rocker bottom feet
Sign in pregnancy of T18 fetus
Polyhydramnios
Inheritance of T21
Usually sporadic (4% Rob)
Karyotype of T21
47, XX, +21
3 major features of T21
Hypotonia, CHD, characteristic face
Inheritance of Tuberous Sclerosis
AD
Organ systems affected in Tuberous Sclerosis
Skin, Kidney, Lung, Heart, Brain
4 skin findings in Tuberous Sclerosis
Ash leaf spots, shagreen patches, facial angiofibromas, inguinal fibromas
What is in brain of Tuberous Sclerosis patient and how does it affect phenotype
Cortical Tubers; the higher the number the higher the cognitive impairment
Inheritance of Turner Syndrome
Sporadic
Karyotype for Turner Syndrome
45, X
3 major features of Turner Syndrome
Short stature, gonadal dysgenesis, CHD in half
What treatment should be given to girls with Turner Syndrome
Estrogen replacement therapy
What treatment should be given to boys with Klinefelter syndrome
Testosterone supplementation
Inheritance of VACTERL Syndrome
Sporadic (sometimes multifactorial)
What does each letter in VACTERL stand for?
Certebral facts, Anal atresia, Cardiac facts, Tracheo-Esophageal fistula, Renal anomalies, Limb anomalies
Inheritance of VHL
AD
Gene in VHL
VHL
What is the lifetime risk of renal cancer in VHL?
40%
What cancers are at an increased risk in VHL?
Renal, hemangioblastoma, pheochromocytoma
Ophthalmology exams start at what age for screening for VHL?
5 yo
CNS imaging by MRI is annual in screening for VHL, starting at what age?
11 yo
Inheritance of Waardenburg Syndrome
AD
3 major features of Waardenburg syndrome
SNHL, partial albinism/white forelock, blue eyes (or Dif color)
Inheritance of William’s Syndrome
Usually sporadic
Where is deletion in William’s Syndrome
7q11.23
3 major features of William’s Syndrome
Outgoing personality, Elfin face, Supravalvular aortic stenosis
Inheritance of Wilson’s disease
AR
What substance accumulates in tissues in Wilson’s disease
Copper
3 major features of Wilson’s disease
Liver disease with jaundice, movement disorders, Kayser-Fleischer rings, psych symptoms
Inheritance of Wolf-Hirschhorn Syndrome
Sporadic
Where is deletion in Wolf-Hirschhorn syndrome?
4p16.3
3 major features of Wolf Hirschhorn Syndrome
Delayed growth and development, ID, Greek Warrior helmet
Inheritance of Xeroderma Pigmentosum
AR
2 major features of Xeroderma Pigmentosum
Extreme sensitivity to UV rays from sunlight, progressive neurologic abnormalities
People with Xeroderma Pigmentosum have increased risk for what type of cancer?
Skin
Smokers with Xeroderma Pigmentosum have increased risk for what type of cancer?
Brain and Lung
Inheritance of XL Adrenal Hypoplasia Congenita
XL
3 major features of XL Adrenal Hypoplasia Congenital
Adrenal insufficiency- vomiting, hypoglycaemia; hypogonadotropic hypogonadism
Inheritance of XL Adrenoleukodystrophy
XLR
Major features of Xl adrenoleukodystrophy
Males have initially normal dev–behavior/attention changes–problems in school– loss of vision and comprehension, adrenocortical insufficiency
People with XL Adrenoleukodystrophy cannot metabolize?
Very long chain fatty acids (VLCFA)
Inheritance of WAGR syndrome
Sporadic
Genetic mutation in WAGR syndrome
Deletion of 11p
What does WAGR stand for?
Wilm’s Tumor, Aniridia, GU anomalies, Retardation- ID
What does WAGRO stand for?
Wilm’s Tumor, Aniridia, GU anomalies, Retardation- ID, Obesity
Inheritance of Kennedy’s Disease
XLR
Mutation in Kennedy’s Disease
CAG trinucleotide repeat expansion (>35)
3 major features of Kennedy’s Disease
Muscle weakness and wasting- cramps, difficulty walking, problems with feeding/swallowing; gynocomastia, infertility
Inheritance of Proteus syndrome
Not inherited- mosaic
3 major features of Proteus syndrome
Overgrowth, cerebriform connective tissue nevus on feet, ID, increased risk of pulmonary embolism
