Role of Histopathology of Skin Lesions in Diagnosing MAP2K1-Positive Cardiofaciocutaneous Syndrome.

Cardiofaciocutaneous syndrome (CFC) is a rare autosomal dominant RASopathy with multisystem involvement and a wide spectrum of clinical findings. Cardiac, facial, and cutaneous features are characteristic of this developmental disorder. The diagnosis of this rare syndrome is challenging because it is based on a set of clinical features alone that are similar to those of other RASopathies, such as Noonan syndrome and Costello syndrome. Cutaneous manifestations are one of the diagnostic features of CFC syndrome, and most documented cases of CFC syndrome provide clinical descriptions of skin lesions with minimal information about the histology. In this study, we present the unique histopathology features of cutaneous lesions in a 7-month-old male child with typical facial features and cardiac abnormalities of CFC syndrome. These were acanthosis, hyperkeratosis, and squamous metaplasia of the eccrine glands with granuloma formation. Molecular analysis by next-generation sequencing showed MAP2K1 gene mutation within exon 3. In addition, we conducted a comprehensive study of the histopathology of skin lesions of CFC syndrome by various authors. On 7 years follow-up, the patient was found to have global developmental delay and muscle contractures, which are common with MAP2K1 gene mutations. Skin lesions in CFC syndrome are usually associated with BRAF mutations, and the present case is one of the few to describe the detailed histopathology of skin lesions in CFC syndrome with MAP2K1 gene mutation.