ABGC Exam Prep with Complete Solutions
22q11.2 deletion syndrome (aka DiGeorge) - ANSWER-1:1-2000 - most common
microdeletion
2nd most common cause of CHD after DS
Contiguous gene deletion syndrome
AD deletion of 22q11.2 (~50 genes in this region)
10% familial mutations
Detected by: FISH, microarray, MLPA
Clinical features:
Endocrine: hypocalcemia, short stature, hyperparathyroidism
Cardiac: tetralogy of fallot, truncus arteriosus
Immunodeficiency: thymic atrophy
Palate: CL+/-P, velopharyngeal insufficiency
Psychiatric: schizophrenia, bipolar disorder, anxiety, depression
DD/ID, seizures, SNHL
GI/GU anomalies, malignancy (Wilms), skeletal issues (scoliosis)
ACE inhibitor - ANSWER-renal tubular acidosis → potter sequence, IUGR
Achondroplasia - ANSWER-~1/15-40,000
AD: FGFR3
~80% de novo; associated with APA
~98% 1138G>A
Homozygous mutations are lethal
Clinical features
Rhizomelic shortening, short stature, trident hands, brachydactyly, macrocephaly,
frontal bossing, mid-face hypoplasia, lumbar lordosis/kyphosis, genu varum, foramen
magnum stenosis, normal IQ
AD Polycystic Kidney Disease - ANSWER-Late onset bilateral renal cysts, cysts on
liver, seminal vesicles, pancreas, arachnoid membranes, intracranial aneurysm, dilation
of the aortic root, dissection of the thoracic aorta, mitral valve prolapse, abdominal wall
hernia
50% will have end stage renal disease by age 60
Unilateral enlarged kidney
Presenting symptom is flank pain, hematuria
US detection ~10% of the time
AD PKD1 (85%) PKD2 (15%)
1 in 1000
Adrenoleukodystrophy - ANSWER-XL: ABCD1 [pseudogenes]
1:20-50,000 males; female carriers can have neurological symptoms
Toxic build-up of VLCFAs
Most affected tissues: myelin, adrenal cortex, leydig cells of testes
Three clinical forms:
,Addison's: onset child-adult - only adrenal insufficiency, fertility issues
Adrenomyeloneuropathy: onset 20-30s - progressive stiffness/weakness, some adrenal
insufficiency
Cerebral form: onset child-adolescence - rapidly progressive, severe cognitive &
neurologic disability, impaired adrenal function, die within 2-5 y of diagnosis
Treatment: Lorenzo's oil, HSCT in early patients, diet w/o VLCFAs, HRT
advanced empathy - ANSWER-Purpose: counselor response goes beyond what the
client expresses and goes into inner thoughts and feelings, usually occurs late in a
session
Content level: deals with hidden, implied content and affect
Effect on the client: challenges client
Client relationship: additive to client's explicit expressions
Timing: used sparingly
Reflects the counselor's point of view
Pay attention to nonverbal cues, point out recurring themes, make connections, point
out alternatives, develop logical progression for the client
Advanced Empathy - ANSWER-Used to go below the surface of a conversation
Reflection of things not directly stated
Includes reframing and interpretation
Alagille Syndrome - ANSWER-syndromic, multi-system disorder
Cholestasis (bile duct paucity), CHD, butterfly vertebrae, growth restriction, RP changes
common
AD: JAG1, NOTCH2 - 50% de novo
rt (AR, XL): syndromic, multi-system disorder - ciliopathy
Molar tooth sign, hypotonia, DD, apnea, colobomas, polydactyly, endocrine anoms,
retinal dystrophy
Allelic heterogeneity - ANSWER-different mutations in the same gene can cause
similar/identical phenotype
Alpha-1-Antitrypsin deficiency - ANSWER-Autosomal codominant: SERPINA1 (AAT
protein)
1:1,500 - 3,500 European ancestry
Alleles: M (WT), S, Z - SZ and ZZ disease alleles
Clinical features: onset in 20-50s
Lung disease, COPD → emphysema
Liver disease, liver cirrhosis (liver transplant needed)
Treatment: lung and/or liver transplant, AAT therapy
Alpha-Thalassemia - ANSWER-AR: HBA1, HBA2 (deletions)
Two copies of each gene - four total
Decreased or absent hemoglobin A due to few/no production of α-globin chains
1:20 Asian carriers [cis]; 1:30 AA carrier [trans]
, Genotypes
α+ single gene deletion - asymptomatic/"silent"
α° 2 allele deletion - "trait" - smaller RBCs
HbH 3 allele deletion - microcytic anemia, hepatosplenomegaly
HbBart 4 allele deletion - most severe!
Severe IU hypoxia, fetal hydrops, neonatal death
General clinical features: anemia, splenomegaly, heart defects
DNA testing required for carriers - Hgb electrophoresis normal
Treatment: chronic infusions with chelation to remove excess iron
Alport Syndrome - ANSWER-XL (80%): COL4A5; AR, AD
Clinical features: progressive renal disease (ESRD), progressive SNHL, ocular
abnormalities
Alzheimer's disease - ANSWER-General lifetime risk: ~10-15%
Most common cause of dementia
~11% 65+ have AD; 2/3 women
Early onset: <55-60 y
AD: APP, PSEN1, PSEN2
Late onset: >65 y
Multifactorial/AD - heritability 60-80%
APOE: e4 is RISK FACTOR, e2 is protective
Clinical features:
Progressive degenerative disease → cortex shrivels up
Gradual memory loss, personality & behavioral changes, loss of language skills,
withdrawal
Characteristic neuropathy: plaques (Beta-amyloid), tangles (tau)
Amino acidopathies - ANSWER-inability to metabolize certain amino acids → buildup of
amino acids and/or by-products
PKU (phenylketonuria)
AR: PAH
1:12,000 Caucasians; carrier 1:50 - NBS
Phenylalanine cannot be converted to tyrosine → accumulates as phenylketones
Clinical features: normal development if treatment maintained
Normal for first few mos
If untreated: DD/ID, seizures, mousy odor, fair complexion, behavioral issues
Treatment: low protein diet, Kuvan (cofactor treatment)
Tyrosinemia I: AR - liver cirrhosis/failure, kidney failure, hypertensive crises, rickets -
cured by liver transplant
Homocystinuria: AR - Marfanoid habitus (arachynodactyly, pectus, scoliosis, retinal
detachment), still joints, ID
Cystinuria: AR - kidney stones
Amyotrophic lateral sclerosis - ANSWER-1-3/100,000
~90% sporadic, 10% familial
22q11.2 deletion syndrome (aka DiGeorge) - ANSWER-1:1-2000 - most common
microdeletion
2nd most common cause of CHD after DS
Contiguous gene deletion syndrome
AD deletion of 22q11.2 (~50 genes in this region)
10% familial mutations
Detected by: FISH, microarray, MLPA
Clinical features:
Endocrine: hypocalcemia, short stature, hyperparathyroidism
Cardiac: tetralogy of fallot, truncus arteriosus
Immunodeficiency: thymic atrophy
Palate: CL+/-P, velopharyngeal insufficiency
Psychiatric: schizophrenia, bipolar disorder, anxiety, depression
DD/ID, seizures, SNHL
GI/GU anomalies, malignancy (Wilms), skeletal issues (scoliosis)
ACE inhibitor - ANSWER-renal tubular acidosis → potter sequence, IUGR
Achondroplasia - ANSWER-~1/15-40,000
AD: FGFR3
~80% de novo; associated with APA
~98% 1138G>A
Homozygous mutations are lethal
Clinical features
Rhizomelic shortening, short stature, trident hands, brachydactyly, macrocephaly,
frontal bossing, mid-face hypoplasia, lumbar lordosis/kyphosis, genu varum, foramen
magnum stenosis, normal IQ
AD Polycystic Kidney Disease - ANSWER-Late onset bilateral renal cysts, cysts on
liver, seminal vesicles, pancreas, arachnoid membranes, intracranial aneurysm, dilation
of the aortic root, dissection of the thoracic aorta, mitral valve prolapse, abdominal wall
hernia
50% will have end stage renal disease by age 60
Unilateral enlarged kidney
Presenting symptom is flank pain, hematuria
US detection ~10% of the time
AD PKD1 (85%) PKD2 (15%)
1 in 1000
Adrenoleukodystrophy - ANSWER-XL: ABCD1 [pseudogenes]
1:20-50,000 males; female carriers can have neurological symptoms
Toxic build-up of VLCFAs
Most affected tissues: myelin, adrenal cortex, leydig cells of testes
Three clinical forms:
,Addison's: onset child-adult - only adrenal insufficiency, fertility issues
Adrenomyeloneuropathy: onset 20-30s - progressive stiffness/weakness, some adrenal
insufficiency
Cerebral form: onset child-adolescence - rapidly progressive, severe cognitive &
neurologic disability, impaired adrenal function, die within 2-5 y of diagnosis
Treatment: Lorenzo's oil, HSCT in early patients, diet w/o VLCFAs, HRT
advanced empathy - ANSWER-Purpose: counselor response goes beyond what the
client expresses and goes into inner thoughts and feelings, usually occurs late in a
session
Content level: deals with hidden, implied content and affect
Effect on the client: challenges client
Client relationship: additive to client's explicit expressions
Timing: used sparingly
Reflects the counselor's point of view
Pay attention to nonverbal cues, point out recurring themes, make connections, point
out alternatives, develop logical progression for the client
Advanced Empathy - ANSWER-Used to go below the surface of a conversation
Reflection of things not directly stated
Includes reframing and interpretation
Alagille Syndrome - ANSWER-syndromic, multi-system disorder
Cholestasis (bile duct paucity), CHD, butterfly vertebrae, growth restriction, RP changes
common
AD: JAG1, NOTCH2 - 50% de novo
rt (AR, XL): syndromic, multi-system disorder - ciliopathy
Molar tooth sign, hypotonia, DD, apnea, colobomas, polydactyly, endocrine anoms,
retinal dystrophy
Allelic heterogeneity - ANSWER-different mutations in the same gene can cause
similar/identical phenotype
Alpha-1-Antitrypsin deficiency - ANSWER-Autosomal codominant: SERPINA1 (AAT
protein)
1:1,500 - 3,500 European ancestry
Alleles: M (WT), S, Z - SZ and ZZ disease alleles
Clinical features: onset in 20-50s
Lung disease, COPD → emphysema
Liver disease, liver cirrhosis (liver transplant needed)
Treatment: lung and/or liver transplant, AAT therapy
Alpha-Thalassemia - ANSWER-AR: HBA1, HBA2 (deletions)
Two copies of each gene - four total
Decreased or absent hemoglobin A due to few/no production of α-globin chains
1:20 Asian carriers [cis]; 1:30 AA carrier [trans]
, Genotypes
α+ single gene deletion - asymptomatic/"silent"
α° 2 allele deletion - "trait" - smaller RBCs
HbH 3 allele deletion - microcytic anemia, hepatosplenomegaly
HbBart 4 allele deletion - most severe!
Severe IU hypoxia, fetal hydrops, neonatal death
General clinical features: anemia, splenomegaly, heart defects
DNA testing required for carriers - Hgb electrophoresis normal
Treatment: chronic infusions with chelation to remove excess iron
Alport Syndrome - ANSWER-XL (80%): COL4A5; AR, AD
Clinical features: progressive renal disease (ESRD), progressive SNHL, ocular
abnormalities
Alzheimer's disease - ANSWER-General lifetime risk: ~10-15%
Most common cause of dementia
~11% 65+ have AD; 2/3 women
Early onset: <55-60 y
AD: APP, PSEN1, PSEN2
Late onset: >65 y
Multifactorial/AD - heritability 60-80%
APOE: e4 is RISK FACTOR, e2 is protective
Clinical features:
Progressive degenerative disease → cortex shrivels up
Gradual memory loss, personality & behavioral changes, loss of language skills,
withdrawal
Characteristic neuropathy: plaques (Beta-amyloid), tangles (tau)
Amino acidopathies - ANSWER-inability to metabolize certain amino acids → buildup of
amino acids and/or by-products
PKU (phenylketonuria)
AR: PAH
1:12,000 Caucasians; carrier 1:50 - NBS
Phenylalanine cannot be converted to tyrosine → accumulates as phenylketones
Clinical features: normal development if treatment maintained
Normal for first few mos
If untreated: DD/ID, seizures, mousy odor, fair complexion, behavioral issues
Treatment: low protein diet, Kuvan (cofactor treatment)
Tyrosinemia I: AR - liver cirrhosis/failure, kidney failure, hypertensive crises, rickets -
cured by liver transplant
Homocystinuria: AR - Marfanoid habitus (arachynodactyly, pectus, scoliosis, retinal
detachment), still joints, ID
Cystinuria: AR - kidney stones
Amyotrophic lateral sclerosis - ANSWER-1-3/100,000
~90% sporadic, 10% familial
