SM_193b: Endocrine Genetic Syndromes Flashcards
(46 cards)
Describe the timing of manifestation of genetic disorders
Timing of manifestation of genetic disorders
- Chromosomal
- Monogenic
- Polygenic / multifactorial
Complex disorders are influenced by ___, ___, and ___
Complex disorders are influenced by susceptibility genes, environment / lifestyle, and mutliple genes / factors
Monogenic diabetes is a ___
Monogenic diabetes is a single gene defect (autosomal dominant) leading to development of diabetes mellitus
- Often misdiagnosed as T2DM
- Lack of diabetes autoantibodies
T2DM is caused by ___
T2DM is caused by a complex interaction of multiple genes and environmental factors
- Large genetic basis: some SNPs
- Diet and obesity: lead to peripheral resistance to insulin-mediated glucose uptake and decreased sensitivity of beta cells to glucose, lifestyle modifications in diet and exercise improve insulin sensitivity
____ is the most common cause of male hypogonadism
Klinefelter’s Syndrome is the most common cause of male hypogonadism
Klinefelter’s Syndrome most often has the genotype ____
Klinefelter’s Syndrome most often has the genotype 47 XXY
- Due to nondisjunction of sex chromosomes
- Can be mosaic
Klinefelter’s Syndrome presents with ____, ____, ____, ____, ____, and ____
Klinefelter’s Syndrome presents with
- Increased length of arms and legs
- Gynecomastia
- Psychosocial abnormality
- Inattention
- Impairment of linguistic function
- Small firm testes with low sperm count and infertility
Turner syndrome most often has the genotype ___
Turner syndrome most often has the genotype 45 XO
- May have partial monosomy
- May be mosaic genotype
Describe presentation of Turner Syndrome
Turner Syndrome
- Lack of second X chromosome
- Small ovaries with few or no follicles, streak gonads leading to infertility
- Short stature
- Swelling of hands and feet
- Shield chest
- Low set hairline
- Heart disease
- Horseshoe kidney
- Ear infections and hearing loss
- ADHD
- Non-verbal learning disability
Congenital adrenal hyperplasia is ___
Congenital adrenal hyperplasia is a group of recessive disorders which causes a deficiency of an enzyme involved in the synthesis of cortisol, aldosterone, or both
- Classical CAH: 67% are salt losing, 33% are simple virilizing
Congenital adrenal hyperplasia results from mutations in ___
Congenital adrenal hyperplasia results from mutations in steroid synthesis pathway
___ is the most common form of congenital adrenal hyperplasia
21-hydroxylase deficiency is the most common form of congenital adrenal hyperplasia
- Prevents downstream formation of Androstenedione
- Chromosome 6p21, allows recombination during meiosis, unequal crossover events
Describe mutations causing congenital adrenal hyperplasia
Mutations causing congenital adrenal hyperplasia
Males with classic virilizing CAH present at ____ with ____, ____, ____, ____, ____, and ____
Males with classic virilizing CAH present at age 1-4 with failure to thrive, vomiting, dehydration, hypotension, hyponatremia, hyperkalemia, and shock
Females with classic virilizing congenital adrenal hyperplasia present with ____
Females with classic virilizing congenital adrenal hyperplasia present with ambiguous genitalia at birth due to excess androgens in utero
Describe tumor syndromes
Tumor syndromes
- Multiple Endocrine Neoplasia
- Pheochromocytoma / paraganglioma syndromes
- Von Hippel Lindau
- NF-1
- Li Fraumeni
- Carney Complex
Multiple Endocrine Neoplasia 1 affects the ____, ____, and ____
Multiple Endocrine Neoplasia 1 affects the parathyroid, pancreas, and pituitary
(3 P’s)
MEN1 presents with ____, ____, and ____
MEN1 presents with primary hyperparathyroidism, pituitary adenoma, and pancreatic / duodenal tumors
- Primary hyperparathyroidism: most common manifestation, presents in 2nd-4th decade of life, generally needs treatment with 3.5 gland resection
- Pituitary adenoma: prolactinoma is most common
- Pancreatic / duodenal tumors: gastrinoma is most common
MEN1 occurs due to ___
MEN1 occurs due to mutation in MEN1 gene that codes for the protein menin
- Knudsen’s two hit hypothesis: affected individuals inherit 1 mutation from a parent in autosomal dominant transmission, receive second hit leading to tumor formation
MEN 2A presents with ___, ___, and ___
MEN 2A presents with medullary thyroid cancer, primary hyperparathyroidism, and pheochromocytoma
- Hirschprung’s disease
- Cutaneous lichen amyloidosis
MEN 2B presents with ____, ____, and ____
MEN 2B presents with medullary thyroid carcinoma, pheochromocytoma, and intestinal ganglioneuromatosis
Medullary thyroid carcinoma is ____ that occurs commonly in patients with ____
Medullary thyroid carcinoma is a neuroendocrine tumor of the parafollicular or C-cells of the thyroid gland that occurs commonly in patients with MEN 2
- MEN 2A: incidence peaks in 3rd decade of life
- MEN 2B: occurs earlier and is more aggressive
- Early thyroidectomy is important
____ mutation can cause medullary thyroid carcinoma
Somatic RET mutation can cause medullary thyroid carcinoma
- Most is sporadic
Describe genetics of MEN 2
MEN 2 genetics
- Autosomal dominant gain of function mutation of RET proto-oncogene
- Germline mutation in the extracellular domain: MEN2A/FMTC
- Germline mutation: FMTC
- Germline mutation: TK2 domain (MEN 2B)
- Strong phenotype-genotype correlation
