Genetics

Genetics covers inherited and de novo disorders caused by chromosomal abnormalities, single-gene mutations, and mitochondrial DNA defects.

• Achondroplasia (FGFR3 gain-of-function, most common skeletal dysplasia, rhizomelic short stature, foramen magnum stenosis, vosoritide)
• Angelman Syndrome (chromosome 15 maternal deletion, happy puppet syndrome, seizures, severe intellectual disability)
• DiGeorge Syndrome (22q11.2 Deletion) (conotruncal heart defects, hypocalcemia, T-cell immunodeficiency, palatal anomalies)
• Down Syndrome (Trisomy 21) (intellectual disability, characteristic facies, heart defects, Alzheimer's risk)
• Ehlers-Danlos Syndrome (connective tissue disorder, hypermobility, skin fragility, vascular EDS)
• Fabry Disease (X-linked lysosomal storage, alpha-galactosidase A deficiency, neuropathic pain, enzyme replacement)
• Familial Mediterranean Fever (MEFV gene, periodic fever, serositis, amyloidosis, colchicine)
• Fragile X Syndrome (FXS) (most common inherited intellectual disability, FMR1 CGG repeat expansion)
• Gaucher Disease (GBA gene, glucocerebrosidase deficiency, hepatosplenomegaly, enzyme replacement)
• Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu, arteriovenous malformations, epistaxis)
• Homocystinuria (CBS enzyme defect, homocysteine accumulation, thrombosis, lens dislocation)
• Klinefelter Syndrome (XXY) (hypogonadism, infertility, gynecomastia, testosterone replacement)
• Krabbe Disease (Globoid Cell Leukodystrophy) (GALC gene, galactocerebrosidase deficiency, psychosine toxicity, severe demyelination, HSCT pre-symptomatically)
• Loeys-Dietz Syndrome (TGF-beta receptor mutation, aortic aneurysm, bifid uvula, arterial tortuosity)
• Maple Syrup Urine Disease (BCAA metabolism defect, encephalopathy, dietary BCAA restriction)
• Marfan Syndrome (FBN1 fibrillin-1, aortic root dilation, tall stature, ectopia lentis)
• MELAS Syndrome (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes, mtDNA mutation)
• Metachromatic Leukodystrophy (MLD) (ARSA gene, arylsulfatase A deficiency, sulfatide accumulation, most common leukodystrophy, gene therapy Libmeldy)
• Niemann-Pick Disease (sphingomyelinase deficiency, foam cells, hepatosplenomegaly, neurodegeneration)
• Neurofibromatosis Type 1 (NF1) (NF1/neurofibromin, café-au-lait spots, plexiform neurofibromas, MPNST risk, optic gliomas, selumetinib)
• Noonan Syndrome (RAS-MAPK pathway, short stature, pulmonic stenosis, webbed neck)
• Osteogenesis Imperfecta (Brittle Bone Disease) (COL1A1/COL1A2, fragile bones, blue sclerae, bisphosphonates)
• Phenylketonuria (PKU) (PAH enzyme defect, phenylalanine buildup, newborn screening, low-phe diet)
• Pompe Disease (acid maltase deficiency, glycogen storage, muscle weakness, enzyme replacement)
• Prader-Willi Syndrome (chromosome 15 paternal deletion, hyperphagia, obesity, hypotonia, GH deficiency)
• Rett Syndrome (MECP2 mutation, mostly girls, developmental regression, hand-wringing stereotypies)
• Tay-Sachs Disease (HEXA gene, GM2 gangliosidosis, neurodegeneration, cherry-red spot)
• Tuberous Sclerosis Complex (TSC) (TSC1/TSC2, hamartomas in brain/kidney/skin, epilepsy, mTOR inhibitors)
• Turner Syndrome (45,X) (monosomy X, ovarian dysgenesis, short stature, bicuspid aortic valve)
• Williams Syndrome (7q11.23 deletion, elfin facies, hypercalcemia, supravalvular aortic stenosis, hypersociability)