Genetic disorders and Neoplasia Flashcards
Autosomal dominant and recessive diseases have opposing features of age of onset, which one is which?
Dominant-Occurs later in life usually
Which disorders are dominant?
BAMN
Brugada, Achondroplasia, Marfan syndrome, and Neurofibromatosis
What is Brugada Syndrome due to?
Due to defect in gene that codes for Na, K, or Ca channels in the heart
What is often the first symptom of someone who has Brugadas?
Sudden cardiac death with structurally normal hearts
What causes development of Achondroplasia?
A mutation in the gene for FGF receptor 3
80% of individuals with achodroplasia have parents of average height, meaning most cases result from ___ mutations.
De novo
What is the paternal age effect?
New, sporadic dominant mutations occurring with advanced paternal age.
Over the age of 40 has an increase risk of passing on a mendelian condition, primarily autosomal dominant ones that were not present in either parent
What causes Marfan syndrome?
Dysfunction in a gene that codes for fibrillin 1 needed for production of elastic fibers
What are the pleiotropic effects observed in Marfans syndrome?
Disproportionately tall stature, ocular changes, sever myopia, retinal detachments, dislocations of the lenses, hyperextensible skin, bruising easily, poor wound healing
Most serious is dilation of the aortic root, leading to rupture and sudden death
What is the genetic defect in Neurofibromatosis?
Defect in a tumor suppressor gene involved in cell division and growth, causing tumor formation by Schwann cells
What are the two neurofibromatosis and their manifestations?
NF-1- learning disabilities, ADD, speech abnormalities
NF-2- Absence or minimal cutaneous lesions, progressive deafness and bilateral acoustic neuromas
What do autosomal recessive mutations often lead to?
Loss of enzyme function (inborn errors of metabolism)
What are the two characteristics of autosomal recessive disorders that distinguish it from a dominant disorder?
AR results in early onset of disease and uniform symptomology
What are the four autosomal recessive disorders we discuss?
PaTT
Phenyketonuria, Tay Sachs disease, A1 antitrypsin deficiency, Thalassemias
What is the genetic defect in phenylketonuria?
Most commonly lack of phenyalanine hydroxylase, which converts phenyalanine to tyrosine. Excess Phenylalanine is toxic to the brain
What are manifestations of PKU? If left untreated?
Mental retardation, microcephaly, seizures, decrease pigmentation
Post natal growth restrictions, intellectual disability, recurrent seizures
What deficiency causes Tay Sachs Disease?
Hexominidase A, which breaks down GM2 ganglioside
It ends up accumulating in the lysosomes in this disease when not broken down
What are the manifestations of Tay Sachs Disease?
Weakness, muscle flaccidity, decreased attentivenessk blindness
What does the progression of Tay Sachs Disease look like?
Normal at birth, symptoms at 3-6 months, death at 4-5
What does alpha 1 antitrypsin deficiency cause?
Alveolar damage due to increased elastic fiber destruction and emphysema
What can also cause similar symptoms as a1 antitrypsin disease?
Smoking
What does Thalassemias result from?
Mutations causing deficient synthesis of alpha or beta globin chain of hemoglobin and compensation by increasing the unaffected chain
What does alpha thalassemias cause?
Doesnt really say, but its not as bad as Beta thalassemia
What does beta thalassemia cause?
Heinz bodies produced r/t increase alpha chains. The heinz bodies damage the cell and cause lysis
