Mastocytosis in a Case of Noonan Syndrome Caused by a De Novo Pathogenic CBL Variant.

Noonan syndrome is an autosomal dominant disease characterized by multi-organ disorders caused by variants of genes involved in the RAS/MAPK signaling pathway. The nine causative genes including PTPN11 and CBL have been identified. Mastocytosis is a disease characterized by mast cell proliferation in skin, bone marrow, and other organs. To date, no previous cases of Noonan syndrome with mastocytosis caused by a pathogenic CBL variant have been reported. A boy was diagnosed with Noonan syndrome at 8 months of age with facial features and minor anomaly of his body. He presented with brown nodules of 5-10 mm on his body since the age of 2 months. The patient was diagnosed with mastocytosis by a biopsy specimen from brown nodules, which showed infiltration of mast cells. Whole-exome sequencing of the parent-patient trio revealed a de novo pathogenic CBL variant. The occurrence of mastocytosis may be a cue for the analysis of the CBL gene in Noonan syndrome. The CBL gene is involved in mastocytosis and various cancers. In the case of the pathogenic variant, long-term follow-up for the risk of cancers related to the CBL variant is necessary.

Clinical course of a Japanese patient with developmental delay linked to a small 6q16.1 deletion.

There is only one report of patients with developmental delay due to a 6q16.1 deletion that does not contain the SIM1 gene. A 3-year-old female showed strabismus, cleft soft palate, hypotonia at birth, and global developmental delay. Exome sequencing detected a de novo 6q16.1 deletion (chr6: 99282717-100062596) (hg19). The following genes were included in this region: POU3F2, FBXL4, FAXC, COQ3, PNISR, USP45, TSTD3, CCNC, and PRDM13.