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Genetic Counseling Boards Prep 2023 > Conditions > Flashcards

Conditions Flashcards

1
Q

What percentage of male with Fragile X syndrome have a diagnosis of autism spectrum disorder?

A

50-70%

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2
Q

What is the typical age of onset of Fragile X ataxia syndrome, and what is the molecular cause?

A

60-65 years (more common in males than females)
FX premutation: 55-200 repeats

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3
Q

At what range of CGG repeats in the Fragile X region are individuals at risk for POI and FXAS?

A

Premutation, 55-200

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4
Q

What are imaging and clinical signs consistent with Fragile X ataxia syndrome?

A

Imaging: MRI white matter lesions, MCP sign, brain atrophy
Clinical: tremor, gait ataxia, Parkinsonianism, memory issues, neuropathy

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5
Q

What percent of cases of autism spectrum disorder have Fragile X syndrome?

A

2-3%

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6
Q

What is the mean age of onset for Huntington’s disease, and what is the expected survival after diagnosis?

A

35-44 onset, median survival 15-18 years

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7
Q

What are the repeat ranges for Huntington’s disease?

A

CAG repeats
normal: <26
intermediate: 27-35
reduced penetrance: 36-39
full penetrance >40

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8
Q

Which symptoms of Huntington’s disease worsens with stress?

A

chorea

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9
Q

What percent of HD is juvenile onset (onset <age 20)?

A

5-10%, CAG repeats usually >60

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10
Q

What increases the stability of HD associated CAG repeat regions?

A

Interruption with CAA or CCG repeats

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11
Q

What primary symptoms are associated with Williams syndrome, and what is the deletion region?

A

7q11.23 deletion, usually de novo
delays/ID, endocrine, growth deficiency, cardiac, connective tissue

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12
Q

What is the specific cognitive profile associated with Williams syndrome?

A

strong in verbal short term language, weak in visuospatial
personality: empathetic, overfriendly, anxious with phobias/ADHD

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13
Q

What endocrine anomalies are associated with Williams syndrome?

A

early puberty, hypercalcemia, hypercalciuria, hypothyroidism, diabetes mellitus

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14
Q

What abnormality causes cri du chat syndrome?

A

5p deletion, usually de novo, 80-90% terminal deletions
80-90% of inherited are of paternal origin

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15
Q

What abnormality causes Wolff-Hirschhorn syndrome?

A

4p deletion

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16
Q

What percent of 22q deletions are inherited?

A

10% inherited, 90% de novo
except for nested deletions- 60% inherited

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17
Q

What symptoms are associated with Sotos syndrome?

A

distinctive facies, learning differences, overgrowth
behavioral (autism), advanced bone age, cardiac, cranial imaging anomalies, joint laxity, maternal pre-eclampsia, scoliosis, seizures

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18
Q

What gene causes Sotos syndrome and how often is this de novo?

A

NSD1, >95% de novo
In Japanese populations, 5q35 deletion is typical cause- less overgrowth, more severe learning issues

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19
Q

What region is associated with Beckwith Wiedemann syndrome and what are the percentage breakdown of causes?

A

11p15.5
55% imprinting defects
-50% loss of maternal methylation at IC2
-5% gain of maternal methylation at IC1
20% paternal UPD
5-10% CDKN1C variants (40% of familial cases)

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20
Q

What type of anomaly causing BWS is associated with cleft palate?

A

maternally inherited sequence variants

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21
Q

What type of anomaly causing BWS is associated with the highest risk of WT?

A

UPD 11, or maternal gain of methylation at IC1

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22
Q

What is the risk of neoplasia associated with BWS?

A

7.5%, concentrated in first 8 years of life

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23
Q

What are surveillance recommendations for children with BWS?

A

AFP every 2-3 months first 4 years of life (for hepatoblastoma)
abd US every 3 months until age 8
annual renal US age 8- adolescence
consideration of annual urinary calcium

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24
Q

What is the leading cause of morbidity/mortality for T21?

A

cardiac issues, especially in the first two years of life

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25
Q

What percentage of individuals with T21 have a CHD?

A

50%

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26
Q

What are the most common cardiac defects associated with T21 (%)?

A

40% AVSD- associated with the CRELD1 gene
32% VSD

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27
Q

Why do individuals with T21 have an increased risk of developing Alzheimer’s?

A

50-70% develop because there is an amyloid precursor protein in region

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28
Q

What is the penetrance of acute intermittent porphyria?

A

05.-1%

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29
Q

What percent of 21-hydroxylase CAH is salt wasting?

A

75% salt wasting, 25% simple virilizing

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30
Q

What laboratory elevations are seen with 21-hydroxylase CAH?

A

elevated 17-OHP and elevated adrenal androgens

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31
Q

What conditions can be associated with an Xp21 deletion depending on the exact region?

A

DMD/BMD, NR0B1 adrenal hypoplasia congenita, GK glycerol kinase deficiency

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32
Q

What are common symptoms of McCune Albright and what is the genetic cause?

A

coast of Maine CALs, fibrous dysplasia, endocrine- precocious puberty, excess CH, thyroid issues

caused by early embryonic post zygotic activating mutations in GNAS

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33
Q

What is the common HFE mutation, and what percent of homozygotes are symptomatic?

A

p.Cys282Tyr
28% symptomatic, 1% women pre menopause

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34
Q

What causes Hemophilia A?

A

Factor 8 deficiency
48% of severe cases due to inversion of introns 1 and 22

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35
Q

What causes Hemophilia B?

A

Factor 9 deficiency

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36
Q

How does severe beta thal present in the first two years of life?

A

with severe anemia and hepatosplenomegaly

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37
Q

What are laboratory findings of beta thal major?

A

microcytic hypochromic anemia, an abnormal blood smear with nucleated RBC

reduced HbA
increased HbF
normal HbA2
decreased MCV and MCH
decreased hemoglobin

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38
Q

What ethnic groups have a higher carrier frequency for beta thal and what are they?

A

Mediterranean (1/20)
Middle East/SE Asia (1/7)
African (<1/8)

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39
Q

What are symptoms of Hb Bart’s disease?

A

edema, CHF, severe anemia, hepatosplenomegaly, large placenta, death as neonate

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40
Q

What are common symptoms of alpha thal?

A

spleen enlargement, mild jaundice, bone changes, gallstones

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41
Q

What are laboratory findings of alpha thal major?

A

low MCV, low MCH, low HBA2, normal HbF
microcytic hypo chromic hemolytic anemia, moderate reticulocytosis, rarely nucleated RBC

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42
Q

What ethnic groups have a higher carrier frequency for alpha thal and what are they?

A

African (1/3)
Mediterranean
SE Asia (1/20)

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43
Q

What are common symptoms associated with untreated sickle cell disease?

A

vaso-occlusive events, chronic hemolytic anemia, acute and chronic pain, organ damage especially spleen

pain/swelling in hands and feet often first symptom

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44
Q

What is the top cause of mortality in individuals with sickle cell disease?

A

acute chest syndrome

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45
Q

What is the hemoglobin S allele?

A

HBB p.Glu6Val

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46
Q

What genes cause alpha thal, beta thal, and sickle cell?

A

alpha: HBA1, HBA2
beta: HBB
sickle cell: HBB p.Glu6Val homozygous

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47
Q

What are common symptoms of Bardet Biedl?

A

retinal rod cone dystrophy, obesity but normal birth weight, postaxial polydactyly, cognitive impairment, hypogonadotropic hypogonadism, renal malformations/disease

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48
Q

What are common manifestations of Meckel Gruber?

A

MKS genes
enlarged cystic kidneys, encephalocele, polydactyly, death before or shortly after birth

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49
Q

What are common symptoms of branchiootorenal syndrome?

A

ear malformations- branchial fistula and cysts, hearing loss, renal: mild hypoplasia- bilateral renal agenesis

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50
Q

What genes are associated with branchiootorenal syndrome?

A

EYA (40%), SIX1, SIX5

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51
Q

What are common symptoms of CHARGE syndrome?

A

coloboma
heart defect
choAnal atresia
retarded growth and development
genital hypoplasia
ear anomalies

cranial nerve, seizures, renal

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52
Q

What are common symptoms of Coffin Lowry syndrome?

A

delays, hypotonia, seizures, kyphoscoliosis, pectus, craniofacial

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53
Q

What are common symptoms of Cornelia de Lange syndrome?

A

facial findings, synophrys, high arched or thick eyebrows, growth restriction with prenatal onset, hypertrichosis, upper limb defects

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54
Q

What is the characteristic triad of Joubert syndrome?

A

molar tooth sign
hypotonia
dev delays

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55
Q

What chromosome region is associated with PAX6 related aniridia/WAGR syndrome?

A

11p13 deletion

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56
Q

What other anomalies can be seen in WAGR syndrome other than aniridia and WT risk?

A

genital anomalies
ID in 70%

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57
Q

What genes cause features of Miller Dieker deletion syndrome?

A

PAFAH1B1 (LIS1) - lissencephaly
YWHAE - other symptoms

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58
Q

What region causes Miller Dieker deletion syndrome?

A

17p13.3 deletion

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59
Q

What are characteristic features of Phelan Mcdermid syndrome?

A

hypotonia, severely delayed/absent speech, moderate-profound ID, large fleshy hands, dysplastic toenails, decrease perspiration

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60
Q

What are possible causes of Phelan Mcdermid syndrome?

A

22q13.3 deletion
SHANK3 mutations
ring chromosome 22- can include NF2 gene

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61
Q

What are the typical break points for Prader Willi syndrome?

A

BP1 or BP2 + BP3
8% with atypical deletion size

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62
Q

What are characteristic features of Rubinstein Taybi syndrome?

A

distinctive facies (low hanging columella, grimacing smile), broad thumbs, short stature, mod-severe ID

normal prenatal growth with rapid drop after birth

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63
Q

What are characteristic features of Smith Magenis syndrome?

A

coarse facial features, delays, cognitive, behavioral, sleep, abdominal obesity, self injurious behavior, sensory issues

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64
Q

What are possible causes of Smith Magenis syndrome?

A

17p11.2 deletion (90-95%)
RAI1 mutation (5-10%)

deletion can include FLCN –> BHD

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65
Q

What is the inheritance pattern of Oral-facial-digital syndrome type 1?

A

XLD, male lethal

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66
Q

What are characteristic features of oral-facial-digital syndrome?

A

tongue anomalies, clefts, hypodontia, dental, facial features, hand anomalies, polycystic kidneys, brain imaging findings

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67
Q

What is the de novo rate for achondroplasia?

A

80% (FGFR3)

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68
Q

What is the classic triad for cleidocranial dysplasia?

A

delayed closure of cranial sutures
hypoplastic or aplastic clavicles
dental anomalies

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69
Q

Which FGFR2 related syndrome has normal hands and feet?

A

Crouzon syndrome

Jackson Weiss- normal hands abnormal feet

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70
Q

What are the four main types of OI?

A

Type 1- classic non-deforming (most mild)
Type 2- perinatal lethal
Type 3- progressively deforming
Type 4- variable (moderate-mild)

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71
Q

What is the first and second leading causes of mortality for TSC?

A

first: CNS tumors
second: renal

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72
Q

What is the chance that a fetus with a cardiac rhabdomyoma has TSC?

A

75-80% risk for TSC

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73
Q

What is the inheritance pattern for hypohidrotic ectodermal dysplasia?

A

many genes, AR, AD
EDA- most common, XL

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74
Q

What leads to hypopigmentation in OCA?

A

impaired melanin synthesis

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75
Q

What percentage of individuals with NF1 have plexiform neurofibromas?

A

50%, mostly internal

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76
Q

What increases the likelihood that plexiform neurofibromas become malignant nerve sheath tumors?

A

whole gene deletion, high burden of plexiform neurofibromas

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77
Q

What is the de novo rate for NF1?

A

50%

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78
Q

What is the most common type of pathogenic mutation for neurofibromin?

A

severe truncating

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79
Q

What is the typical age of onset for NF2?

A

18-24 years

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80
Q

What is the de novo rate for NF2?

A

50%
- but 25-50% of de novo are mosaic

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81
Q

What type of NF2 mutations have more mild or more severe disease?

A

large deletions- more mild, no ID
nonsense and frameshift- severe

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82
Q

What percent of individuals with schwannomatosis have an affected parent?

A

<20%

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83
Q

What percent of sporadic cases of schwannomatosis have known cause?

A

40% known, 60% unknown cause (for sporadic)

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84
Q

What are the four stages of Incontinentia pigmenti?

A

birth- 4 months: blistering stage
several months: wart like rash
6 months- adulthood: swirling macular hyperpigmentation
adulthood:linear hypopigmentation

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85
Q

What is the de novo rate for IKBKG?

A

65%

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86
Q

What is the pregnancy outcome for a pregnant person who carries an IKBKG mutation?

A

33% affected female, 33% unaffected female, 33% unaffected male (because most affected males miscarry)

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87
Q

How can alpha 1 antitrypsin deficiency be diagnosed?

A

low serum concentration AAT + pathogenic variant or protein inhibitor typing

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88
Q

What is the carrier frequency for Alpha 1 antitrypsin?

A

2-3%
(1/43-1/50)

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89
Q

What provides a dx of cystic fibrosis?

A

elevated IRT on NBS, symptomatic, or fhx
+
evidence of abnormal CFTR: sweat chloride >60, biallelic variants, or nasal transmembrane potential differences

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90
Q

What cause cystic fibrosis related diabetes?

A

glucose metabolism is impaired due to loss of islet cells
–>absence of glucagon and insulinv

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91
Q

What can cause decreased fertility in females with CF?

A

pH imbalance and thickened cervical mucus

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92
Q

What is the expected CFTR genotype of a male with isolated congenital absence of the vas deferens?

A

severe LOF CFTR variant + non- CF causing variant
OR
two non-CF causing variants

93
Q

Which CF variant is most widely known to be targeted by mutation specific drugs?

A

Phe508del

94
Q

What is the most prevalent CFTR disease causing variant?

A

F508Del

(in N european, founder variant for Amish and AJ )

95
Q

Are CFTR pathogenic variants LOF or GOF, and how does this lead to disease?

A

LOF of transmembrane chloride channel

without chloride, sodium does not form salt and water is not attracted
–> thickened mucus

96
Q

How does the Poly T tract modify pathogenicity of CFTR variants?

A

thymidine bases in intron 8
7T and 9T benign

5T variably penetrant: decreases efficiency of intron 8 splicing
–>50% of full length CFTR produced

97
Q

How does the Poly TG tract modify pathogenicity of CFTR variants?

A

11, 12, or 13 TG
longer TG tract in cis with shorter poly T - more severe
–> reduced reduction of full length protein to 25%

98
Q

What are the four features of BPES?

A

blepharophimosis, ptosis, epicanthus inversus, telecanthus

99
Q

What are the two types of BPES?

A

type 1: four cardinal features + POI
(proteins truncated before polyalanine tract)

type 2: four cardinal features only

100
Q

What is the genotype/phenotype correlation with truncating variants in AR GJB2?

A

T/T - most likely profound hearing loss
NT/NT- most likely mild

101
Q

What is the GJB2 carrier rate in europeans?

A

2-4%
(1/25-1/50)

102
Q

What Hermansky Pudlak variants are most common in the Puerto Rican population?

A

80% HP is HPS1 duplication
20% HP is HPS3 deletion

103
Q

How are Pendred syndrome and non-syndromic enlarged vestibular aqueduct diagnosed?

A

PS: SNHL+ characteristic temporal bone on CT + euthyroid goiter

NSEVA: same without goiter

104
Q

What are the three variants most common with Leber hereditary optic neuropathy?

A

ND1 m.3460 G>A
ND4 m.11778 G>A (60-70% european)
ND6 m.14484 T>C (French Canadian, also has best long term visual outcome)

105
Q

What is the penetrance of LHON in males and females?

A

50% males
10% females

106
Q

What are three main types of Waardenburg syndrome?

A

Type 1: HL in 60%, distinguished by displacement of inner canthi
Type 2: multiple genes, MITF includes melanoma risk
Type 3: includes hypoplasia or contractures

107
Q

What is the de novo rate for Alagille syndrome?

A

50-70%

108
Q

What cardiac conduction anomalies are seen with Brugada syndrome?

A

ST segment abnormalities in leads V1-V3 on EKG
high risk for ventricular arrhythmias

109
Q

What is the mean age of SCD for Brugada syndrome?

A

40

110
Q

What percent of Brugada syndrome has an identifiable genetic cause?

A

~35%

111
Q

What are the dx criteria for HHT?

A

3 or more of:
-epistaxis
-characteristic telangiectasias
-visceral AVMs
-FDR

112
Q

What systems are affected in Holt Oram syndrome?

A

heart and hand syndrome

upper limb defects: absent thumbs-phocomelia, all with abnormal carpal bone
cong heart or cardiac conduction

113
Q

What is the difference in hearing loss between Usher type 1 and type 2?

A

profound in type 1
mild-moderate low, severe-profound high in type 2

114
Q

What are ocular findings in Stickler syndrome?

A

myopia, cataracts, retinal detachments

115
Q

What are hair and skin findings in Costello syndrome?

A

curly or sparse hair
soft skin with deep palmar and plantar creases
papillomata

116
Q

What is the tumor risk associated with Costello syndrome?

A

15% tumor risk
rhabdomyosarcoma, neuroblastoma, transitional cell carcinoma of bladder- usually seen in older adults!

117
Q

What is a characteristic skeletal finding in Costello syndrome?

A

ulnar deviation

118
Q

What percent of Noonan syndrome are affected with what types of heart disease?

A

CHD in 50-80%

20-50% PVS
20-30% HCM

119
Q

What is the risk of Noonan syndrome in a normal chromosome fetus with an increased NT?

A

3-15%

120
Q

What age do the characteristic skin findings of Noonan syndrome with multiple lentigines appear?

A

age 4-5, 1000s by puberty

121
Q

What cardiac findings are associated with cardiofaciocutaneous syndrome?

A

pulmonic stenosis, valve anomalies, septal defects, HCM, rhythym defects

122
Q

What are the hair and skin findings associated with cardiofaciocutaneous syndrome?

A

sparse, curly, fine or thick, wooly or brittle hair
cutaneous: xerosis, hyperkeratosis, icthyosis

123
Q

What causes cardiac arrest in long QT?

A

tdp self terminating –> syncope –> cardiac arrest or SCD

124
Q

What percent of individuals with long QT have an identified mutation?

A

80% identified variant
20% uknown

125
Q

What percent of individuals with long QT pathogenic variant have symptoms?

A

50% with pathogenic variants have symptoms

25% with pathogenic variant have normal EKG

126
Q

What is the risk of SCD with long QT syndrome?

A

6-8%

SCD is first sign in 10-15%

127
Q

What type of long QT is characterized by muscle weakness and facial dysmorphism?

A

type 7- Andersen Tawil

128
Q

What type of long QT is characterized by hand, foot, facial, and neurodevelopmental differences?

A

type 8- Timothy

129
Q

What are the characteristic cardiac findings of HCM?

A

unexplained L ventricular hypertrophy - wall thickness >15 mm

> 13 mm if fhx

increased risk for afib, SCD rare

130
Q

What are syndromic causes of HCM?

A

Fabry, Fredreich’s ataxia, TTR, Pompe, RASopathies

131
Q

What percent of individuals with HCM have sarcomeric mutations?

A

50-60% with fhx
20-30% no fhx

132
Q

What are characteristic cardiac findings of DCM?

A

L ventricular enlargement + systolic dysfunction

EF <50%

133
Q

What are syndromic causes of DCM?

A

Barth, DMD/BMD, carjaval, emery dreifuss, hemochromatosis

134
Q

How is hEDS diagnosed?

A

all three for clinical dx:
-joint hypermobility (Breighton score)
-syndromic features, musculoskeletal complications or fhx
-exclusion of other diagnoses

135
Q

How is the joint hypermobility in hypermobile type and classic EDS different from vascular EDS?

A

in hypermobile and classic the joint hypermobility is generalized

in vascular type the joint hypermobility is small joints

136
Q

How does ALS affected the lower and upper motor neurons?

A

upper: hyperreflexia, increased tone
lower: hyporeflexia, muscle atrophy

137
Q

How does ALS typically present?

A

with asymmetric focal weakness of the extremities

dx feature: hyper reflexia in segments and regions of muscle atrophy without sensory involvement

138
Q

When does CMT typically onset?

A

first- third decade with hand and feet involvement

139
Q

What is the age cutoff for DMD vs BMD?

A

wheelchair dependence <13 for DMD
>16 for BMD

140
Q

What are causes of mortality for DMD?

A

respiratory
cardiac (20%, 50% for BMD)

141
Q

What is the typical onset for Freidreich’s ataxia?

A

slowly progressive ataxia <25
typical onset 10-15

142
Q

What are symptoms of Freidreich’s ataxia?

A

dysarthria, weakness, spasticity, scoliosis, bladder dysfunction, absent lower limb reflexes, loss of position/vibration sense
2/3 HCM
30% diabetes

143
Q

What is the onset of nemaline myopathies?

A

congenital onset

144
Q

What systems are affected by myotonic dystrophy type 1?

A

skeletal and smooth muscle, eye, heart, endocrine, CNS

145
Q

Is CK elevated in Myotonic dystrophy type 1?

A

only mildly elevated if symptomatic

146
Q

What the SMA types?

A

type 0: prenatal
type 1: dx < 6 months, sit with support only
type 2: dx 6-18 months, can sit independently
type 3: dx >18 months, independent ambulation

147
Q

What is the most common cause of death in SMA?

A

respiratory failure

148
Q

What is the typical onset of ataxia telangiectasia?

A

progressive cerebellar ataxia at 1-4

149
Q

What is the triad associated with septo optic dysplasia?

A

absent septum pellucidum
optic nerve hypoplasia
pituitary dysfunction

150
Q

What are features commonly associated with Alagille syndrome?

A

paucity of bile ducts, posterior embryotoxon, liver, cardiac, kidney, facial findings

151
Q

Are most RASopathies GOF or LOF?

A

GOF

152
Q

Which RASPopathies are not GOF?

A

NF1 and SPRED1 are LOF
-they are negative pathway regulators, so down-regulating them up regulates

153
Q

Which RASopathy can be characterized by papillomata and deep plantar creases?

A

Costello syndrome

154
Q

Which RASopathy can be characterized by eczema, heart deefects, and coarse features?

A

cardiofaciocutaneous syndrome

155
Q

What type of SCA has visual impairment?

A

type 7

156
Q

Is expansion more likely in paternal or maternal transmission of SCAs?

A

paternal transmission more likely for expansion

157
Q

What is the classic triad of dyskeratosis congenita?

A

dysplastic nails, lacy reticular pigmentation, oral leukoplakia

also with bone marrow failure, pulmonary fibrosis

158
Q

What are common features of Treacher Collins?

A

craniofacial findings with malar hypoplasia, ear anomalies and hearing loss, normal intelligence, colobomas

159
Q

What types of ocular findings are seen in Stickler syndrome?

A

myopia, cataracts, retinal detachments

160
Q

What are common findings in Kabuki syndrome?

A

significant postnatal growth deficiency, characteristic facies, CHD in half, fetal finger pads

161
Q

What are expected laboratory findings for Smith Lemli Opitz?

A

low cholesterol and high precursor

162
Q

What are common findings in individuals with Zellwegger syndrome?

A

cerebro-hepato-renal
abnormal VLCFA
hypotonia, growth, facies, limb, liver, stippling of bones
often fatal in first year

163
Q

Do carrier females of EDA1 have symptoms?

A

90% with dental or sweating anomalies

164
Q

Is maternal or paternal expansion of FMR1 more likely to expand?

A

maternal expansion more likely

165
Q

What percent of male or female FMR1 premutation carriers >50 have symptoms?

A

40-50% males
8-17% females

166
Q

What percent of individuals with Marfan syndrome have ectopic lentis?

A

50-80%

167
Q

How is Marfan syndrome dx?

A

FBN1 variant + aortic root enlargement OR ectopic lentis

168
Q

What is the systemic score cutoff for Marfan syndrome?

A

> =7

169
Q

What causes immunodeficiency in 22q?

A

thymic hypoplasia

170
Q

What causes hypocalcemia in 22q?

A

hypoplasia of the parathyroid gland

171
Q

What type of testing is most appropriate for 22q?

A

MLPA or CMA over FISH

172
Q

What are typical breakpoints for 22q?

A

A and D, nested deletion is smaller
*TBX1 located between A and B

173
Q

What causes polyhydramnios in 22q?

A

palate anomalies

174
Q

What can cause 22q to show up on NBS?

A

low T cells on NBS

175
Q

What is the appropriate next step for an individual with CF when R117H is identified?

A

reflux to poly T

176
Q

What percent of individuals with CF have a F508del allele?

A

90%

177
Q

What type of CFTR variants have some low vs some residual function?

A

those that affect folding, splicing, or transcription have low function

those that affect stability, activity, or conductance have some residual function

178
Q

What is the next step if an individual is identified with 1 or 2 CFTR variants after an elevated IRT?

A

sweat test

95% with an elevated IRT and 1 variant only have a negative f/u sweat test

179
Q

What is the next step if an individual is identified with 0 CFTR variants after an elevated IRT?

A

if very high IRT than still do a sweat test

180
Q

How is cutis laxa characterized?

A

loose redundant skin, arterial toruosity and aneurysms, dicerticula of the colon or bladder - UTIs, pulmonary emphysema

ID if CDG disorder

181
Q

What are acquired causes of HCM?

A

hypertension, aortic stenosis athletic training

182
Q

What are triggers of LQT Type 1?

A

75% exercise
15% emotion
10% sleep

183
Q

What are triggers of LQT Type 2?

A

63% sleep
37% emotion

184
Q

What are triggers of LQT Type 3?

A

80% sleep
15% emotion
5% exercise

185
Q

Which types of LQT are LOF or GOF?

A

Type 1- KCNQ1 - LOF
Type 2- KCNH2 - LOF
Type 3 - SCN5A - GOF

186
Q

What are triggers of CPVT?

A

stress, syncope

187
Q

What percent of families with HCM have identified pathogenic variants?

A

20-40%

188
Q

What are common findings of myotonic dystrophy type 1?

A

facial weakness, balding, distal weakness, foot drop, frequent falls, sleep disturbance, premature cataracts, cardiac conduction anomalies, cognitive/apathy, endocrine- thyroid, diabetes

189
Q

What is the characteristic triad of Emery dreifuss sydrome?

A

joint contractures, slowly progressive weakness, cardiac anomalies

190
Q

What are the genetic testing recommendations for epilepsy?

A

genetic testing recommended for all unexplained epilepsy

panel or WES (preferred) then array

191
Q

What percent of individuals with DMD have delayed motor milestones?

A

42%

192
Q

What is the risk for DCM in carriers of DMD?

A

5-8%

193
Q

How does myotonic dystrophy affect fertility?

A

decreased fertility in males

194
Q

How does onset differ in myotonic dystrophy type 1 vs type 2?

A

type 1: variable depending on number of repeats
type 2: usually adult onset, repeat size does not correlate with onset or severity

195
Q

What systems are affected in XL adenreoleukodystrophy?

A

adrenal glands and CNS

196
Q

What percent of female carriers of XL ALD have symptoms, and at what age?

A

20% with spastic paraparesis in middle age or later
-adrenal function usually preserved

197
Q

What symptom is less common in juvenile onset Huntington’s?

A

chorea

198
Q

What is the general population risk of Alzheimer’s?

A

11% > 65
33% > 85

199
Q

When is the onset of bone marrow failure in fanconi anemia?

A

first decade of life

200
Q

What is the risk for AML in Fanconi anemia?

A

13% by age 50

201
Q

How is chromosome breakage tested for Fanconi anemia?

A

cytogenetic testing of lymphocytes treated with DEB And mitomycin C

–> chromosome breakage and radial forms

202
Q

Most causes of Fanconi anemia are AR, what are AD and XL causes?

A

AD: RAD51, usually de novo
FANCB: XL

203
Q

What are laboratory findings associated with fanconi anemia?

A

macrocytosis, increased Hf (precedes anemia), cytopenia

204
Q

What are prenatal and perinatal findings of Angelman?

A

none, normal pregnancy and birth

205
Q

What percent of genetic causes of Angelman are picked up on DNA methylation?

A

80%, detected deletions, UPD, or imprinting defects
-also detected on MLPA
-FISH only detects the deletion

206
Q

What genetic cause of Angelman syndrome has the most severe phenotype?

A

deletion

207
Q

Which of the genetic causes of Angelman syndrome is sometimes mosaic?

A

20% imprinting defects are mosaic - may have some speech vs none

208
Q

What cause of Angelman syndrome has a nearly 100% recurrence risk?

A

if father has a 15;15 Robertsonian translocation
(50% if mother has a 15;15)

209
Q

What percent of UBE3A mutations causing Angelman are inherited?

A

30% (maternally inherited)

210
Q

What are the most common breakpoints causing Angelman syndrome deletions?

A

50% BP2-BP3
40% BP1-BP3

211
Q

What does CADASIL stand for?

A

cerebral AD arteriopathy with subcortical infarcts and leukoencephalopathy

212
Q

How is the onset of CADASIL characterized?

A

mid adult onset of recurrent strokes

cognitive decline, migraines, mood, apathy

213
Q

What is the typical duration of Alzheimer’s disease before death?

A

8-10 years

214
Q

What are neurological findings of a brain affected by Alzheimer’s disease?

A

beta amyloid plaques (plaque are negative for prion disease), intraneuronal neurofibrilliary tangles including tau protien, amyloid angliopathy

215
Q

What is the risk of Alzheimer’s disease if a FDR is affected?

A

20-25%

216
Q

What is a CK for an individual with FSHD?

A

normal to mildly elevated

217
Q

When is the typical onset of FSHD?

A

teens

218
Q

When is the onset of Wilson’s disease?

A

childhood-40

219
Q

What is the characteristic triad of septo-optic dysplasia?

A

optic nerve hypoplasia, abnormal midline structures of the brain, pituitary hypoplasia

220
Q

What proportion of Alport syndrome is XL?

A

2/3

221
Q

What is a characteristic immunostaining finding for Alport syndrome?

A

absence of immunostaining for collagen chains

222
Q

What genetic causes of Alport syndrome are more likely to have earlier onset ESRD?

A

large rearrangements, nonsense, frameshift

223
Q

What specific genetic cause of Alport syndrome is associated with an increased risk for diffuse leiomyomatosis?

A

large deletion at adjacent 5’ end encompassing COL4A5 and COL4A6

224
Q

What is the risk of ESRD by age 60 for individuals with ADPKD?

A

50%

225
Q

What is a common prenatal finding for individuals with RSS?

A

asymmetric prenatal growth restriction

226
Q

What percentage of individuals with RSS have an identified genetic cause?

A

60%
40% no identified cause

227
Q

What are the six clinical criteria for RSS? How many are needed for a clinical dx without a genetic cause?

A

SGA
postnatal growth failure
* relative macrocephaly at birth *
* frontal bossing or prominent forehead *
body asymmetry
feeding difficulties

No genetic cause:
-4 criteria met including two **
-other causes ruled out

228
Q

How does hypermethylation of the ICR1 region lead to the RSS phenotype?

A

hypermethylation of ICR1
–> biallelic H19 expression
–> biallelic silencing of IGF2
–> growth restriction

229
Q

What are typical laboratory findings in SLO?

A

deficiency of 7 dehydro cholesterol reductase causes:

elevated 7 DHC
low serum cholestero;

Genetic Counseling Boards Prep 2023 (13 decks)

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