Part 1 Flashcards
(23 cards)
Connatal malformation
Deformation: pes equinovarus
Disruption: torticollis (wry neck, ngheo co)
Deformation sequence: arthgryposis multiplex congenita (AMC) characteristic by multiple joint contracture, muscle weakness and fibrosis
Disruption sequence: ADAM syndrome
Minor abnormalies
simian crease, preauricular tag/fistula, supernumerary nipples
Definition of congenital malformation
Physical defect present in a baby at birth (genetic or prenatal event)
Development of a structure is arrested and misdirected, delayed and the effect is permanent
Social significance of congenital malformation
Leading cause of infant mortality in US and many developed contries
1/3 babies in US
Reduced penetrance
Abnormal gene is present but it does not manifest it self in the phenotype
Some people with the mutation but do not develop disorder’s feature
Variable of expressivity
Range of signs and symptoms that occur in different people with the same genetic condition
Exp: marfan syndrome
Apert syndrome
Dominant disorder Chromosome 10 FGFR2 mutation Features: Clover shape head Mild/moderate/severe mental retardation Limb disturbance (syndactyly) Congenital heart defect
Achondroplasia
Dominant mutation Chromosome 4p 1138 Arg-Gly FGFR3 mutation Features: Bone, connective tissue, muscle are involved Low muscle tone (hypotonity) Slow motor movement Abnormal skull structure
Codominance
A phenomenone in which a single gene has more than one dominant allele
Express the phenotype associated with both alleles
Exp: blood group
Marfan syndrome
Autosomal dominant, variable expressity Chromosome 15 (15q15-q21.3) Fibrillin-1 mutation (component of elastin)-> weaker elastin Incidence: 1/10000 Features: Pectus exavatum, carinatum Scoliosis Ectopia lentis Dilatation of the aorta, aortic dissection
Mitochondrial gene
Single chain, circular, called mDNA, 37 genes, code for ATP producing metabolic pathway
High mutation rate but no repair mechanism
Variable expressity
Maternal inheritance
Mitochondrial inheritance diseases
Hereditary opticus neuropathy
MERF (myoclonic epilepsy-Ragged red fiber)
Kaerms Sayre syndrome
MELAS (mitochondrial enceloparhy lactase acidosis stroke like episode)
Hereditary opticus neuropathy
Leber disease
Point mutation: 11778 position of ND4 gene
Maternal inheritance
Visual loss, neurological symptoms
MERF (myoclonic epilepsy Ragged red fiber)
Point mutation in Lys gene of tRNA
Sporadic/maternal inherit
Myo epilepsy, neurological symptoms, ataxia, dementia, myopathy due to Ragged red fiber in muscle
Kaerms-Sayre syndrome
Mitochondrial inheritance disease
Big tandem mutation, big deletion
Sporadic inherit
AV block, cerebellar damage, retinopathy, external opthalmogia, deafness, hypotone
MELAS (mitochondrial encelopathy lactate acidosis stroke like episode)
Mitochondrial inheritance disease Point mutation in Leu gene of tRNA Sporadic/maternal Severe hypotone Nygstamus Encelopathy Behavioral diaturbance
Fragile X syndrome
Triple expansion CGG triplet in the 5’ non translated region of FMR 1 gene (fragile mental retard)
Chromosome X q27.3
1:1000-4000 male
1:2000-6000 female (1/259 fm carrier)
29-50 healthy
52-200 unstable
>200 gene methylation-> loss of gene function (folic acid)
No neuron maturation
Features: mental retardation, autism, delay of speaking, big head long face, hyperactive
Triplet expansion related disease
Fragile X syndrome CGG Xq27.3 FMR1 FRAX E CGG Xq28 FRA-F Hungtinton Chorea: CAG, 4p16.3 Spinobulbar muscular atrophy
Down syndrome
Trisomy Critical segment 21q22 Critical region 21q22.1 Features Short neck, small ear, straight hair, upward slanting of eyes, small mouth of large tongue, flat face Various degree of mental retardation Congenital heart disease Risk of leukemia Early onset of Alzheimer, dementia
Cytogenetics of Down syndrome
47, XX/XY +21 (95%)
46, XY, rob(21,22) +21
45 XX, -21,-22 t(21,22)
46, XY, -13,-14, t(13,14), +21
Down syndrome related genes
Gout gene: purine synthesis, mental retardard
CRYA1 gene: crystalline-> disturbance of lens
APP and AD1 gene: Alzheimer’s gene
Hemophilia
X linked recessive disease
Spontaneous mutation
Xq 26-28
A factor VIII (33%), B factor IX 20%
Dunchenne muscular dystrophy
X link recessive disease
Dystrophin gene Xq21.2 delete mutation
Dystrophyn is intracellular protein in 2 transmembrane complex (dystroglycan- sacroglycan)
Variable expressity
Features:
Muscle weakness
Walking on tip toe, difficult climbing the stare
Standing up from crouching
Gover’s symptoms: patients have to use their arm to walk up due to weakness of hip and thigh muscle
Cardiomyopathy
