04 - Genetic disorders Flashcards
One dominant allele is enough to produce phenotype (heterozygous); diseases with mutations in key structural proteins/receptors are usually inherited in this manner; examples: Huntington disease, NF, Myotonic dystrophy, TSC, ADPKD, Familial polyposis coli, HS, vWD, Marfan syndrome, EDS (some types), OI, Achondroplasia, Familial hypercholesterolemia, AIP
Autosomal dominant
Two recessive alleles produce phenotype; enzyme deficiencies are usually inherited in this manner: examples: CF, PKU, Galactosemia, Homocystinuria, Lysosomal storage diseases, a-1-antitrypsin deficiency, Wilson disease, Hemochromatosis, Glycogen storage diseases, SCA, Thalassemias, CAH, EDS (some types), Alkaptonuria, Neurogenic muscular atrophies, Freidrich ataxia, Spinal muscular atrophy
Autosomal recessive
Most common lysosomal storage disorder; most common form is chronic, non-neuronopathic form (Type I); acute neuronopathic form (Type II) most severe; microscopically, distended phagocytic cells in spleen, liver, BM, LNs, tonsils, thymus and Peyer patches, with fibrillary cytoplasm crumpled tissue paper appearance).
Gaucher disease
In this pattern of inheritance, females in general are more affected than males (in any scenario), because one allele in a female is enough to manifest the trait; examples: Alport syndrome and Vitamin D-resistant rickets
X-linked dominant disorders
Most common of the chromosomal disorders; leading cause of MR; most common cause: nondisjunction of Ch21 during meiosis; diagnostic clinical features: flat facial profile, oblique palpebral fissures, and epicanthal folds.
Trisomy 21 (Down syndrome)
Prominent occiput, mental retardation, micrognathia, low-set ears, short neck, overlapping fingers, CHDs, renal malformations, limited hip abduction, and rocker-bottom feet are features of this syndrome.
Trisomy 18 (Edward syndrome)
In this pattern of inheritance, males are usually affected due to hemizygosity of the allele, but females may express phenotype due to random activation of one X chromosome; examples: DMD, Hemophilia A and B, CGD, G6PD deficiency, Agammaglobulinemia, Wiskott-Aldrich syndrome, DI, Lesch-Nyhan syndrome, Fragile X syndrome
X-linked recessive disorders
Microcephaly and mental retardation, microphathalmia, polydactyly, cardiac defects, umbilical hernias, renal defects, and rocker-bottom feet are features of this syndrome.
Trisomy 13 (Patau syndrome)
Components of Chromosome 22q11.2 deletion syndrome.
DiGeorge syndrome (CATCH22) and velocardiofacial syndrome
Patients with Ch22q11.2 deletion syndrome are at high risk of these disorders.
Schizophrenia and bipolar disorders
Condition characterized by 2X chromosomes and 1Y chromosomes; most common karyotype is 47XXY (90%); important cause of reduced spermatogenesis and male infertility; clinical features include: eunuchoid body habitus, testicular atrophy, micropenis, absence of secondary sex characteristics, etc.
Klinefelter syndrome
Complete or partial monosomy of X chromosome; female hypogonadism in phenotypic females; Most common abnormality is lack of entire X chromosome (45XO) (57%); single most important cause of primary amenorrhea; clinical features include: ovarian streaks, absence of secondary sex characteristics, short stature, cystic hygromas of head neck, preductal CoA, etc.
Turner syndrome
Type of hermaphrodism with presence of both ovarian and testicular tissue.
True hermaphrodism
Type of hermaphrodism characterized by disagreement between phenotypic and gonadal sex; examples: MRKH syndrome and androgenital syndromes
Pseudohermaphrodism
Property of trinucleotide repeat disorders wherein the disease worsens with each successive generation.
Anticipation
