Endocrine and Genetic Syndromes

Gene/chromosome: MEN1, chromosome 11; Inheritance: Autosomal dominant; Triad: Parathyroid, pancreatic/duodenal NET, pituitary tumors; Associated: Gastrinoma, insulinoma, prolactinoma; Investigation: MEN1 testing, calcium/PTH, hormone evaluation

Gene/chromosome: RET, chromosome 10; Inheritance: Autosomal dominant; Triad: Medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism; Associated: Medullary thyroid carcinoma; Investigation: RET testing, serum calcitonin, metanephrines

Gene/chromosome: RET, chromosome 10; Inheritance: Autosomal dominant; Triad: Medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas; Associated: Marfanoid habitus, intestinal ganglioneuromatosis; Investigation: RET testing, serum calcitonin

Gene/chromosome: PRKAR1A, chromosome 17; Inheritance: Autosomal dominant; Triad: Spotty pigmentation, cardiac myxomas, endocrine overactivity; Associated: Primary pigmented nodular adrenal disease, pituitary adenoma; Investigation: PRKAR1A testing, echocardiography

Gene/chromosome: GNAS, chromosome 20; Inheritance: Somatic mosaicism; Triad: Café-au-lait spots, polyostotic fibrous dysplasia, precocious puberty; Associated: Thyroid and other endocrine hyperfunction; Investigation: Clinical diagnosis, skeletal imaging, endocrine evaluation

Gene/chromosome: ANOS1 and other genes; Inheritance: Often X-linked or autosomal; Triad: Hypogonadotropic hypogonadism, anosmia, delayed puberty; Associated: Infertility, renal agenesis in some forms; Investigation: Low GnRH-dependent gonadotropins, MRI olfactory bulbs

Gene/chromosome: 47,XXY; Inheritance: Usually sporadic; Triad: Tall stature, small testes, infertility; Associated: Gynecomastia, osteoporosis, increased breast cancer risk; Investigation: Karyotyping, elevated FSH/LH with low testosterone

Gene/chromosome: 45,X or mosaic; Inheritance: Usually sporadic; Triad: Short stature, webbed neck, streak ovaries; Associated: Coarctation of aorta, bicuspid aortic valve, horseshoe kidney; Investigation: Karyotype, echocardiography

Gene/chromosome: CYP21A2, chromosome 6; Inheritance: Autosomal recessive; Triad: Virilization, salt wasting, adrenal insufficiency; Associated: Ambiguous genitalia in XX infants, neonatal crisis; Investigation: Increased 17-hydroxyprogesterone

Gene/chromosome: AR, chromosome X; Inheritance: X-linked; Triad: 46,XY, female external phenotype, absent uterus; Associated: Undescended testes, inguinal hernia; Investigation: Karyotype, testosterone, AMH, AR testing

Gene/chromosome: 15q11-q13 paternal deletion or maternal uniparental disomy; Inheritance: Imprinting disorder; Triad: Neonatal hypotonia, hyperphagia, hypogonadism; Associated: Obesity, diabetes, sleep apnea; Investigation: DNA methylation analysis

Gene/chromosome: 15q11-q13 maternal deletion or UBE3A defect; Inheritance: Imprinting disorder; Triad: Severe developmental delay, ataxia, inappropriate laughter; Associated: Seizures, microcephaly; Investigation: DNA methylation analysis

Gene/chromosome: Multiple BBS genes; Inheritance: Autosomal recessive; Triad: Retinal dystrophy, obesity, polydactyly; Associated: Renal abnormalities, hypogonadism; Investigation: Fundoscopy/ERG, renal evaluation, genetic testing

Gene/chromosome: COL4A5 X-linked; COL4A3/COL4A4 autosomal; Inheritance: X-linked or autosomal recessive/dominant; Triad: Hematuria, sensorineural hearing loss, ocular abnormalities; Associated: Progressive CKD, lenticonus; Investigation: Kidney biopsy showing GBM changes, collagen IV testing

Gene/chromosome: PKD1 chromosome 16, PKD2 chromosome 4; Inheritance: Autosomal dominant; Triad: Bilateral renal cysts, hypertension, flank pain; Associated: Intracranial berry aneurysm, hepatic cysts, mitral valve prolapse; Investigation: Renal ultrasound, genetic testing when indicated

Gene/chromosome: PKHD1, chromosome 6; Inheritance: Autosomal recessive; Triad: Enlarged kidneys, congenital hepatic fibrosis, portal hypertension; Associated: Caroli disease, neonatal respiratory compromise; Investigation: Prenatal/neonatal renal ultrasound, liver evaluation

Gene/chromosome: SCNN1B or SCNN1G; Inheritance: Autosomal dominant; Triad: Early hypertension, hypokalemia, metabolic alkalosis; Associated: Low renin, low aldosterone; Investigation: Electrolytes, renin/aldosterone, genetic testing

Gene/chromosome: SLC12A3, chromosome 16; Inheritance: Autosomal recessive; Triad: Hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria; Associated: Low blood pressure, muscle cramps; Investigation: Serum electrolytes, urinary calcium, genetic testing

Gene/chromosome: SLC12A1, KCNJ1, CLCNKB and others; Inheritance: Usually autosomal recessive; Triad: Hypokalemic metabolic alkalosis, hyperreninemia, hyperaldosteronism; Associated: Normal/low BP, hypercalciuria in classic forms; Investigation: Electrolytes, urinary calcium, genetic testing

Gene/chromosome: Multiple causes; Inheritance: Acquired or inherited; Triad: Glycosuria, phosphaturia, aminoaciduria; Associated: Proximal renal tubular acidosis, rickets/osteomalacia; Investigation: Urinalysis, serum phosphateicarbonate, urine amino acids

Gene/chromosome: AVPR2 X-linked, AQP2 autosomal; Inheritance: X-linked or autosomal; Triad: Polyuria, polydipsia, inability to concentrate urine; Associated: Hypernatremia, dehydration; Investigation: Water deprivation/desmopressin testing under supervision, urine osmolality