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To assess the clinical significance of repeated head imaging in children with minor blunt force head trauma who underwent computed tomography (CT), limited to those who exclude with very low risk of important traumatic brain injury. We conducted a retrospective cohort study of children aged under 24 months with minor head trauma who underwent repeated head imaging and initial CT scans according to the Pediatric Emergency Care Applied Research Network (PECARN) rules. We enrolled 741 children and 110 with skull fracture (SF). Of the 96 patients with SF on initial CT who received head magnetic resonance imaging (MRI) a few days later, 36 (37.5%) patients' initial CT findings revealed intracranial injury in addition to SF. The number of children who exhibited new intracranial findings on follow-up MRI among those with isolated SF without intracranial damage and those with SF and intracranial injury on initial CT was 25/60 (40.7%) and 14/36 (38.9%), respectively. Subcutaneous hematoma on arrival and intersection with the coronal suture and lines of fracture were significantly associated with new intracranial findings. Four children with SF and intracranial injury on initial CT received neurosurgical intervention. No intervention was needed for those with isolated SF. We demonstrated that a proportion of children with head trauma had new findings on follow-up MRI, particularly in those without very low risk of clinically important traumatic brain injury. Patients who exhibit new intracranial MRI findings that satisfy the PECARN rules may not require neurosurgical intervention if their initial CT finding is isolated SF.
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Imagen por Resonancia Magnética , Fracturas Craneales , Tomografía Computarizada por Rayos X , Humanos , Fracturas Craneales/diagnóstico por imagen , Masculino , Femenino , Lactante , Estudios Retrospectivos , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Preescolar , Traumatismos Craneocerebrales/diagnóstico por imagen , Traumatismos Craneocerebrales/complicaciones , Recién NacidoRESUMEN
Limited dorsal myeloschisis (LDM) is characterized by a fibroneural tethering stalk linking the skin lesion to the underlying spinal cord. LDM without an extradural stalk is rare. A full-term boy was noted at birth to have a dimple in the upper back (dorsal skin of the lower thoracic region). Computed tomographic scan showed spina bifida at the T9-12 vertebral level and osteochondral tissue at the T10 level. Magnetic resonance imaging (MRI) demonstrated a tiny dorsal lipoma at the T8 vertebral level, but the intradural tethering tract was not apparent. At 18 days of age, the congenital dermal sinus (CDS) tract started from the dimple and terminated at the osteochondral tissue, without continuity of the dura mater, and the osteochondral tissues were resected. At age 2 years 8 months, he developed spastic paresis of the right foot. On MRI, the tethering tract from the dorsal lipoma became apparent. During the second surgery at age 2 years 11 months, the intradural stalk started from the dorsal lipoma and joined the inner surface of the dura mater was untethering from the cord. Postoperatively, right spastic paresis was improved. Histological examination of the intradural stalk revealed the distribution of S100-immunopositive peripheral nerve fibers, which is one of the histopathological hallmarks of LDM. We speculated that the extradural stalk with coexisting CDS originally linked from the skin lesion subsequently regressed and was replaced by fibroadipose tissue with osteochondral tissue migration. Intradural exploration should always be seriously considered in these disorders of persisting neurocutaneous connection.
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Lipoma , Meningomielocele , Enfermedades de la Piel , Espina Bífida Oculta , Disrafia Espinal , Masculino , Recién Nacido , Humanos , Preescolar , Espasticidad Muscular , Piel/patología , Meningomielocele/patología , Enfermedades de la Piel/patología , Imagen por Resonancia Magnética/métodosRESUMEN
Noonan syndrome (NS) is characterized by distinctive craniofacial appearance, short stature, and congenital heart disease. Approximately 80% of individuals with NS harbor mutations in genes whose products are involved in the RAS/mitogen-activating protein kinase (MAPK) pathway. However, the underlying genetic causes in nearly 20% of individuals with NS phenotype remain unexplained. Here, we report four de novo RRAS2 variants in three individuals with NS. RRAS2 is a member of the RAS subfamily and is ubiquitously expressed. Three variants, c.70_78dup (p.Gly24_Gly26dup), c.216A>T (p.Gln72His), and c.215A>T (p.Gln72Leu), have been found in cancers; our functional analyses showed that these three changes induced elevated association of RAF1 and that they activated ERK1/2 and ELK1. Notably, prominent activation of ERK1/2 and ELK1 by p.Gln72Leu associates with the severe phenotype of the individual harboring this change. To examine variant pathogenicity in vivo, we generated zebrafish models. Larvae overexpressing c.70_78dup (p.Gly24_Gly26dup) or c.216A>T (p.Gln72His) variants, but not wild-type RRAS2 RNAs, showed craniofacial defects and macrocephaly. The same dose injection of mRNA encoding c.215A>T (p.Gln72Leu) caused severe developmental impairments and low dose overexpression of this variant induced craniofacial defects. In contrast, the RRAS2 c.224T>G (p.Phe75Cys) change, located on the same allele with p.Gln72His in an individual with NS, resulted in no aberrant in vitro or in vivo phenotypes by itself. Together, our findings suggest that activating RRAS2 mutations can cause NS and expand the involvement of RRAS2 proto-oncogene to rare germline disorders.
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Mutación con Ganancia de Función , Mutación de Línea Germinal , Proteínas de la Membrana/genética , Proteínas de Unión al GTP Monoméricas/genética , Síndrome de Noonan/etiología , Pez Cebra/crecimiento & desarrollo , Secuencia de Aminoácidos , Animales , Niño , Preescolar , Exoma , Femenino , Humanos , Masculino , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Proteínas de Unión al GTP Monoméricas/química , Proteínas de Unión al GTP Monoméricas/metabolismo , Síndrome de Noonan/patología , Fenotipo , Conformación Proteica , Proto-Oncogenes Mas , Homología de Secuencia , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
Craniosynostosis(CS)is now being diagnosed early as Japanese parents have become more conscious of the infants' skull shape. Endoscopy-assisted suturectomy(EAS)is a surgical treatment for early infants in combination with postoperative helmet cranial remodeling. Here we report our operative experiences with EAS for the treatment of CS. EAS is minimally invasive and has yielded good results when performed in combination with helmet therapy. However, transfusion for almost half of patients and additional surgery for syndromic patients were required. We will further develop the bone resection technique and hemostasis methods.
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Craneosinostosis , Dispositivos de Protección de la Cabeza , Lactante , Humanos , Craneosinostosis/diagnóstico por imagen , Craneosinostosis/cirugía , Endoscopía/métodos , Aparatos Ortopédicos , Cráneo/cirugíaRESUMEN
The aim of the surgery for craniosynostosis is to release increased intracranial pressure and to normalize cranial shape. The procedure has developed so far in Japan, from a simple strip craniectomy before 1960s through a total calvarial remodeling after 1970s and later methods of 1990s, such as distraction and its modifications applying to the posterior cranium. Since a distracter needs certain hardness and thickness of the bone, the surgery has to be stood by until 5 to 6 months of age. Modified Jimenez procedure, as a latest option, were applied for very early years of 10 patients with several types of craniosynostosis, in our team in the past 3 years. The experience was small with short follow-up; the results are all good in those volume change and shape. The procedure proved to be another alternative especially prior to posterior distraction of syndromic patients in terms of positive and expedited control in an earlier surgical management.
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Craneosinostosis/cirugía , Osteogénesis por Distracción/métodos , Suturas Craneales/cirugía , Craneotomía , Femenino , Humanos , Lactante , Japón , Masculino , Procedimientos de Cirugía Plástica/métodos , SíndromeRESUMEN
INTRODUCTION: Megalencephaly capillary malformation (MCAP) is a syndrome involving brain overgrowth, characterized by megalencephaly, capillary malformations, asymmetric growth, polymicrogyria, polydactyly, and syndactyly. Cerebellar tonsillar herniation (CTH) and ventriculomegaly are also observed in over half the patients with this syndrome. Early sudden death has been reported in MCAP, but its causes and the surgical strategies for its prevention remain unclear. CASE REPORT: Here, we report on a patient with MCAP who died suddenly at 5 months of age. He presented with progressive macrocephaly and hypotonia. MRI performed at 4 months of age showed tight posterior fossa, bilateral perisylvian polymicrogyria, enlargement of the straight sinus, and a thickened corpus callosum. However, since the patient did not exhibit capillary malformation, polydactyly, or syndactyly, a definitive diagnosis of MCAP could not be made. He died suddenly while asleep at home 1 month later. The sudden death of MCAP patients was previously attributed to CTH, convulsion, or arrhythmia. In this case, progressive cerebellar enlargement appeared to be the underlying cause. After the patient's death, using his preserved DNA, a missense mutation in the AKT3 gene was identified. Vakt murine thymoma viral oncogene homologue (AKT) is a serine-threonine kinase that functions in the mammalian target of rapamycin (mTOR) pathway and plays an important role in cell proliferation. CONCLUSION: Accurate early diagnosis, including imaging and genetic analyses, and the recognition and treatment of critical conditions are required to prevent the sudden death of patients with MCAP.
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Capilares/anomalías , Muerte Súbita , Megalencefalia/genética , Mutación/genética , Proteínas Proto-Oncogénicas c-akt/genética , Malformaciones Vasculares/genética , Humanos , Lactante , Masculino , Megalencefalia/complicaciones , Malformaciones Vasculares/complicacionesRESUMEN
The effects of airbag deployment in motor vehicle accidents (MVA) on the fetus are poorly understood. A 22-year-old woman at 24 weeks of gestation collided with a telephone pole while driving. She was restrained and an airbag deployed. Although she had no major injuries, she experienced decreased fetal movements. Fetal heart rate (FHR) monitoring revealed loss of variability without any evidence of abruptio placentae, and 4 days later, the variability spontaneously recovered. Two weeks after the MVA, ultrasonography showed unilateral ventricular dilatation suggestive of fetal brain injury. Magnetic resonance imaging revealed subdural hematoma, intraventricular hemorrhage and cystic lesions, interpreted as indirect (hypoxic-ischemic) and direct (hemorrhagic) intracranial injuries. After MVA with airbag deployment, FHR monitoring can show a transient loss of variability, which may precede the appearance of fetal brain injury.
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Airbags/efectos adversos , Lesiones Encefálicas/diagnóstico , Enfermedades del Sistema Nervioso/etiología , Efectos Tardíos de la Exposición Prenatal/etiología , Lesiones Prenatales/diagnóstico , Accidentes de Tránsito , Lesiones Encefálicas/etiología , Lesiones Encefálicas/fisiopatología , Preescolar , Femenino , Feto , Frecuencia Cardíaca Fetal , Humanos , Embarazo , Lesiones Prenatales/etiología , Lesiones Prenatales/fisiopatología , Adulto JovenRESUMEN
Craniosynostosis (CS) can develop in the fetal period, but it is difficult to diagnose prenatally. In this case, a 3-month-old female baby developed extensive subgaleal hematoma and severe anemia after vacuum-assisted delivery. Her computed tomography showed bilateral lambdoid and sagittal synostosis (BLSS) with a depressed fracture of the right parietal bone. She was referred to our hospital for treatment of the CS. At 4 months of age, she underwent bilateral lambda and sagittal suturectomy and foramen magnum decompression. CS may result in trauma at delivery, because CS disturbs fetal head molding during delivery and disrupts passage through the birth canal. In particular, the risk of severe peripartum trauma is thought to increase in cases of CS with multiple suture fusions, such as those observed in BLSS, due to the strong inhibition of this process of passage through the birth canal. Therefore, if the delivery is abnormally prolonged or if the infant has a massive subgaleal hematoma, it is important to perform evaluations for CS after birth.
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BACKGROUND: Lesions associated with a thickened pituitary stalk (TPS lesions) revealed by magnetic resonance imaging have a diverse pathology. Accordingly, for clinical decision-making, it is necessary to make a diagnosis based on histopathological examination of the TPS lesions. The objectives of this study were to review endoscopic biopsies of TPS lesions and to assess the surgical strategy for treating these lesions. METHODS: Eleven patients (four males and seven females) aged from 6 to 75 years underwent endoscopic biopsy of a TPS lesion between 2006 and 2011 at University of Niigata. The relationships of the extent of lesions with surgical approaches were retrospectively examined. RESULTS: Among the 11 patients, a biopsy was performed via an endoscopic transsphenoidal approach for five with intrasellar lesions; via an endoscopic extended transsphenoidal approach for two with localized TPS lesions; and via an endoscopic intraventricular approach for four with the lesion protruding from the infundibulum. Histopathological examinations of all the lesions confirmed diagnoses of germinoma in four patients, hypophysitis in three, Langerhans cell histiocytosis in two, craniopharyngioma in one, and cancer metastasis in one. None of the 11 patients had further deterioration of pituitary function postoperatively. CONCLUSIONS: Endoscopic biopsy of TPS lesions is a less invasive alternative to open biopsy requiring transcranial surgery. The endoscopic transsphenoidal approach is most suitable for biopsies of TPS lesions associated with intrasellar lesions. Otherwise, the endoscopic intraventricular approach seems reasonable for intraventricular lesions protruding from the infundibulum, and the endoscopic extended transsphenoidal approach appears appropriate for localized TPS lesions.
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Biopsia/métodos , Endoscopía , Enfermedades de la Hipófisis/patología , Enfermedades de la Hipófisis/cirugía , Hipófisis/patología , Adolescente , Adulto , Anciano , Niño , Craneofaringioma/patología , Craneofaringioma/cirugía , Femenino , Germinoma/patología , Germinoma/cirugía , Histiocitosis de Células de Langerhans/patología , Histiocitosis de Células de Langerhans/cirugía , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Hipófisis/cirugía , Estudios Retrospectivos , Adulto JovenRESUMEN
While the standard management for posthemorrhagic hydrocephalus (PHH) has not been determined, many patients initially receive temporary treatment such as a ventricular drainage, a ventricular reservoir, or a ventriculosubgaleal shunt. Subsequently, approximately 15% of patients with PHH will require permanent cerebrospinal fluid diversion. Shunt placement is most commonly performed for PHH as permanent treatment. However, shunting still has high complication rates. Since the development of the neuroendoscopic technique has progressed, and indication has been expanded, endoscopic third ventriculostomy with or without choroid plexus cauterization has performed more frequently in recent years in patients with PHH. In this paper, the permanent treatment for PHH will be reviewed based on the latest evidence.
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BACKGROUND: Molding helmet therapy is used routinely for moderate to severe deformational plagiocephaly. However, there have been few reports of its use for deformational brachycephaly (DB). The incidence and severity of DB are high in the Asian population, including Japanese people, but there are no reports of treatment for severe cases. The current study showed significant improvement even in severe DB with various deformities. The difference in improvement according to the morphologic classification was investigated. METHODS: The study included 47 patients treated with helmet therapy for DB with a cephalic index of greater than 100%. Three-dimensional head scans were used for classification and measurement. DB was classified into four types according to the position of the eurion and the presence of deformational plagiocephaly. The therapeutic effect was determined by changes in cephalic index and cranial asymmetry. RESULTS: Patients exhibited a mean change of 8.0% in cephalic index and 6.4 mm in cranial asymmetry. An older age at initiation was associated with less change in both cephalic index and cranial asymmetry. A significant difference in the amount of cephalic index change was observed depending on the position of the eurion when the starting age was 6 months or older ( P < 0.05). CONCLUSIONS: Molding helmet therapy for severe DB results in significant morphological improvement. However, depending on the position of the eurion, the effect of treatment may be decreased if it is started too late. It is necessary to understand the difference in improvement depending on the morphology and to ensure early intervention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.
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Craneosinostosis , Plagiocefalia no Sinostótica , Humanos , Lactante , Plagiocefalia no Sinostótica/terapia , Resultado del Tratamiento , Dispositivos de Protección de la Cabeza , Craneosinostosis/terapia , IncidenciaRESUMEN
INTRODUCTION: In infants who have suffered head trauma there are two possible explanations for retinal hemorrhage (RH): direct vitreous shaking and occurrence in association with intracranial lesions. Which possibility is more plausible was examined. MATERIAL AND METHODS: This multicenter, retrospective study reviewed the clinical records of children younger than four years with head trauma who had been diagnosed with any findings on head computed tomography (CT) and/or magnetic resonance imaging (MRI). Of 452 cases, 239 underwent an ophthalmological examination and were included in this study. The relationships of RH with intracranial findings and the cause of injury were examined. RESULT: Odds ratios for RH were significant for subdural hematoma (OR 23.41, p = 0.0004), brain edema (OR 5.46, p = 0.0095), nonaccidental (OR 11.26, p<0.0001), and self-inflicted falls (OR 6.22, p = 0.0041). CONCLUSION: Although nonaccidental, brain edema and self-inflicted falls were associated with RH, subdural hematoma was most strongly associated with RH.
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Edema Encefálico , Maltrato a los Niños , Traumatismos Craneocerebrales , Preescolar , Humanos , Lactante , Edema Encefálico/complicaciones , Maltrato a los Niños/diagnóstico , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/diagnóstico por imagen , Pueblos del Este de Asia , Hematoma Subdural/diagnóstico por imagen , Hematoma Subdural/etiología , Hemorragia Retiniana/etiología , Hemorragia Retiniana/complicaciones , Estudios RetrospectivosRESUMEN
Background: Dandy-Walker syndrome (DWS) is a well-known developmental anomaly. An occipital meningocele (OMC) is recognized as a malformation that is relatively often associated with DWS, but the association of DWS with OMC has been reported in approximately 40 cases. We present herein a rare clinical course of DWS with OMC, in which the sac was small at birth and became progressively larger. Case Description: A 5-day-old baby boy was referred to our hospital due to OMC. He was born at 33 gestational weeks due to premature rupture of the membranes. He was diagnosed as having DWS associated with OMC. The OMC was covered with skin and its maximum diameter at birth was 3 cm. Magnetic resonance imaging showed an occipital bone defect and continuity of the fourth ventricle, posterior fossa cyst, and OMC sac. The aqueduct was patent, and no hydrocephalus was found. The OMC sac increased progressively with moderate hydrocephalus and reached 7 cm at the age of 54 days when his weight was 2508 g. A cystoperitoneal shunt and repair were performed after sinus venography by contrast computed tomography (CT). At the age of 1 year and 8 months, he had moderate developmental disabilities. Conclusion: In most cases reported, the OMC was relatively small, and large and giant sizes were reported in only six cases. Almost all cases remained the same size as at birth and underwent surgical intervention as early as possible. It was possible to understand the relationship between the occipital bone defect and abnormal running of sinuses such as the superior sagittal sinus, torcular Herophili, and transverse sinus preoperatively from the CT venography (CTV) image. CTV may be an effective and important method for safely performing repair and shunt.
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The organic light-emitting diode (OLED) display delivers a bright and high-contrast image compared to the liquid crystal display. The first experience of neuroendoscopic surgery using an OLED display was reported and its stereoscopic effect emphasized.
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Ventrículos Cerebrales/cirugía , Luz , Iluminación/instrumentación , Neuroendoscopía/instrumentación , Compuestos Orgánicos/química , HumanosRESUMEN
OBJECTIVE: The medical history of injury given by parents of infants and toddlers with head trauma may not be accurate or completely true. The purpose of this study was to examine the relationship between subdural hematoma (SDH) due to nonaccidental injury and mechanisms of injury provided by caregivers. METHODS: Our multicenter study group retrospectively reviewed the clinical records of children younger than 4 years with head trauma who have been diagnosed with any finding on head computed tomography (CT) and/or magnetic resonance imaging (MRI). A total of 84 cases of subdural hematomas with retinal findings, including cases reported to the child guidance center and traffic and birth injuries, were included in the study. They were classified by the mechanism of injury provided by the caregivers. Clinical findings were reviewed and classified into nonaccidental and accidental groups. The mechanisms of the injuries were examined by multivariable analysis to identify which ones were statistically associated with nonaccidental injuries. RESULTS: Of the 84 patients with SDHs, 51 were classified into the nonaccidental group, and 33 children were classified into the accidental group. In 19 patients with a chief complaint of convulsion who had SDH but no episode of trauma, 18 were classified into the nonaccidental group. On multivariable analysis, unexplained convulsions (odds ratio: 12.04, 95% confidence interval: 1.44-100.49) were significantly associated with increased odds of nonaccidental injury. CONCLUSIONS: In the present study, there was a relationship between nonaccidental injury and unexplained SDH with a chief complaint of convulsion.
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Maltrato a los Niños , Traumatismos Craneocerebrales , Preescolar , Humanos , Lactante , Maltrato a los Niños/diagnóstico , Traumatismos Craneocerebrales/complicaciones , Traumatismos Craneocerebrales/diagnóstico por imagen , Hematoma Subdural/diagnóstico por imagen , Hematoma Subdural/etiología , Japón/epidemiología , Estudios Retrospectivos , Convulsiones/complicacionesRESUMEN
OBJECTIVE: Subdural hematoma in infants or toddlers has often been linked to abuse, but it is not clear how many cases actually occur and how many are suspected of abuse. The purpose of this study was to investigate subdural hematoma in infants and toddlers in Japan. METHODS: This multicenter, retrospective study reviewed the clinical records of children younger than 4 years with head trauma who were diagnosed with any finding on head computed tomography (CT) and/or magnetic resonance imaging (MRI), such as skull fracture and/or intracranial injury. A total of 452 children were included. The group suspected to have been abused was classified as nonaccidental, and the group considered to have been caused by an accident was classified as accidental. Subdural hematoma and other factors were examined on multivariate analysis to identify which factors increase the risk of nonaccidental injuries. RESULTS: Of the 452 patients, 158 were diagnosed with subdural hematoma. Subdural hematoma was the most common finding intracranial finding in head trauma in infants and toddlers. A total of 51 patients were classified into the nonaccidental group, and 107 patients were classified into the accidental group. The age of patients with subdural hematoma showed a bimodal pattern. The mean age of the accidental group with subdural hematoma was significantly older than that in the nonaccidental group (10.2 months vs 5.9 months, respectively. p < 0.001). Multivariate analysis showed that patients under 5 months old, retinal hemorrhage, and seizure were significant risk factors for nonaccidental injury (odds ratio (OR) 3.86, p = 0.0011; OR 7.63, p < 0.001; OR 2.49, p = 0.03; respectively). On the other hand, the odds ratio for subdural hematoma was 1.96, and no significant difference was observed (p = 0.34). CONCLUSIONS: At least in Japanese children, infantile subdural hematoma was frequently observed not only in nonaccidental but also in accidental injuries. In infants with head trauma, age, the presence of retinal hemorrhage, and the presence of seizures should be considered when determining whether they were abused. Subdural hematoma is also a powerful finding to detect abuse, but care should be taken because, in some ethnic groups, such as the Japanese, there are many accidental cases.
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Accidentes , Hematoma Subdural , Fracturas Craneales , Tomografía Computarizada por Rayos X , Femenino , Hematoma Subdural/diagnóstico por imagen , Hematoma Subdural/epidemiología , Humanos , Lactante , Japón/epidemiología , Masculino , Estudios Retrospectivos , Fracturas Craneales/diagnóstico por imagen , Fracturas Craneales/epidemiologíaRESUMEN
To discuss the computed tomography (CT) and magnetic resonance (MR) findings of posterior fossa epidural hematoma (PFEDH) mimicking sinus thrombosis, we present two pediatric cases with the PFEDH extending along the sigmoid sinus groove evaluated by MR imaging (MRI) and MR venography (MRV). T2-weighted coronal MRI can diagnose both patency of the sigmoid sinus and epidural hematoma extending along the sinus groove. Phase-contrast MRV (PC-MRV) is also useful to evaluate the flow state in the dural sinuses but it should be diagnosed carefully whether low visualization of the dural sinus means only functional flow impairment or organized occlusion due to thrombus. To avoid an unnecessary anticoagulant therapy that may worsen epidural hematoma, it is important to recognize the pitfall that PFEDH extending along the sinus groove is easy to misdiagnose for a dural sinus thrombosis.
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A heterozygous loss-of-function mutation of the PTEN gene, one of the tumor suppressor genes, causes a wide variety of disorders, ranging from macrocephaly/autism syndrome to PTEN hamartoma tumor syndrome, including Cowden disease that causes thyroid and breast cancer mainly in the adolescence and young adult generation. An 8-month-old male infant with simple macrocephaly developed a café-au-lait spot and two subcutaneous tumors at the age of 1 year. One of the tumors developed rapidly was resected at the age of 1 year and 9 months and identified as benign lipoma. From the age of 2 years, the patient often threw a tantrum. At the age of 2 years and 9 months, a pathogenic germline mutation was identified in the PTEN gene (NM_000314.7), c.195C>A, p.Y65* in the form of a heterozygous germline variant. Developmental delay was noted but no tumors were found in the thyroid gland and breasts. Immunohistochemistry for PTEN in the resected lipoma demonstrated that the PTEN expression pattern was similar to that in a subcutaneous adipose tissue from a normal subject, suggesting that two-hit was not likely involved in the rapid growth of this lipoma. At the age of 5 years, the patient was diagnosed with autism spectrum disorders with moderate developmental delay. A long-term follow-up is underway to examine developmental changes in psychomotor disorders and possible tumor formation.
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Cluster of differentiation (CD) 166 or activated leukocyte cell adhesion molecule (ALCAM) is a transmembrane molecule known to be an intercellular adhesion factor. The expression and function of ALCAM in medulloblastoma (MB), a pediatric brain tumor with highly advanced molecular genetics, remains unclear. Therefore, this study aimed to clarify the significance and functional role of ALCAM expression in MB. ALCAM expression in 45 patients with MB was evaluated by immunohistochemical analysis of formalin-fixed paraffin-embedded clinical specimens and the relationship between ALCAM expression and pathological type/molecular subgroup, such as WNT, SHH, Group 3, and Group 4, was examined. Eight ALCAM positive (18%), seven partially positive (16%), and 30 negative (67%) cases were detected. All seven cases of the WNT molecular subgroup were ALCAM positive and ALCAM expression strongly correlated with this subgroup (P < 0.0001). In addition, functional studies using MB cell lines revealed ALCAM expression affected proliferation and migration as a positive regulator in vitro. However, ALCAM silencing did not affect survival or the formation of leptomeningeal dissemination in an orthotopic mouse model, but did induce a malignant phenotype with increased tumor cell invasion at the dissemination sites (P = 0.0029). In conclusion, our results revealed that ALCAM exhibited highly specific expression in the WNT subgroup of MB. Furthermore, we demonstrated that the cell kinetics of MB cell lines can be altered by the expression of ALCAM.
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Antígenos CD/metabolismo , Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas Fetales/metabolismo , Meduloblastoma/metabolismo , Proteínas Wnt/metabolismo , Molécula de Adhesión Celular del Leucocito Activado/genética , Adolescente , Animales , Antígenos CD/fisiología , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Adhesión Celular/genética , Moléculas de Adhesión Celular Neuronal/fisiología , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Cerebelosas/genética , Niño , Preescolar , Femenino , Proteínas Fetales/fisiología , Expresión Génica/genética , Perfilación de la Expresión Génica , Humanos , Lactante , Japón/epidemiología , Masculino , Meduloblastoma/fisiopatología , Ratones , Invasividad Neoplásica , ARN Mensajero/genética , Proteínas Wnt/genética , Adulto JovenRESUMEN
We report two cases of aplasia cutis congenita associated with hair collar signs and hemangioma simplex in their parietal regions. A hair collar sign and a hemangioma are known to suggest the possibility of underlying neural tube defects. However, no obvious bone defects or heterotopic neural tissue were observed in the imaging and histopathological examinations. Nevertheless, some pathological observations similar in both cases suggested abnormalities in the process of ectodermal fusion. A flat epidermis and a lack of appendages were recognized. Both cases also exhibited the presence of melanocytes in a portion of the superficial dermal layer. An increase in the number of macrophages was observed in the dermal area with neither elastic fibers nor normal collagen fibers. The peripheral hair follicles grew horizontally.