IllnessCostello syndrome, differential diagnosis

NGS +

[Sanger]

Costello syndrome is initially characterized by delayed development, loose skin folds, unusually flexible joints and prominent facial features (e.g. large mouth with full lips). Cardiac problems are common, including arrhythmias, structural heart defects and hypertrophic cardiomyopathy. Infants with Costello syndrome may be relatively large at birth, then because of feeding problems they grow more slowly than other children (short stature with low growth hormone levels). Furthermore, muscular hypotonia, Chiari I malformation, skeletal abnormalities, dental problems and visual disturbances may be noticeable. Early in childhood, there is an increased risk of developing papillomas, rhabdomyosarcomas, neuroblastomas and a certain form of bladder cancer. The symptoms of Costello syndrome overlap with those of cardiofaciocutaneous (CFC) and Noonan syndromes, although the distinction becomes clearer in older children. The mode of inheritance is formally autosomal dominant with complete penetrance, but almost all reported cases have arisen from spontaneous activating point mutations. The DNA diagnostic yield is unknown, mainly because of closely related syndromes.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1507/

• Alias: Faciocutaneoskeletal syndrome (HRAS)
• 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 (BFAF, 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: 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: Metachondromatosis (PTPN11)
• Allelic: Neurocutaneous melanosis, somatic (NRAS)
• Allelic: Nevus sebaceous or woolly hair nevus, somatic (HRAS)
• Allelic: Nonsmall cell lung cancer, somatic (BRAF)
• Allelic: Oculoectodermal syndrome, somatic (KRAS)
• 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: Spitz nevus/nevus spilus, somatic (HRAS)
• Allelic: Thyroid carcinoma, follicular, somatic (HRAS, NRAS)
• Allelic: Wilms tumor, somatic (GPC3)
• Cardiofaciocutaneous syndrome (BRAF)
• Cardiofaciocutaneous syndrome 2 (KRAS)
• Cardiofaciocutaneous syndrome 3 (MAPK1)
• Cardiofaciocutaneous syndrome 4 (MAP2K2)
• Costello syndrome (HRAS)
• Noonan syndrome 1 (PTPN11)
• 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 with multiple lentigenes - LEOPARD syndrome 1 (NRAS)
• Noonan syndrome with multiple lentigenes - LEOPARD syndrome 2 (RAF1)
• Noonan syndrome with multiple lentigenes - LEOPARD syndrome 3 (BRAF)
• Noonan syndrome-like with loose anagen hair 1 (SHOC2)
• Noonan syndrome-like with loose anagen hair 2 (PPP1CB)
• Simpson-Golabi-Behmel syndrome, type 1 (GPC3)