Stage M Infantile Neuroblastoma With Involvement of Falx Cerebri: Case Report and Literature Review.

Neuroblastoma is the most common extracranial solid tumor in children. When metastasis to the falx cerebri is present, it is classified as stage M; however, its behavior has not been well characterized. Here we present a case of stage M infantile neuroblastoma (NB) with involvement of the falx cerebri, and also summarize the clinical profiles of previously reported cases. Notably, all of the tumors resolved with low-dose chemotherapy alone. Although further study is needed to distinguish NBs presenting at these different intracranial locations, NB with metastasis to the falx cerebri may be categorized as MS when diagnosed at less than 18 months of age.

Comprehensive Targeted Sequencing Identifies Monogenic Disorders in Patients With Early-onset Refractory Diarrhea.

OBJECTIVES: Causes of early-onset refractory diarrhea include exudative diarrhea associated with very early-onset inflammatory bowel diseases, osmotic or secretory diarrhea, and protein-losing enteropathy. Monogenic disorders are included in these diseases, yet a comprehensive genetic analysis has not been fully established. METHODS: We established targeted gene panels covering all responsible genes for early-onset diarrhea. In total, 108 patients from 15 institutions were enrolled in this study. We collected clinical data from all patients. Seventy-three patients with exudative diarrhea, 4 with osmotic or secretory diarrhea and 8 with protein-losing enteropathy were subjected to genetic analysis. RESULTS: A total of 15 out of the 108 enrolled patients (13.9%) were identified as monogenic. We identified 1 patient with RELA, 2 with TNFAIP3, 1 with CTLA4, 1 with SLCO2A1, 4 with XIAP, 3 with IL10RA, 1 with HPS1, 1 with FOXP3, and 1 with CYBB gene mutations. We also identified 1 patient with NFKB2 and 1 with TERT mutations from the gene panel for primary immunodeficiency syndromes. The patient with refractory diarrhea caused by heterozygous truncated RelA protein expression is the first case identified worldwide, and functional analysis revealed that the mutation affected nuclear factor kappa B signaling. Genotypes were significantly associated with the clinical and pathological findings in each patient. CONCLUSIONS: We identified variable monogenic diseases in the patients and found that genes responsible for primary immunodeficiency diseases were frequently involved in molecular pathogenesis. Comprehensive genetic analysis was useful for accurate molecular diagnosis, understanding of underlying pathogenesis, and selecting the optimal treatment for patients with early-onset refractory diarrhea.An infographic for this article is available at: http://links.lww.com/MPG/B853.

Targeted Sequencing and Immunological Analysis Reveal the Involvement of Primary Immunodeficiency Genes in Pediatric IBD: a Japanese Multicenter Study.

PURPOSE: Pediatric inflammatory bowel disease (IBD) is a heterogeneous disorder caused by multiple factors. Although genetic and immunological analyses are required for a definitive diagnosis, no reports of a comprehensive genetic study of a Japanese population are available. METHODS: In total, 35 Japanese patients <16 years of age suffering from IBD, including 27 patients aged <6 years with very early-onset IBD, were enrolled in this multicenter study. Exome and targeted gene panel sequencing was performed for all patients. Mutations in genes responsible for primary immunodeficiency diseases (PID) and clinical and immunological parameters were evaluated according to disease type. RESULTS: We identified monogenic mutations in 5 of the 35 patients (14.3 %). We identified compound heterozygous and homozygous splice-site mutations in interleukin-10 receptor A (IL-10RA) in two patients, nonsense mutations in X-linked inhibitor of apoptosis protein (XIAP) in two patients, and a missense mutation in cytochrome b beta chain in one patient. Using assays for protein expression levels, IL-10 signaling, and cytokine production, we confirmed that the mutations resulted in loss of function. For each patient, genotype was significantly associated with clinical findings. We successfully treated a patient with a XIAP mutation by allogeneic cord blood hematopoietic stem cell transplantation, and his symptoms were ameliorated completely. CONCLUSIONS: Targeted sequencing and immunological analysis are useful for screening monogenic disorders and selecting curative therapies in pediatric patients with IBD. The genes responsible for PID are frequently involved in pediatric IBD and play critical roles in normal immune homeostasis in the gastrointestinal tract.

Genetic heterogeneity in 26 infants with a hypomyelinating leukodystrophy.

T2 hyperintensity of brain white matter lesions detected by magnetic resonance imaging (MRI) are characteristic of a heterogeneous group of diseases. Persistent T2 high intensity in combination with T1 iso- or high intensity of white matter in infants indicates a lack of normal myelination, that is, hypomyelination. However, the precise diagnosis of hypomyelinating leukodystrophy based solely on MRI findings can be difficult, especially in the early stage of the disease. We studied 26 patients who were diagnosed with hypomyelinating leukodystrophy according to MRI findings and clinical features to uncover their genetic etiology through chromosomal analyses, targeted gene analyses, and an array comparative genomic hybridization (aCGH) assay. Then, for the 17 patients with unexplained hypomyelination by traditional analyses, whole-exome sequencing (WES) was performed. The presumptive diagnoses were confirmed in 58 % of the enrolled patients (15/26) and involved 9 different genetic backgrounds. The most frequent backgrounds were 18q deletion syndrome and Pelizaeus-Merzbacher disease, with an incidence of 12 % (3/26) for both. The diagnostic rate of chromosomal analyses, targeted gene analyses, and aCGH was 31 % (8/26), and one patient was clinically diagnosed with Cockayne syndrome. Using WES, the following causative genes of hypomyelination were identified in six individuals (35 %, 6/17): TUBB4A, POLR3B, KCNT1, and MCOLN1, and some of those genes were pathogenic for not only hypomyelination but also dysmyelination or delayed myelination. Our findings suggested heterogeneous genetic backgrounds in patients with persistent white matter lesions. These data also indicate that WES may be a rapid and useful tool for identifying the underlying genetic causes of undiagnosed leukodystrophies.

Genomic analysis identifies candidate pathogenic variants in 9 of 18 patients with unexplained West syndrome.

West syndrome, which is narrowly defined as infantile spasms that occur in clusters and hypsarrhythmia on EEG, is the most common early-onset epileptic encephalopathy (EOEE). Patients with West syndrome may have clear etiologies, including perinatal events, infections, gross chromosomal abnormalities, or cases followed by other EOEEs. However, the genetic etiology of most cases of West syndrome remains unexplained. DNA from 18 patients with unexplained West syndrome was subjected to microarray-based comparative genomic hybridization (array CGH), followed by trio-based whole-exome sequencing in 14 unsolved families. We identified candidate pathogenic variants in 50% of the patients (n = 9/18). The array CGH revealed candidate pathogenic copy number variations in four cases (22%, 4/18), including an Xq28 duplication, a 16p11.2 deletion, a 16p13.1 deletion and a 19p13.2 deletion disrupting CACNA1A. Whole-exome sequencing identified candidate mutations in known epilepsy genes in five cases (36%, 5/14). Three candidate de novo mutations were identified in three cases, with two mutations occurring in two new candidate genes (NR2F1 and CACNA2D1) (21%, 3/14). Hemizygous candidate mutations in ALG13 and BRWD3 were identified in the other two cases (14%, 2/14). Evaluating a panel of 67 known EOEE genes failed to identify significant mutations. Despite the heterogeneity of unexplained West syndrome, the combination of array CGH and whole-exome sequencing is an effective means of evaluating the genetic background in unexplained West syndrome. We provide additional evidence for NR2F1 as a causative gene and for CACNA2D1 and BRWD3 as candidate genes for West syndrome.

[Case of brain death liver transplantation suspended because of respiratory failure after admission to the operating room].

We experienced a case in which brain death liver transplantation was suspended after admission to the operating room because the impaired oxygenation was aggravated. A 32-year-old man (weight 70 kg, height 164 cm) who had previously undergone living donor liver transplantation for Budd-Chiari syndrome developed hepatic failure 11 months after the transplantation and was enrolled in the waiting list for brain death liver transplantation. Mechanical ventilation and blood purification therapy were performed in the intensive care unit because he was in coma and his respiratory function had gradually worsened. A brain-dead donor was identified 21 days after enrollment. The patient was transported to the operating room when the donor liver arrived at our hospital. However, the surgery was suspended because his respiratory function deteriorated further after induction of general anesthesia. A patient enrolled in the brain death transplantation list often has to wait long for a donor organ. Anesthesiologists should actively participate in the preoperative management and evaluation of a patient's general status during the waiting period.

A case series of CAEBV of children and young adults treated with reduced-intensity conditioning and allogeneic bone marrow transplantation: a single-center study.

BACKGROUND: Epstein-Barr virus (EBV)-infected T or NK cells cause chronic active EBV infection (CAEBV). Allogeneic hematopoietic stem cell transplantation (HSCT) is curative treatment for CAEBV patients. However, chemotherapy prior to HSCT and optimal conditioning regimen for allogeneic HSCT are still controversial. PATIENTS AND METHODS: We retrospectively analyzed five patients with CAEBV treated with reduced-intensity conditioning (RIC) consisted of fludarabine, cyclophosphamide, and low-dose total-body irradiation followed by allogeneic bone marrow transplantation in a single institute. Only one of five patients received chemotherapy prior to transplantation. We analyzed EBV-infected cells in a patient whose EBV load increased after HSCT by T-cell repertoire assay, separation of T-cell subpopulations, in situ hybridization and microsatellite analysis. RESULTS: All five patients achieved engraftment, complete chimera, and eradication of EBV load. All patients have been alive without any serious regimen-related toxicity for more than 16 months following HSCT. However, one patient transplanted from HLA-matched sibling donor developed clonal proliferation of CD4+ Vß3+ T cells caused by monoclonal EBV infection on day 99 after transplantation. Further analysis revealed that the CD4+ Vß3+ T cells selectively harbored EBV genome, and these infected cells were derived from donor T cells. CONCLUSIONS: Allogeneic HSCT with RIC is a safe and effective treatment for better overall survival and less regimen-related toxicity in patients with CAEBV. Our first pediatric case reported in the literature suggests that we should consider the possibility of persistent EBV infection in donor T cells as well as the relapse in recipient cells if EBV load increases after allogeneic HSCT.

Reduced-intensity conditioning is effective for allogeneic hematopoietic stem cell transplantation in infants with MECOM-associated syndrome.

Mutations in the MECOM encoding EVI1 are observed in infants who have radioulnar synostosis with amegakaryocytic thrombocytopenia. MECOM-associated syndrome was proposed based on clinical heterogeneity. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for progressive bone marrow failure. However, data regarding allogeneic HSCT for this rare disease are limited. We retrospectively assessed overall survival, conditioning regimen, regimen-related toxicities and long-term sequelae in six patients treated with allogeneic HSCT. All patients received a reduced-intensity conditioning (RIC) regimen consisting of fludarabine, cyclophosphamide or melphalan, and rabbit anti-thymocyte globulin and/or low-dose total body/thoracic-abdominal/total lymphoid irradiation, followed by allogeneic bone marrow or cord blood transplantation from unrelated donors between 4 and 18 months of age. All patients survived and achieved stable engraftment and complete chimerization with the donor type. Moreover, no patient experienced severe regimen-related toxicities, and only lower grades of acute graft-versus-host disease were observed. Three patients treated with low-dose irradiation had relatively short stature compared to three patients not treated with irradiation. Therefore, allogeneic HSCT with RIC is an effective and feasible treatment for infants with MECOM-associated syndrome. Future studies are needed to evaluate the use of low-dose irradiation to avoid risks of other long-term sequelae.

Human herpes virus type 6 can cause skin lesions at the BCG inoculation site similar to Kawasaki Disease.

Kawasaki Disease (KD) is acute, febrile, multisystem vasculitis of early childhood, the detailed mechanism of which is still unclear. Skin symptoms occur in KD, such as edema of the hands and feet with subsequent desquamation and redness at the inoculation site of bacillus Calmette-Guerin (BCG). The change at the BCG inoculation site has been considered as a specific feature of KD, although its mechanism is not fully understood. We present an 11-month-old boy who developed fever with redness of the BCG site due to infection with human herpes virus type 6 (HHV6). At the age of 3 months, the patient received BCG. His fever remitted 7 days after the onset of skin redness, with sequential desquamation at the BCG site and extremities, which is not a common feature of HHV6 infection that typically lasts for 3 days. The final diagnosis was exanthema subitum. Characteristically, the HHV6 infection in our patient appeared to be associated with the invigoration of the T cell system, as represented by the elevated serum levels of soluble interleukin-2 receptor (3,490 U/ml vs. normal range 145-519 U/ml). This patient clearly showed redness and crusting at the BCG inoculation site, suggesting that HHV6 infection might cause skin changes similar to those of KD via an unknown mechanism. In addition, we suggest that the activation of the T cell system may account for the skin lesions in KD, characterized by redness and subsequent crusting of the BCG inoculation site and desquamation of the extremities.

Panax ginseng: a newly identified cause of gynecomastia.

Gynecomastia or benign proliferation of the male breast glandular tissue is not uncommon for adolescent males. Its pathogenesis has been attributed to a transient imbalance between estrogens and androgens. Ginseng is a popular herb with a long history of medicinal use. Oriental folk medicine describes it as both a tonic for restoring strength and a panacea. The term "ginseng" generally refers to a plant, Panax ginseng. Based on estrogen-like actions of Panax ginseng due to its structural similarity with estradiol, this agent could be speculated to cause gynecomastia. Here we report a 12-year-old Korean-Japanese boy with bilateral enlargement of the breasts with tenderness in the right breast, which was noticed about 1 month before his first visit to our outpatient clinic. He was diagnosed with gynecomastia based on physical, laboratory, and ultrasound examinations. Detailed questioning about his medications and supplements revealed that he had been given red ginseng extract daily to enhance his performance for 1 month before his clinical presentation. He wanted to make his body stronger as an athlete. He was recommended from his grandmother to take Panax ginseng for his purpose. After stopping this, there was no further growth of the masses and no pain when his right breast was pressed. In conclusion, physicians should consider ginseng in the investigation of gynecomastia.

[An investigation on prognostic diagnosis and therapeutic effects for peripheral facial nerve palsy].

BACKGROUND: Prognostic examinations and therapeutic strategy for peripheral facial nerve palsy are still obscure. We investigated the utility of examinations and the effects of treatment in these patients retrospectively. METHODS: A total of 301 patients with peripheral facial nerve palsy were classified into three groups: Group A, cured within two months (n = 208), Group B, cured within six months (n = 34), Group C, uncured (n = 59). Patient's characteristics, electrophysiological examinations and treatment methods were compared between the groups. RESULTS: The mean age of patients was higher in Group C than in Group A, and the lowest palsy score was higher in Group A than in another groups (P < 0.05). Sensitivity and specificity for prognostic diagnosis were higher in electroneurography rather than blink reflex and Yanagihara grading system. Cervical sympathetic nerve block and hyperbaric oxygen therapy did not affect patients' prognosis. There were not significant difference on prognosis between over 120 mg x day(-1) and 60 mg x day(-1) of prednisolone. CONCLUSIONS: Lower palsy score and higher age were risks of bad prognosis and electroneurography is useful for prognostic evaluation of peripheral facial nerve palsy. Therapeutic effects of sympathetic nerve block and hyperbaric oxygen were not entirely clarified. Administration dose of prednisolone was thought to be sufficient with 60 mg x day(-1).

[Remifentanil increases urine output in patients undergoing laparoscopic colectomy].

BACKGROUND: It has been reported that laparoscopic surgery increases stress response such as oliguria. We investigated whether anesthetic methods affect urine output during anesthesia in patients undergoing laparoscopic colectomy. METHODS: Urine output during anesthesia was compared retrospectively between general anesthesia with intravenous infusion of remifentanil, without epidural anesthesia and general anesthesia combined with epidural anesthesia, without remifentanil. Patients were excluded if they had renal failure and/or had received diuretics. 331 American Society of Anesthesiologists (ASA) physical status 1-3 patients who had undergone elective laparoscopic colectomy were enrolled in the study (remifentanil group; n = 214, epidural group; n = 117). In addition, remifentanil group was divided into two groups (higher dose group; n = 108, lower dose group; n = 106) with the median value of 0.3 g x kg(-1) x min(-1). RESULTS: Urine output during anesthesia in remifentanil group was significantly higher than epidural group, although the volume of fluid infusion was significantly less in remifentanil group. Furthermore, urine output in higher dose remifentanil group was significantly higher than the lower dose group, while there were no significant differences in the volume of fluid infusion between the two groups. CONCLUSIONS: Adequate remifentanil injection might increase urine output by preventing stress response to laparoscopic colectomy.

Clofarabine monotherapy in two patients with refractory Langerhans cell histiocytosis.

BACKGROUND: Better therapeutic options other than conventional chemotherapy for pediatric patients with refractory Langerhans cell histiocytosis (LCH) remain undetermined. CASE: We successfully treated two patients with refractory and risk organ negative LCH with clofarabine (CLO) monotherapy after recurrence. We administered total 23 courses of CLO monotherapy in patient 1 and 4 courses in patient 2. Both patients had distinct clinical manifestations but achieved a durable complete response with acceptable adverse effects of transient myelosuppression. CLO monotherapy was still effective when he had the second recurrent lesion after first completion of CLO in patient 1. We could discontinue prednisolone to control his refractory inflammation of LCH after completing CLO chemotherapy in patient 2. CONCLUSION: Although large-scale studies are warranted, CLO monotherapy could be a therapeutic option for high efficacy and feasibility besides other intensive combination chemotherapies or allogeneic hematopoietic stem cell transplantation for refractory LCH without risk organ involvement in children.

Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells.

Vascular endothelial growth factor (VEGF) signaling in endothelial cells serves a critical role in physiologic and pathologic angiogenesis. Endothelial cells secrete soluble VEGF receptor-1 (sVEGFR-1/sFlt-1), an endogenous VEGF inhibitor that sequesters VEGF and blocks its access to VEGF receptors. This raises the question of how VEGF passes through this endogenous VEGF trap to reach its membrane receptors on endothelial cells, a step required for VEGF-driven angiogenesis. Here, we show that matrix metalloproteinase-7 (MMP-7) degrades human sVEGFR-1, which increases VEGF bioavailability around the endothelial cells. Using a tube formation assay, migration assay, and coimmunoprecipitation assay with human umbilical vein endothelial cells (HUVECs), we show that the degradation of sVEGFR-1 by MMP-7 liberates the VEGF(165) isoform from sVEGFR-1. The presence of MMP-7 abrogates the inhibitory effect of sVEGFR-1 on VEGF-induced phosphorylation of VEGF receptor-2 on HUVECs. These data suggest that VEGF escapes the sequestration by endothelial sVEGFR-1 and promotes angiogenesis in the presence of MMP-7.

Tactile sensation and occlusal loading condition of mandibular premolars and molars.

The aim of the study was to investigate any correlation between tactile sensation and occlusal loading conditions of mandibular premolars and molars, by means of tactile detection threshold (TDT). TDTs of mandibular premolars and molars of twenty adults were determined by calibrated monofilaments. Occlusal force (OF) applied on each tooth at maximal-clenching was measured by a pressure-sensitive film. There was neither a correlation between the mean TDTs and the total OFs of individual participant nor in each tooth type. TDTs of the teeth on the preferred chewing side were significantly higher than those of the contralateral side. The results suggest that periodontal sensation is more related to frequency than to magnitude of loading.

[Anesthetic management for a patient with scoliosis combined with central core disease].

We gave general anesthesia to a patient with scoliosis combined with central core disease (CCD). CCD is a slowly progressive autosomal dominant congenital myopathy. CCD is presented typically in infancy with hypotonia and delay of motor development, characterized by predominantly proximal weakness pronounced in the hip girdle. Orthopedic complications are common with congenital dislocation of the hips, scoliosis and foot deformity. CCD is due to mutations in the skeletal muscle ryanodine receptor (RYR1) gene at chromosome 19q13.1, which is also implicated in the malignant hyperthermia (MH). A patient with CCD is at risk of MH, with an abnormal response to suxamethonium and volatile anesthetics. The anesthetist ought to be aware of the diagnosis of CCD and to plan anesthetic management accordingly, avoiding potentially MH-triggering agents. We used total intravenous anesthesia (TIVA) in this case, and he showed no MH symptoms perioperatively. This report demonstrates that anesthesia in a patient with CCD could be successfully maintained with TIVA.

Primary Immunodeficiencies Associated With Early-Onset Inflammatory Bowel Disease in Southeast and East Asia.

Background: Causes of early-onset inflammatory bowel disease (IBD) vary, and primary immunodeficiency diseases (PIDs) are associated with early-onset IBD as monogenic disorders. Aim: This review investigates the prevalence, clinical manifestation, genetic profile, and treatment of patients with early-onset IBD in Southeast and East Asia. Methods: A systemic review of articles reporting PID patients associated with early-onset IBD in Southeast and East Asia was conducted. Results: The prevalence of PID associated with IBD was higher than that reported in western nations, and the frequency of patients with bloody stools as an early symptom was relatively higher in monogenic diseases. A total 13 (12.0%) of 108 patients with early-onset IBD were diagnosed as PID by exome sequencing and targeted gene panel analysis in Japan, including four patients with XIAP, three with IL10RA, and two or one patient with other gene mutations. In addition, ten patients were reported as having IL-10 receptor alpha (IL-10RA) deficiency in China and Hong Kong. Allogeneic hematopoietic stem cell transplantation was performed in patients with X-linked inhibitor of apoptosis deficiency, IL-10RA deficiency, or other PID as a curative treatment, and the preferable outcome of reduced-intensity conditioning and complete resolution of IBD symptoms and dysbiosis were achieved. Conclusion: Comprehensive molecular diagnosis has been widely applied to screen for patients with PID-associated IBD in Southeast and East Asia. These results contributed to the awareness of monogenic PID in early-onset IBD patients and their differences in clinical manifestations and genetic profiles compared to the patients in western counties.

Ruxolitinib treatment of a patient with steroid-dependent severe autoimmunity due to STAT1 gain-of-function mutation.

Signal transducer and activator of transcription 1 gain-of-function (STAT1 GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC). We report the effect of oral ruxolitinib, an inhibitor of Janus kinase (JAK) family tyrosine kinases, on the clinical and immune status of a 3-year-old male with steroid-dependent severe autoimmunity due to a STAT1 GOF T385M mutation. The patient's susceptibility to infection improved with antimicrobial prophylaxis and immunoglobulin replacement therapy, but he continued to exhibit severely disabling symptoms of autoimmunity. More than one-third of patients with STAT1 GOF mutations present with autoimmune manifestations, and this patient's mutation was reported to cause CMC with autoimmunity. We analyzed the interleukin (IL)-17A and IFN-γ levels and immunophenotype by flow cytometry before and during treatment with ruxolitinib. The peripheral IL-17A level did not increase, but the IFN-γ level decreased after 4 months of therapy. The STAT1 phosphorylation level decreased significantly upon stimulation of patient cells with IFN-γ. Clinically, cytomegalovirus reactivation occurred, but was controlled. No other adverse effect was noted. We report the potential of JAK1/2 inhibition with ruxolitinib for both CMC and steroid-dependent autoimmunity. However, long-term administration is necessary, as the effect is not sustained after treatment is discontinued.

Periodontal tactile sensation and occlusal loading condition of autotransplanted teeth: A retrospective pilot study.

PURPOSE: The objectives of this retrospective pilot study were: (1) to examine the occlusal properties (periodontal tactile sensation, occlusal force support ability, dynamic tooth mobility, occlusal force, contact area, preferred chewing side and main occluding area) of autotransplanted teeth with no clinical complications after transplantation (postoperative periods from 1 to 7 years). METHODS: Three groups were formed from 20 subjects (23 teeth in each group): autotransplanted teeth (ATP group), teeth contralateral to the recipient site (control group A), and teeth contralateral to the donor site (control group B). RESULTS: The tactile detection threshold of the ATP group was higher than both the control groups, and the individual occlusal force was significantly lower than control group A. The occlusal force ratio and the occlusal contact area ratio were significantly lower in the ATP group than in both control groups, while the mobility was similar in all groups. Eight out of 20 subjects chose the autotransplanted teeth side as the preferred chewing side. Especially when the recipient site was the first molar, the ATP of these subjects were included in the main occluding area. The pocket depth of the three groups was within the normal range. CONCLUSIONS: These results demonstrate that teeth autotransplantation can achieve a mastication efficiency and periodontal condition similar to normal teeth; however, without proper healing, the periodontal sensation of autotransplanted teeth may be inferior to that of normal teeth (<250).

Dramatic response after functional hemispherectomy in a patient with epileptic encephalopathy carrying a de novo COL4A1 mutation.

We describe the first case of a successful functional hemispherectomy in a patient with epileptic encephalopathy and a de novo collagen type IV alpha 1 (COL4A1) mutation. A 4-year-old girl was COL4A1 mutation-positive and suffered from drug-resistant epilepsy, hemiplegia, and developmental delay. Magnetic resonance imaging detected no porencephaly, and she had no cataract or renal abnormality. Following a presurgical evaluation for epilepsy, she underwent a functional hemispherectomy. She has been seizure free with no intracranial hemorrhage or other perioperative complications. Patients with a COL4A1 mutation have an increased risk for intracranial hemorrhage because of disrupted integrity in the vascular basement membrane due to the mutation. After weighing the risks and benefits to these patients, epilepsy surgery may not be absolutely contraindicated. Furthermore, pediatric neurologists should be aware of an undiagnosed COL4A1 mutation when a patient presents with an unexplained neurological phenotype, such as mild hemiparesis, even in the absence of porencephaly.