IllnessCardio-facio-cutaneous syndrome, differential diagnosis

NGS +

[Sanger]

Most patients with cardiofaciocutaneous syndrome (CFCS), a RASopathy, have cardiac defects (pulmonary stenosis, atrial septal defects, hypertrophic cardiomyopathy). The facial features of CFCS are characteristic: high forehead (narrowed at the temples), short nose, hypertelorism, outward/downward palpebral fissures, ptosis, small chin, and low-set ears. Overall, the face is broad and long. Skin abnormalities occur in almost all CFCS patients: dry/rough skin, nevi, wrinkled palms/soles and keratosis pilaris. CFCS patients also have thin, dry, curly hair and sparse or absent eyelashes and eyebrows. Infants with CFCS typically exhibit muscle hypotonia, feeding difficulties and failure to thrive. Other features of CFCS may include macrocephaly, short stature, vision problems and seizures. CFCS patients develop delayed with moderate to severe intellectual deficits. The symptoms of CFCS overlap significantly with those of Costello and Noonan syndrome. These three syndromes differ substantially in molecular genetics and some specific symptoms; however, it may still be difficult to separate these syndromes, especially in infancy. Unlike Costello syndrome, cancer development does not appear to be a major feature of CFCS. CFCS is inherited in an autosomal dominant manner. BRAF gene mutations are most common in CFCS (>75%), less common (>15% mutations) in the MAP2K1 or MAP2K2 genes and <5% in the KRAS gene. Negative molecular genetic findings in typical clinical situations most likely point to differential diagnoses, e.g. Costello or Noonan syndrome.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1186/

• Allelic: Cardiomyopathy, dilated, 1NN (RAF1)
• Allelic: Congenital myopathy with excess of muscle spindles (HRAS)
• Allelic: Fibromatosis, gingival, 1 (SOS1)
• Allelic: Juvenile myelomonocytic leukemia (CBL)
• Allelic: Leukemia, juvenile myelomonocytic (NF1)
• Allelic: Melorheostosis, isolated, somatic mosaic (MAP2K1)
• Allelic: Metachondromatosis (PTPN11)
• Allelic: Neurofibromatosis, familial spinal (NF1)
• Allelic: Ovarian carcinoma (RRAS2)
• Allelic: RAS-associated autoimmune leukoproliferative disorder (KRAS)
• Allelic: Schwannomatosis-2, susceptibility to (LZTR1)
• Allelic: Watson syndrome (NF1)
• Cardiofaciocutaneous syndrome (BRAF)
• Cardiofaciocutaneous syndrome 2 (KRAS)
• Cardiofaciocutaneous syndrome 3 (MAP2K1)
• Cardiofaciocutaneous syndrome 4 (MAP2K2)
• Costello syndrome (HRAS)
• LEOPARD syndrome 1 (PTPN11)
• LEOPARD syndrome 2 (RAF1)
• LEOPARD syndrome 3 (BRAF)
• Legius syndrome (SPRED1)
• Neurofibromatosis, type 1 (NF1)
• Neurofibromatosis-Noonan syndrome (NF1)
• Noonan syndrome (RASA2)
• 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-like disorder (RREB1)
• Noonan syndrome-like disorder with loose anagen hair 2 (PPP1CB)
• Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (CBL)
• Noonan syndrome-like with loose anagen hair 1 (SHOC2)