Genetics Flashcards
(161 cards)
1
Q
Pattern: Lens dislocation upward
A
Marfan
2
Q
Pattern: Lens dislocation downward
A
Homocystinuria
3
Q
Cardiac problems assoc with Marfan
A
aortic root dilation, aortic rupture, mitral valve prolapse
4
Q
- Fibrillin on chromosome 15
A
Marfan
5
Q
- TFBR1/2
A
Marfan 2 and Loeys-Dietz
6
Q
NF criteria: 2/7
A
- > 6 cafe au lait >5mm prepub, >15mm prepub
- 2+ neurofibromas
- 2+ lisch nodules of iris
- OPG
- inguinal or axillary freckling
- sphenoid wing dysplasia or thinning of long bone cortex
- 1st degree relative with NR
7
Q
Pattern: coarse facies, corneal clouding, organomegaly, cogntive loss
A
Hurler features
8
Q
- alpha-1 iduronidase
A
Hurler genetics
9
Q
Muscle weakness and progression pattern of DMD
A
symmetric proximal symmetric myopathy, symptoms prior to 5, can’t walk by 13
10
Q
Majority of DMD mutation
A
deletion and point mutations
11
Q
Pattern: coarse facies, hump on back, short stature, cognitive loss, gibbus organomegaly, clear cornea
A
Features of Hunter
12
Q
Phenotype of x-linked dominant
A
Rett - girls only because boys die
13
Q
IHP of Hunter
A
x-linked recessive
14
Q
Gene mutation in MELAS
A
tRNA genes
15
Q
Genetic mutation type in myotonic dystrophy
A
trinucleotide repeats
16
Q
Genetic mutation type in Fragile X
A
trinucleotide repeats
17
Q
Pattern: puffy hands and feet in baby
A
Turner
18
Q
Pattern: horseshoe/ectopic kidney, hearing loss, hypothyroidism
A
Turner
19
Q
Hormonal abnormality of Turner
A
hypothydroidism
20
Q
Congenital heart disease in Turner
A
Coarctation, bicuspid aortic valve, hypoplastic left heart
21
Q
Late onset heart disease in Turner syndrome
A
aortic dissection (increased during pregnancy), HTN
22
Q
Genetics of Wolf-Hirschhorn syndrome
A
4p deletion
23
Q
Pattern: severe retardation, cleft lip/palate, FTT CHD, microcephaly, flat nasal bridge with high arched eyebrows
A
Wolf-Hirschorn
24
Q
Cri du chat syndrome
A
5p delection
25
Pattern: low birth weight, ID, epicanthal folds, CHD, 5p-
Cri du chat
26
Pattern: Full lips, smooth philtrum, stellate iris, puffy eyes, bitemproal narrowing, elfin facies, cocktail party, hypercalcemia, supravalvular aortic stenosis, developmental delay
Williams
27
Genetic deletion in Williams
7q11.23
28
Pattern: bulbous nose, congenital, thymus hypoplasia, cleft palate, hypocalcemia
22q11.2 - DiGeorge
29
Pattern: hirsuitism, unibrow (synophyrs), limb anomalies, microcephaly, oligodactyly,
Cornelia de Lange
30
Genetics of Cornelia de Lange
NIPBL, 5p13
31
Pattern: small mandible, malar hypoplasia, down slanting palpebral fissures, malformed ears with hearing loss, lower eyelid coloboma
Treacher collins syndrome
32
Genetics of Treacher Collins syndrome
5q32, treacle
33
What skin/musculoskeletal finding with fragile X
flat feet, loose joins, soft smooth skin
34
what cardiac condition
Mitral valve prolapse
35
What GU problem associated with Fragile X
Macro-orchidism
36
neuro issue with fragile x syndrome
neuronal migration defects
37
Lay out plan for eval of pt with Fragile X
Echo - MVP
Vision - strabismus
Eval for loose joints and possible seizures
38
Adult female/male with pre-mutation of FRM1 CGG repeat will have what symptoms
Female - premature ovarian function
| Male - tremors
39
Pattern: neonatal hypotonia, poor feeding, FTT, DD, almond shaped yes, small hands and feet, obesity and feeding problem, microfallus
Prader-Willi syndrome
40
Genetics of Prader-Willi syndrome
Paternal 15q deletion
Uniparental disomy chromosome 15
Mutation in imprinting gene
41
Genetics of Angelman syndrome
Deletion of maternal chromosome 15, paternal uniparental disomy, imprinting gene mutation
42
Pattern: brushfield spots
T21
43
Endocrine and GI problems in T21
hypoTH, duodenal atresia
44
What other variant of genetics can be seen in T21?
Robertsonian translocation in 5%
45
Pattern: Thin upper lip, philtrum, ID, microcephaly, down-slanting palpebral fissures
FAS
46
Pattern: Microfallus, hypotonia, depressed nose bridge, fusion of 2/3 toe (syndactylyl), undescended testes
Smith-Lemli-Opitz
47
* in Smith-Lemli-Opitz
* delta-7-sterol reductase, cholesterol biosynthesis
48
Pattern: low serum cholesterol level, elevated 7-dehydrocholeterol
Smith-lemli-opitz
49
Rx for Smith-Lemli-Opitz
diet high in cholesterol, which only improves condition
50
Dx associated with conotruncal heart defect such as transposition, TOF, interrupted aortic arch, truncus arteriosus
22q deletion syndrome
| DiGeorge or velocardiofacial syndromes
51
Dx supervalvular aortic stenosis
Williams
52
Dx AV canal
Down
53
Dx pulmonary valve stenosis, HOCM
Noonan
54
Dx coarctation of aorta
Turner
55
Pattern: short stature, ptosis, broad or webbed neck, heart defect, shield chest, developmental delay
Noonan
56
Dx dilated aortic root
marfan
57
Pattern: growth deficiency, microcephaly, prominent occiput, small mouth/small jaw, short sternum, cardiac anomalies, cryptorchidism, rocker bottom feet, hypoplastic nails,
Tri18
58
Pattern: microcephaly, holoprosencephaly, low birth weight, scalp ulceration, iris coloboma, cardiac anomalies, renal and genital anomalies, cleft lip and palate, polydacyly, rocker bottom feet
Tri13
59
Pattern: wormian bones, bowing of the long bones, small chest bones, blue sclera
Osteogenic imperfect type 2
60
* OI type 2
AD mutation in COL1A1 and COL1A2
61
Cause of mortality in OI type 2
inability to ventilate, intracranial hemorrhage
62
Pattern: triangular head, most common neonatal skeletal dysplasia, cloverleaf skull, short limb dwarfism, severe brain malformations, mutations in FGFR3
thanatophoric dysplasia
63
Pattern: short stature, extra fold in proximal limbs, chest triangle, frontal bossing, trident hand, small foramen magnum
achondroplasia
| * mutation in FGFR3 AD
64
Complications of achondroplasia
increased risk for SIDS, small foramen magnum-risk of hydrocephalus or c-spine injury, small thorax-risk for pneumonia
65
Pattern: long fingers, lens dislocation, myopia, high arched palate
Marfan
66
Management of Marfan
Annual ECHO, ACE inhibitors to prevent aortic dilation, ophthalmologic exam, rule out homocystinuria
67
* for craniosynostosis
FGFR1, FGFR2, FGFR3, TWIST, MSX1
68
Syndromes most commonly associated with craniosynostosis
Pfieffer, Cruzon, Apert
69
Management of craiosynostosis
Referral to craniofacial team, early referral to ophtho, make sure airway isn't compromised from small midface
70
small mandible --> cleft palate --> glossoptosis
Pierre-Robin sequence
71
Small mandible --> cleft palate --> glossoptosis + retinal detachment, myopic, and hearing loss
Pierre-Robin syndrome - Stickler syndrome
72
Pattern: omaphalocele, crease or pits in ear lobe, large size, neonatal *hypoglycemia*, macroglossia, umbilical hernia
Beckwith-Wiedemann syndrome
73
What tumors do Beckwith-Wiedemann syndrome
Wilms, adrenal cortical carcinoma, hepatoblastoma
74
Pattern: aniridia and intellectual disability, Wilms tumor, gonadoblastoma
Aniridia-WAGR syndrome
75
Mutation in WAGR-syndrome
Deletion chromosome 11p13
76
Tumor associated with hemihyperplasia
Wilms, adrenal cortical carcinoma, hepatoblastoma
77
Management for Beckwith-Wiedemann syndrome, hemihyperplasia, or WAGR
q3 month abdominal US for kidney, adrenals, and liver until age 8, q3 alphafetoprotein until age 4
78
Evaluation for infant with hearing loss
Audiology, ENT (outer or inner ear), genetics, TORCH testing (CMV), ophtho, EKG (conduction problem)
79
Pattern: hyperextensibility, atrophic scars, delayed walking
Hypermobile Ehlers Danlos Syndrome
80
Pattern: hypermobile, spontaneous gut rupture, aneurysm, wound dehicience
Ehlers Danlos Syndrome
81
What syndromes have radial ray anomalies
TAR, Diamond blackfan anemia, fanconi anemia, holt-oram syndrome, VATER/VACTERL
82
What evaluation do you for child with radial ray anomalies
chromosome breakage studies
83
Pattern: absent clavicles, delayed closure of the fontanelle, skeletal dysplasia
cleidocranial dysostosis
84
Testing for kids suspected of Autism
Fragile X syndrome, microarray
85
mutations associated with Autism
16p11.2 deletion and 15q11-q13 duplication
86
X-linked genes associated with autism
Neuroligins NLGN3, NLGN4
87
Test for FA oxidation dx
plasma acylcarnitines
88
Test for peroxisomal dx
VLCFA
89
Test for mucopolysaccharidoses
urine glycosaminoglycan
90
Pattern: fine first few days of life, then lethargy, tachypnea in the latter half of first week of life
Urea cycle deficit
91
Pattern: hyperammonemia and alkalosis
urea cycle disorder
92
Pattern: hyperammonemia and acidosis
organic acidemias
93
Pattern: hyperammonemia, ketosis, neutropenia, hyperammonemia
organic acidemias
94
Test for organic acidemias
urine organic acids
95
Pattern: hyperammonemia and hypoglycemia
FA oxidation dx
96
Pattern: hyperammonemia and normal anion gap (3-11),
urea cycle disorder
97
Pattern: hyperammonemia and high anion gap >11
organic acid disorder
98
Management of hyperammonemia
Administer calories to prevent catabolism, D10 with insulin, urea cycle scavengers (sodium benzoate, phenybutyrate bypass the urea cycle, dialysis in severe cases (>500mmol/L)
99
Pattern: infant male, low BUN, high urine orotic acid, abnormal plasma aa (low citruliine)
OTCD
100
Rx for urea cycle disorders
dialysis, scavengers (by pass the urea cycle), blude. long-term treatment insluced protein restriction, special formula and outpt scavenger therapy
101
Name 3 most common organic acidurias
isolveric, methmalonic, proprionic
102
Pattern: acidosis, hyperammonemia, pancytopenia, ketosis, MR
organic acidurias
103
Pattern: sweaty sock smell
isovaleric
104
May confused with cobalamin deficieincy
methylmalonic acidemia
105
Biotin is a cofactor for this catabolism
Proprionic acidemia
106
Ketotic hypoglycemia + increased lactate
glycogen storage disease type 1
107
Ketotic hypoglycemia + normal lactate
other than GSD1, ketotic hypoglycemia itself or endocrine problems
108
Ketotic hypoglycemia + hepatomegaly, increased lactate
hereditary fructose intolerance
109
Ketotic hypoglycemia + reducing substances, liver disease and E. coli sepsis
galactosemia
110
Nonketotic hypoglycemia + presents after fasting
FAOD
111
Nonketotic hypoglycemia + hypoglycemia even when feeding normally
hyperinsulinism
112
Nonketotic hypoglycemia + large macroglossia, umbilical hernia
Beckwith Wiedemann syndrome
113
Pattern: hepatomegaly, hypoglycemia, cherubic or doll-like facies, growth impairment
Hepatic type glycogen storage
114
Rx for hepatic type glycogen storage
cornstarch, nocturnal enteral feeding, liver transplant
115
Pattern: renal disease, bleeding diathesis, lactic acidosis, hyperuricemia, hypertriglyceridemia
Von Gierke glucose 6-phosphatase
116
Pattern: renal disease, bleeding diathesis, lactic acidosis, hyperuricemia, hypertriglyceridemia, mucosal ulcerations (oral, intestinal, vaginal), and neutropenia
Glycogen storage Ib glucose 6-phosphate transporter
117
Pattern: hypoglycemia, skeletal myopathy, cardiomyopathy, hyperlipidemia, elevated transaminases
Glycogen storage III cori /Forbes
118
Pattern: hypoglycemia, severe FTT, progressive cirrhosis
GSD IV
119
Pattern: muscle pain and cramping, exercise intolerance, progressive weakness, rhabdomyolysis, no lactate with exercise
McArdle V
120
Pattern: like McArcle, but earlier onset and more severe, compensated hemolytic anemia, exercise intolerance worse after high carb meal
Muscle type glycogen storage Tarui VII
121
Pattern: hypoketotic hypoglycemia, liver disease, and mild hyperammonemia, may cause sudden death
MCAD FAOD
122
Pattern: Hypoketotic hypoglycemia, liver disease, sudden death, cardiomyopathy, rhabdomyolysis, retinopathy
LCFA dehydrogenase
123
Rx for FAOD
fasting avoidance, low fat diet, MCT for LCD, but not for MCAD
124
Pattern: E. coli sepsis in 7 day old, irritable, lethargic, jaundiced, hypoglycemia, and hepatomegaly, cataracts
Galactosemia
125
Dx for galactosemia
decrease in GALT activity, increase in galactose 1-phosphate levels
126
Pattern: hepatomegaly, jaundice, hepatic failure, hypoglycemia, hypophosphatemia, lactic acidosis
hereditary fructose intolerance (fructose 1-phosphate aldolase deficiency)
127
Pattern: liver failure, coagulopathy, jaundice, renal tubular acidosis, cabbage-like odor
tyrosinemia type 1
128
Pattern: corneal dystrophy, erosions and ketosis of palms and soles, MR
Tyrosinemia type II, oculocutaneous
129
Hyperammonemia + acidosis + ketosis
organic acidemia
130
Hypoglycemia + acidosis - ketosis
Fatty acid oxidative disorder
131
Hypoglycemia + ketosis + lactic acidosis
GSD or Hereditary fructose intolerance
132
Very high lactate without hypoxia or other causes
mito, pyruvate dehydrogenase deficiency
133
Pattern: early macrocephaly and subtle neuro signs, after viral infection has basal ganglia stroke and MR and movement disorder; retinal or subdural hemorrhages and mistaken for child abuse
Glutaric academia type 1
134
Pattern; acidosis and metabolic decompensation, severe ID, rash and alopecia
biotinidase deficiency, organic acidemia
135
Pattern: ketosis, possible hypoglycemia, no hyperammonemia or acidosis, poor feeding, apnea, lots of leucine, seizures, death, ataxia or DD
MSUD
136
Rx for MSUD
thiamine, dialysis to remove leucine, protein restriction
137
Pattern: abnormal startle, cherry red spot, decrased attentiveness at 3 to 6 months, progressive neuro decline
Tay Sachs
138
Pattern: Bone and CNS, osteopenia, osteonecrosis, fractures, hepatosplenomegaly, anemia, thrombocytopenia, coagulopathy, pulmonary disease, CNS involvement, swallowing difficulty, nystagmus, seizures
Gaucher
139
Dx for Gaucher
Leukocyte active, gaucher cells (macrophages)
140
Pattern: Angiokeratosis, pain crisis in distal extremities, left ventricular hypertrophy, and cardiomyopathy, strokes, proteinuria, and renal disease
X-linked disease
141
alpha-galactosidase A
Fabry
142
Glucocerebrosidase deficiency
Gaucher
143
Leucine toxicity
MSUD
144
Abnormal lysine and tryptophan
glutaric academia type 1
145
alpha-glucosidase
Pompe
146
Pattern: infant with feeding problems, severe weakness, cardiomyopathy, early death
Pompe
147
Pattern: child with muscle weakness progressing to resp failure in several years
Pompe
148
Alpha L-iduronidase
Hurler
149
Pattern: early onset, corneal clouding, die first 10 years
Hurler
150
Pattern: course facies, no corneal clouding
Hunter
151
Iduronate sulfatase x-linked
Hunter
152
Pattern: course facies, brain problems > bone
San Fillipo
153
Pattern: course facies, skeletal dysplasia
Morquio
154
Pattern: course facies, normal intelligence, short, joint problems
Maroteaux-Lamy
155
Pattern: long slender figures, long limbs, pectus, lens go down, thrombosis, strokes
Homocystinuria
156
Pattern: hypotonia, seizures, liver dysfunction, triangular head
Zellweger
157
Pattern: microcephaly, broad nasal tip, cataracts, 2-3 toe syndactyly, polydactyly, cleft palate, CHD, autism, MR
Smith-lemli-optiz
158
Urine glcyosaminoglycans
mucopolysaccharidoses
159
Plasma acylcarnitine
fatty acid oxidation disorders
160
Organic acid disorders
urine orgnanic acids
161
Components of newborn screening
PKU, galactosemia, hypoth, SCD, biotin, hemoglobinopathies, amino acidopathies, organic acidurias, FA osication
