Clinical Characteristics And Genetic Analysis Of Nevoid Basal Cell Carcinoma Syndrome With Epilepsy

Background:Nevoid basal cell carcinoma syndrome?NBCCS?is a rare autosomal dominant hereditary disease.The clinical incidence of NBCCS is very low,ranging from 1:570 00 to 1:256 00.The pathogenesis of NBCNS is still unclear.Mainstream scholars believe that the occurrence of NBCNS may be abnormally related to human homologue of Drosophila patched?PTCH?.PTCH is a tumor suppressor gene,it is located at 9q22.3-q31.acting as a membrane receptor of Hedgehog protein in Hedgehog signaling pathway.Therefore,when PTCH gene changes,Hedgehog signal transduction pathway disorders,leading to the occurrence of various tumors.The main clinical manifestations of NBCCS include skin,mouth,bone,eye and central nervous system damage.Skin lesion is the most typical clinical feature of NBCCS patients,which can occur at all stages of NBCCS.Central nervous system lesions in NBCCS patients include flaky cerebral falx,tentorium cerebellum,calcification of petroclinoid ligament/sellar septum and sellar bridge.However,the above-mentioned central nervous system generally does not lead to significant clinical symptoms.Neuroblastoma is also a highly malignant brain tumour in NBCCS patients.Early diagnosis of neuroblastoma in children should be suspicious of NBCCS.Non-standardized treatment should be adopted for children with neuroblastoma complicated with NBCCS.It has important practical significance for the study of NBCCS.It not only provides guidance for the prenatal diagnosis and early prevention of NBCCS patients,but also provides a basis for the study of the pathogenesis of autosomal dominant inheritance diseases and the regulation mechanism of body growth and development.The clinical data of a family with probable NBCCS combined with epilepsy was retrospectively analyzed.Clinical diagnosis was made based on the typical manifestations,cranial and facial images according to the diagnostic criteria of NBCCS..The heterozygous deletion in the exon 20 of PTCH1 gene?c.3364 3365del?maybe a potential hot spot mutation for NBCCS,especially in patients combined with neurological manifestations,such as epilepsy.Objective:To investigate the clinical and genetic characteristics of NBCCS combined with epilepsy.Methods:In this study,a proband with epileptic seizures as the main manifestation and his family members were selected as the subjects for the study.Positive craniocervical X-ray,head CT and magnetic resonance imaging?MRI?were performed,and blood samples were taken for thyroid and parathyroid function,immune index and tumor index examination.Lumbar puncture was performed to detect CSF fluid pressure,cell number and protein content.Hematoxylin-eosin?H-E?staining was performed after excision of skin nevus.Peripheral blood of patients and their immediate family members were extracted,DNA was extracted,PTCH1 gene exon was amplified by PCR,and the amplified products were sequenced.Results:Positive craniocervical X-ray showed mandibular cysts and cystic lesions in left zygomatic soft tissue;CT showed multiple calcifications in falx cerebri and bilateral tentorium cerebellum;MRI T2 showed bilateral paraventricular white matter lesions with mild hydrocephalus.Thyroid and parathyroid function,immune index and tumor markers were normal.The cerebrospinal fluid protein level of lumbar puncture was higher than that of normal.H-E staining showed typical pathological changes in facial nevoid according to NBCCS..Next generation sequencing on the blood DNA of the proband and Family Sanger Verification confirmed heterozygous deletion at c.3364₃365del base in the exon 20 of PTCH1 gene.Conclusion:The heterozygous deletion in the exon 20 of PTCH1 gene?c.3364₃365del?maybe a potential hot spot mutation for NBCCS,especially in patients combined with neurological manifestations,such as epilepsy.