Monogenetic Non-diabetic Endocrine Syndromes Flashcards
what does MEN stand for
multiple endocrine neoplasia
inheritance seen in MEN1
autosomal dominant
where do MEN1 mutations occur
MEN1 gene located on chromosome 11q13
what is the typical result of mutations associated with MEN1
loss/reduced protein function
what are MEN1 genes involved in (3)
how a cell responds to DNA damage, chromatin remodelling and cell signalling pathway regulation
how do patients with MEN1 usually present
pituitary adenoma
leading cause of excess deaths in MEN1
malignant pancreatic neuroendocrine tumour and thymic carcinoids
what are the indications for germline MEN1 testing
2+ MEN1 associated tumours or familial diagnosis
clinical suspicion
first degree relative with diagnosis
what is the goal of management of MEN1
prevent premature morbidity and mortality from MEN1-associated tumours, while preserving quality of life
what causes MEN2
Autosomal dominant RET gene mutation
what are the 2 main subtypes of MEN2
a and b
what is another name for MEN2a
sipple syndrome
what is the most common subtype of MEN2
a
what is sipple syndrome
the combination of medullary thyroid cancer in association with phaeochromocytoma and parathyroid tumours
what is MEN2b
MTC and pheochromocytoma in association with a marfanoid habitus, mucosal neuromas, medullated corneal fibres, intestinal autonomic ganglion dysfunction
what is the typical first manifestation of MEN2
medullary thyroid cancer
what is von hippel-lindau syndrome
Inherited disorder causing multiple tumours (both benign and malignant) in the central nervous system (CNS) and viscera
what inhertance is seen in von hippel-lindau syndrome
autosomal dominant
pathophysiology of VHL
mutation in VHL gene leads to accumulation of HIF proteins and stimulation of cellular proliferation
what is neurofibromatosis type 1
genetic condition that causes tumours along the nervous system
what causes neurofibromatosis type 1
mutation in the NF1 gene
diagnostic criteria for neurofibromatosis type 1
2 or more of the following:
cafe au lait macules
>2 neurofibromas
axillary or inguinal freckling
optic glioma
lisch nodules
first degree relative with NF1
name some other features of NF1
scoliosis, learning difficulties and rarely phaeochromocytoma
what causes carney complex
Mutation in PRKAR1A
what is characteristic of carney complex
by multiple benign tumours most often affecting the heart, skin and endocrine system and abnormalities in skin pigmentation
what is McCune-Albright syndrome
complex genetic disorder affecting the bone, skin and endocrine systems
what causes McCune-Albright syndrome
Post-zygotic somatic GNAS mutation
clinical presentation of McCune-Albright syndrome
cafe au lait skin pigmentation
precocious puberty
thyroid nodules
cushings syndrome
