• Family history of neuropsychiatric disorders and advanced paternal age are risk factors for ASD in the offspring previously identified in the studies in Europe and North America. What is New: • To our knowledge, this is the first study documenting risk factors for ASD in the Asian population. • Our study supports previous findings of Western countries where risk factors for ASD tend to occur in the families with neuropsychiatric illnesses particularly if such disorders came from the paternal side of the child's family.

Background: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations have been reported in patients diagnosed with IGCTs. Objectives: To describe the clinicopathologic and molecular features of KRAS mutation and the treatment outcome of children diagnosed with IGCTs. Methods: Patients diagnosed with IGCTs at the Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2016 were retrospectively reviewed. DNA was extracted from formalin-fixed, paraffin-embedded tissue and used for molecular study. Mutations in codons 12, 13, and 61 of the KRAS gene were detected using the cobas® KRAS mutation test and pyrosequencing. Results: Eighteen patients were diagnosed with IGCTs (11 males and 7 females): nine with germinomas and nine with non-germinomatous GCTs (NGGCTs). The age range of the patients was 5-14 years (median 10.5 years). Elevated markers were revealed in approximately 25% of the patients. Four patients (two with germinomas and two with NGGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was administered in 16 patients, and craniospinal radiation was administered only in patients with leptomeningeal metastasis. With a median follow-up of 26 months, overall survival was 88.9% in the patients with germinomas and 37% in the patients with NGGCTs. Mutation of the KRAS gene was detected using pyrosequencing in one patient. The mutation located at codon 61, with frequency 38.3% units, nucleotide substitution CAA > CTA, and amino acid substitution, was Q61L. The patient carrying the mutant gene was diagnosed with germinoma with cerebrospinal fluid metastasis and eventually died from treatment-related toxicity. Conclusion: Our study revealed the treatment outcomes of IGCTs in Thai children. The metastatic germinoma patient with KRAS codon 61 mutation had a poor outcome, supporting that Q61L has a clinical correlation with IGCTs.

BACKGROUND: Intracranial germ cell tumors (IGCTs) are rare, highly curable neoplasms. KRAS is a gene in the KIT/RAS signaling pathway, and KRAS mutations were reported in patients diagnosed with IGCTs. OBJECTIVES: To describe clinicopathologic, molecular features of KRAS mutation and treatment outcome of children diagnosed with IGCTs. METHODS: A retrospective review in patients diagnosed with IGCTs at Department of Pediatrics, King Chulalongkorn Memorial Hospital from 2007 to 2019. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue for the molecular study. Identifies mutations in codon 12,13 and 61 of the KRAS gene was performed by using the real-time PCR technique of the Cobas® test and pyrosequencing method. RESULTS: Eighteen patients were diagnosed with IGCTs (11 males and seven females). Age ranged from 5 to 14 years (median 10.5 years). The diagnosis was germinoma and non-germinomatous IGCTs in 9 patients each. Elevated markers were revealed in approximately 25% of patients. Four patients (2 patients with germinoma and 2 with non-germinomatous IGCTs) had leptomeningeal involvement. All patients underwent tumor biopsy and received neoadjuvant chemotherapy. Radiotherapy was given in 16 patients and craniospinal radiation (CSI) was given only in leptomeningeal metastasis. With the median follow-up of 26 months, overall survival is 88.9% in germinomas and 37% in non-germinomatous IGCTs. Mutation of the KRAS gene was detected by pyrosequencing technique in one patient. The mutation located at codon 61, frequency 38.3% units, nucleotide substitution CAA > CTA and amino acid substitution was Q61L. The patient who carries mutant gene was diagnosed germinomatous germinoma with CSF metastasis and eventually died from treatment-related toxicity. CONCLUSIONS: Our study revealed treatment outcomes of IGCTs in Thai children. We describe KRAS codon 61 mutation in metastasis germinoma patients with poor outcome, support KRAS codon 61 mutation (Q61L) may have a clinical correlation in IGCTs.