IllnessNoonan syndrome, differential diagnosis

NGS +

[Sanger]

Noonan syndrome causes a wide range of health problems and morphological stigma. The most common features include unusual facies (broad forehead, drooping eyelids, telecanthus), dwarfism and heart defects. The disease starts prenatally, although milder cases are diagnosed later in childhood. Then hypertrophic cardiomyopathy, variable cognitive deficits and skeletal, ectodermal and haematological abnormalities occur as well. Noonan syndrome is usually inherited in an autosomal dominant manner, with variable expressivity, therefore penetrance rates are difficult to determine. Genetically related (allelic) disorders include Noonan-like disorder, LEOPARD and cardiofaciocutaneous syndromes caused by mutations in several of the dozen or so genes that also cause Noonan syndrome. Round about half of the Noonan patients harbor PTPN11 mutations, in 13% SOS1 and in 8% LZTR1 mutations, finally in 5% RAF1- or RIT1 mutations each. <5% of the Noonan cases show KRAS mutations, all other "Noonan genes" are mutated in <1% of the affecteds. The diagnosis can be confirmed by molecular genetics in >85% of those affected, but a normal DNA result does not preclude clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1124/

• Sympt.: Short stature, facial dysmorphism, spectrum of congenital heart defects
• Alias: "Female pseudo-Turner syndrome"
• Alias: "Male Turner syndrome"
• Allelic: Adenocarcinoma of lung, somatic (BRAF)
• Allelic: Arteriovenous malformation of the brain, somatic (KRAS)
• Allelic: Bladder cancer, somatic (HRAS, KRAS)
• Allelic: Breast cancer, somatic (KRAS)
• Allelic: Cardiomyopathy, dilated, 1NN (RAF1)
• Allelic: Colorectal cancer, somatic (BRAF, NRAS)
• Allelic: Congenital myopathy with excess of muscle spindles (HRAS)
• Allelic: Epidermal nevus, somatic (NRAS)
• Allelic: Fibromatosis, gingival, 1 (SOS1)
• Allelic: Gastric cancer, somatic (KRAS)
• Allelic: Juvenile myelomonocytic leukemia (CBL, NF1)
• Allelic: Leukemia, acute myeloid, somatic (KRAS)
• Allelic: Leukemia, juvenile myelomonocytic, somatic (PTPN11)
• Allelic: Lung cancer, somatic (KRAS)
• Allelic: Melanocytic nevus syndrome, congenital, somatic (NRAS)
• Allelic: Melanoma, malignant, somatic (BRAF)
• Allelic: Melorheostosis, isolated, somatic mosaic (MAP2K1)
• Allelic: Mental retardation, XL syndromic 16 (FGD1)
• Allelic: Metachondromatosis (PTPN11)
• Allelic: Neurocutaneous melanosis, somatic (NRAS)
• Allelic: Neurofibromatosis, familial spinal (NF1)
• Allelic: Neurofibromatosis, type 1 (NF1)
• Allelic: Nevus sebaceous or woolly hair nevus, somatic (HRAS)
• Allelic: Nonsmall cell lung cancer, somatic (BRAF)
• Allelic: Oculoectodermal syndrome, somatic (KRAS)
• Allelic: Otitis media, susceptibility to (A2ML1)
• Allelic: Pancreatic carcinoma, somatic (KRAS)
• Allelic: RAS-associated autoimmune leukoproliferative disorder (KRAS)
• Allelic: RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic (NRAS)
• Allelic: Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic (HRAS, KRAS, NRAS)
• Allelic: Schwannomatosis-2, susceptibility to (LZTR1)
• Allelic: Spitz nevus or nevus spilus, somatic (HRAS)
• Allelic: Thyroid carcinoma, follicular, somatic (HRAS, NRAS)
• Allelic: Watson syndrome (NF1)
• Aarskog-Scott syndrome (FDG1)
• Atypical Noonan syndrome [panelapp] (RRAS)
• Cardiofaciocutaneous syndrome (BRAF)
• Cardiofaciocutaneous syndrome 2 (KRAS)
• Cardiofaciocutaneous syndrome 3 (MAP2K1)
• Cardiofaciocutaneous syndrome 4 (MAP2K2)
• Cherubism (SH3BP2)
• Costello syndrome (HRAS)
• Genitopatellar syndrome (KAT6B)
• Griscelli syndrome, type 1 (MYO5A)
• LEOPARD syndrome 1 (PTPN11)
• LEOPARD syndrome 2 (RAF1)
• LEOPARD syndrome 3 (BRAF)
• Legius syndrome (SPRED1)
• Neurofibromatosis-Noonan syndrome (NF1)
• Noonan syndrome 1 (PTPN11)
• Noonan syndrome 10 (LZTR1)
• Noonan syndrome 11 (MRAS)
• Noonan syndrome 12 (RRAS2)
• Noonan syndrome 2 (LZTR1)
• Noonan syndrome 3 (KRAS)
• Noonan syndrome 4 (SOS1)
• Noonan syndrome 5 (RAF1)
• Noonan syndrome 6 (NRAS)
• Noonan syndrome 7 (BRAF)
• Noonan syndrome 8 (RIT1)
• Noonan syndrome 9 (SOS2)
• Noonan syndrome [panelapp] (A2ML1)
• Noonan syndrome [panelapp] (RRAS)
• Noonan syndrome [variable, often subtle manifestations; uptodate] (CBL)
• Noonan syndrome-like [panelapp] (RRAS)
• Noonan syndrome-like disorder with loose anagen hair 1 (SHOC2)
• Noonan syndrome-like disorder with loose anagen hair 2 (PPP1CB)
• Noonan syndrome-like phenotype (A2ML1)
• Noonan syndrome? [panelapp] (RASA2)
• SBBYSS syndrome (KAT6B)