Congenital tibial hemimelia (CTH [MIM: 275220]) is a rare congenital limb deficiency that manifests as a shortened, curved, dysplastic or absent tibia with polydactyly. In previous studies, mutations of a distant sonic hedgehog (SHH) cis-regulator (ZRS) and a Shh repressor (GLI3) were identified.
Here, we admitted a 20-month-old boy who manifested with right tibial deformity, varus foot, ankle dislocation, and ipsilateral preaxial polydactyly. After genetic sequencing and data analysis, the results revealed a 443 A > G mutation in the father and a 536 C > T mutation in the mother in exon 2 of the Smoothed (SMO) gene at 7q32.1, with the coexistence of both mutant alleles in the proband/patient.
Our report suggests that even though not previously reported, SMO mutations may be associated with limb anomalies such as tibial hemimelia via Hh signaling in humans and has implications for genetic counseling.

Basal cell carcinoma (BCC) is the most common malignant tumor of the skin. Despite the indolent nature, metastatic BCC can occur, albeit rarely. Metastasis to the bone is very rare. From its approval, mBCC patients are treated with vismodegib, a selective hedgehog pathway inhibitor. Unfortunately, in recent period, it was demonstrated an emergence of drug resistance, due to Smoothened (SMO) mutation. To date, several groups are studying the effectiveness of immunotherapy in BCC. Clinical trials with Immune Checkpoint Inhibitors are ongoing. We report the rare case of a man with multiple bony metastasis, with a resistance to vismodegib, and we evaluated all manuscripts in literature reporting bone metastasis. Moreover, we review all the manuscripts in literature reporting bone metastasis, and we summarize the main therapeutic strategies, and the further perspectives.

The authors describe a clinical case of a patient with metastatic basal cell carcinoma and secondary resistance to vismodegib. A SMO G416E mutation of unknown clinical significance was found in the gene encoding the transmembrane receptor protein Smoothened (SMO) protein, which suggests a defect in the Sonic Hedgehog (SH) pathway and may cause tumor resistance to the prescribed drug. Comprehensive genomic profiling and in silico analysis have been used to diagnose the tumor.
Представлено клиническое наблюдение пациента с метастатической формой базально-клеточной карциномы со вторичной резистентностью к висмодегибу. Была обнаружена мутация с неизвестной клинической значимостью (SMO G416E) в гене, кодирующем белок SMO (трансмембранный рецептор Smoothened), что предполагает дефект в пути Sonic Hedgehog (SH) и может вызывать у опухоли резистентность к назначенному препарату. Для диагностики опухоли использовали комплексное геномное профилирование и анализ in silico.