Genetic Disorders Flashcards
Cystic Fibrosis
Mutation, Complication, Unique Characteristic
Autosomal recessive Cystic fibrosis transmembrane conductance regulator gene defect
Defective epithelial chloride channel causing abnormally viscous secretions
Heterozygotes still present with higher rates of respiratory and pancreatic disease
Cystic Fibrosis
Presentation (8)
Chronic lung disease (bronchopneumonia) recurrent infections (influenzae and aeruginosa) pancreatic insufficiency steatorrhea malnutrition hepatic cirrhosis intestinal obstruction (meconium ileus) male infertility (malformation)
Phenylketonuria
Mutation and Presentation (4)
Autosomal recessive phenylalanine hydroxylase deficiency
Presents with hypopigmentation, musty urine odor, mental retardation, eczema
Marfan Syndrome
Mutation, Pathogenesis, Presentation
Autosomal dominant loss of function defect in chromosome 15 FBN1 gene
Causes loss of microfibril structural support and excessive TGF-beta signaling
Presents with tall, long extremities/fingers, hypermobile joints, ectopia lentis, death via aortic dissection
Ehlers-Danlos (Classic, Vascular and Kyphoscoliosis) Associated Mutation and Presentation
Classic: COL5A1/COL5A2 mutation
Skin/Joint hypermobility, atrophic scars, easy bruising
Vascular: COL3A1 mutation
Thin skin, arterial/uterine rupture, bruising joint hyperextensibility
Kyphoscoliosis: Lysyl hydroxylase
Hypotonia, joint laxity, congenital scoliosis, ocular fragility
Familial Hypercholesterolemia
Mutation and Presentation (3)
Autosomal dominant loss of function defect in LDL receptor leading to increase in serum cholesterol
Presents with xanthomas, premature atherosclerosis, premature myocardial infarction (age 20)
Familial Hypercholesterolemia
Classes (I-V) and Descriptions
Class I: no receptor synthesis
Class II: no receptor transport, build up in ER
Class III: on cell, don’t bind LDL
Class IV: bind LDL but don’t internalize it
Class V: receptor can’t dissociate from LDL, no recycling occurs
Tay Sachs Disease
Mutation, Presentation (6), Morphology (3), Risky Population
Hexosaminidase A deficiency from chromosome 15 mutation leading to GM2 ganglioside buildup
Presentation: normal at birth then motor and mental deterioration, obtunded, flaccid, blind, dementia
Morphology: cherry red macula with ballooned neurons and build up in retina
High risk in Ashkenazic Jews
Niemann-Pick Disease
Mutation, Presentation (A,B,C), Morphology, Risky Population
Autosomal recessive Sphingomyelinase deficiency from Chomosome 11 mutation
A: severe infantile, neuro issues and visceral sphingomyelin, death by age 3
B: no CNS involved, reach adult
C: NPC1 defect, progressive neurological damage and gait ataxia
Large cells with foamy cytoplasm and zebra bodies, some have cherry red spot in macula
High risk in Ashkenazic Jews
Gaucher Disease
Mutation, Presentation (I, II, III), Morphology
Autosomal recessive Glucocerebrosidase mutation causing gluceroside to activate phagocytes
I: No CNS involvement (90% Ashkenazic)
II: infantile cerebral pattern with early death and hepatosplenomegaly (not Jews)
III: systemic symptoms with progressive CNS issues
Distended phagocytes (Gaucher cells) in liver, spleen and bone marrow with crumpled tissue paper cytoplasm, pancytopenia
Mucopolysaccharidoses
Defect, Presentation (Hunter/Hurler), Morphology
Alpha L-Iduronidase deficiency (Hurler)
L-Iduronosulfate sulfatase deficiency (Hunter)
Hurler: corneal clouding, cardio issues, coarse face, hepatosplenomegaly, death by 6-10 years via MI
Hunter: no clouding, X linked defect
Ballooned cells that are PAS+ with Lamellated Zebra Bodies
Von Gierke Disease
Mutation, Presentation (5), Morphology
Glucose 6-Phosphatase deficiency
Failure to thrive, hypoglycemia, hyperlipidemia, xanthomas, bleeding
Hepatomegaly, Renomegaly via intracytoplasmic glycogen
Pompe Disease
Mutation, Presentation (3), Morphology (3)
Acid maltase deficiency
Hypotonia, cardiorespiratory failure, chronic myopathy
Mild hepatomegaly, cardiomegaly, skeletal muscle swelling
Down’s Syndrome
Karyotypes, Incidence, Presentation (4), Associated Disorders (4)
47 chromosomes via trisomy 21
46 chromosomes via translocation
46 or 47 chromosomes via mosaicism
1 in 700 incidence, 95% have trisomy 21
flat facial profile, oblique palpebral fissures, epicanthic folds, intestinal stenosis
Congenital heart disease, acute leukemia, alzheimers, immune deficiency
Patau Syndrome (trisomy 13) Clinical Features (4)
Cleft lip and palate
Cardiac and renal defects
Polydactyly
Microcephaly
Edwards Syndrome (trisomy 18) Clinical Features (5)
Micrognathia Prominent occiput Low set ears Short neck Overlapping fingers
DiGeorge Syndrome
Chromosomal Anomaly and Presentation (4)
Deletion of band q11.2 on chromosome 22
Thymic and Parathyroid hypoplasia, hypocalcemia and cardiac malformations
Velocardial Facial Syndrome
Chromosomal Anomaly and Presentation (4)
Deletion of band q11.2 on chromosome 22
prominent nose, retrognathia, cleft palate, learning disabilities
Klinefelter Syndrome
Incidence, Karyotype, Presentation (4), Associated Disorders (5)
1 in 660 live males
47 XXY karyotype
long legs, small genitalia, gynecomastia, low IQ
Type 2 Diabetes, Mitral valve prolapse, osteoporosis, breast cancer and infertility
Turner Syndrome
Karyotype, Presentation (6), Associated Disorders (4)
45 X karyotype or mosaicism
Short, webbed neck, broad chest with wide nipples, amenorrhea, streak ovaries, obesity
Hypothyroidism, congenital heart disease, Glucose intolerance, Insulin resistance
Prader Willi Syndrome
Mutation and Presentation (7)
Paternal chromosome 15 deletion
Mental retardation, short stature, hypotonia, hyperphagia, obesity, small hands and feet, and hypogonadism
Angelman Syndrome
Mutation and Presentation
Maternal chromosome 15 deletion
Ataxia, mental retardation, seizures, happiness
Fragile X Syndrome
Mutation and Presentation (4)
CGG repeat on Familial mental retardation 1 gene mutation on X chromosome
Causes loss of function of FMR1 protein
Presents with large mandible/ears/testicles and mental retardation
Huntington’s Disease
Mutation and Presentation
Autosomal dominant polyglutamine trinucleuotide repeat expansion of HTT gene
Causes toxic gain of function of huntingtin protein
Progressive movement disorder and dementia from striatal neuron loss
Glucose 6 Dehydrogenase Deficiency
Disorder Type and Clinical Manifestation
X linked recessive disorder, mostly in men
Causes drug induced red cell hemolysis
Fragile X Tremor Ataxia
Mutation and Presentation (2)
CGG trinucleotide repeat on FMR1 gene
Causes toxic gain of function in FRM1 protein
Causes intention tremor and cerebellar ataxia
