RESUMO
OBJECTIVE: The aim of this study was to provide a full characterization of a cohort of 11 pediatric patients diagnosed with PTEN hamartoma tumor syndrome (PHTS). PATIENTS AND METHODS: Eleven patients with genetic diagnostic of PHTS were recruited between February 2019 and April 2023. Clinical, imaging, demographic, and genetic data were retrospectively collected from their hospital medical history. RESULTS: Regarding clinical manifestations, macrocephaly was the leading sign, present in all patients. Frontal bossing was the most frequent dysmorphism. Neurological issues were present in most patients. Dental malformations were described for the first time, being present in 27% of the patients. Brain MRI showed anomalies in 57% of the patients. No tumoral lesions were present at the time of the study. Regarding genetics, 72% of the alterations were in the tensin-type C2 domain of PTEN protein. We identified four PTEN genetic alterations for the first time. CONCLUSIONS: PTEN mutations appear with a wide variety of clinical signs and symptoms, sometimes associated with phenotypes which do not fit classical clinical diagnostic criteria for PHTS. We recommend carrying out a genetic study to establish an early diagnosis in children with significant macrocephaly. This facilitates personalized monitoring and enables anticipation of potential PHTS-related complications.
Assuntos
Síndrome do Hamartoma Múltiplo , PTEN Fosfo-Hidrolase , Humanos , Feminino , Masculino , PTEN Fosfo-Hidrolase/genética , Criança , Síndrome do Hamartoma Múltiplo/genética , Síndrome do Hamartoma Múltiplo/diagnóstico por imagem , Pré-Escolar , Adolescente , Estudos Retrospectivos , Lactente , Mutação/genética , Megalencefalia/genética , Megalencefalia/diagnóstico por imagemRESUMO
Abusive head trauma (AHT) is a significant cause of morbidity and mortality for infants. Determining when to pursue a complete physical abuse evaluation can be difficult, especially for nonspecific findings or when a child appears clinically well. This retrospective study of 7 cases sought to describe the presentation, evaluation, and diagnoses for infants with abnormal subdural collections identified on cranial ultrasound for macrocephaly, and to determine how frequently AHT is diagnosed. The results of this study showed that while each patient presented due to asymptomatic macrocephaly, the extent of the workup varied greatly. In addition, no infants had suspicious injuries for abuse during the initial evaluation or the year following. In summary, among the 7 patients seen for asymptomatic macrocephaly with possible subdural hemorrhage, there were very inconsistent child abuse workups. There needs to be a standardized clinical guideline for this specific patient population involving a child abuse pediatric evaluation.
Assuntos
Maus-Tratos Infantis , Traumatismos Craniocerebrais , Megalencefalia , Lactente , Criança , Humanos , Estudos Retrospectivos , Hematoma Subdural/diagnóstico por imagem , Hematoma Subdural/etiologia , Traumatismos Craniocerebrais/diagnóstico por imagem , Maus-Tratos Infantis/diagnóstico , Megalencefalia/diagnóstico por imagem , Megalencefalia/complicaçõesRESUMO
The syndrome of megalencephaly, mega corpus callosum (MEG-MegaCC) accompanied by complete lack of motor development is a rare condition with only few sporadic cases having been reported in the literature. In this paper, we describe a child from non-consanguineous parents presenting with MegaCC, psychomotor retardation, and language impairment linked to MEG-MegaCC syndrome. Genetic analysis, radiological findings, and detailed neurological phenotype of MEG-MegaCC syndrome with its overlapping syndromes would allow for a better classification of the disease spectrum.
Assuntos
Megalencefalia , Malformações do Sistema Nervoso , Criança , Humanos , Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/complicações , Agenesia do Corpo Caloso/diagnóstico por imagem , Megalencefalia/complicações , Megalencefalia/diagnóstico por imagem , SíndromeRESUMO
INTRODUCTION: The subarachnoid space (SAS) is a potential space surrounding the brain where the cerebrospinal fluid (CSF) flows. Previous work demonstrated how the SAS width changes during pregnancy and measured the normal values per gestational week. OBJECTIVES: Studying the ratio between the fetal brain volume (STV) and the SAS width (SS ratio), as measured via fetal magnetic resonance imaging (MRI) in different fetal pathologies - macrocephaly and microcephaly, and studying the correlation between this ratio and the gestational week. METHODS: A retrospective study was conducted on 77 fetuses that underwent fetal MRI scans during gestational weeks 29-37, in three groups: 23 normocephaly, 27 macrocephaly, and 27 microcephaly. SAS width was measured in 10 points via fetal MRI scans, and a ratio was calculated between the width and STV. RESULTS: The SS ratio is largest in microcephaly group and smallest in normocephaly group, with the macrocephaly group between them. All comparisons were statistically significant except between the macrocephaly and normocephaly groups. There was a strong positive correlation between SS ratio and week of gestation. CONCLUSIONS: The SS ratio is statistically different between normocephalic fetuses and fetuses with macrocephaly or microcephaly. From week 29 this ratio enlarges with gestational age. DISCUSSION: The SAS affects the fetal head circumference, an important parameter of fetal growth, thus we decided to study the SS ratio in pathologies of the head circumference. Previous work demonstrated how the STV and the SAS width expand starting at a specific gestational age, thus the gestational week also affects the SS ratio. Summary: The SS ratio is affected by pathologies of the fetal head circumference and by gestational age.
Assuntos
Megalencefalia , Microcefalia , Gravidez , Feminino , Humanos , Microcefalia/diagnóstico por imagem , Estudos Retrospectivos , Feto/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Idade Gestacional , Espaço Subaracnóideo/diagnóstico por imagem , Megalencefalia/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodosRESUMO
BACKGROUND: Macrocephaly is present in 2.3% of children with important neurosurgical conditions in the differential diagnosis. The objective of this study was to identify clinical associations with actionable imaging findings among children with head imaging for macrocephaly. METHODS: We conducted a case-control study of head imaging studies ordered for macrocephaly among children 24 months and younger in a multistate children's health system. Four neurosurgeons reviewed the images, determining cases to be a 'concern' if neurosurgical follow-up or intervention was indicated. Electronic health records were reviewed to collect patient-level data and to determine if surgery was performed. Controls were matched 3:1 to cases of 'concern' in a multivariate model using conditional logistic regression. RESULTS: In the study sample (n = 1293), 46 (4%) were concern cases, with 15 (1%) requiring surgery. Significant clinical factors associated with neurosurgical concern were bulging fontanel [aOR 7.47, (95% CI: 2.28-24.44), P < 0.001], prematurity [aOR 21.26, (95% CI: 3.76-120.21), P < 0.001], any delay [aOR 2.67, (95% CI: 1.13-6.27), P = 0.03], and head-weight Z-score difference (W_diff, defined as the difference between the Z-scores of head circumference and weight) [aOR 1.70, (95% CI: 1.22-2.37), P = 0.002]. CONCLUSIONS: Head imaging for macrocephaly identified few patients with findings of concern and fewer requiring surgery. A greater head-weight Z-score difference appears to represent a novel risk factor for neurosurgical follow-up or intervention.
Assuntos
Megalencefalia , Humanos , Criança , Pré-Escolar , Estudos de Casos e Controles , Megalencefalia/diagnóstico por imagem , Megalencefalia/cirurgia , Tomografia Computadorizada por Raios X , Fatores de Risco , CefalometriaRESUMO
BACKGROUND: Inactivating mutations in PTEN are among the most common causes of megalencephaly. Activating mutations in other nodes of the PI3K/AKT/MTOR signaling pathway are recognized as a frequent cause of cortical brain malformations. Only recently has PTEN been associated with cortical malformations, and analyses of their prognostic significance have been limited. METHODS: Retrospective neuroimaging analysis and detailed chart review were conducted on 20 participants identified with pathogenic or likely pathogenic mutations in PTEN and a cortical brain malformation present on brain magnetic resonance imaging. RESULTS: Neuroimaging analysis revealed four main cerebral phenotypes-hemimegalencephaly, focal cortical dysplasia, polymicrogyria (PMG), and a less severe category, termed "macrocephaly with complicated gyral pattern" (MCG). Although a high proportion of participants (90%) had neurodevelopmental findings on presentation, outcomes varied and were favorable in over half of participants. Consistent with prior work, 39% of participants had autism spectrum disorder and 19% of participants with either pure-PMG or pure-MCG phenotypes had epilepsy. Megalencephaly and systemic overgrowth were common, but other systemic features of PTEN-hamartoma tumor syndrome were absent in over one-third of participants. CONCLUSIONS: A spectrum of cortical dysplasias is present in individuals with inactivating mutations in PTEN. Future studies are needed to clarify the prognostic significance of each cerebral phenotype, but overall, we conclude that despite a high burden of neurodevelopmental disease, long-term outcomes may be favorable. Germline testing for PTEN mutations should be considered in cases of megalencephaly and cortical brain malformations even in the absence of other findings, including cognitive impairment.
Assuntos
Transtorno do Espectro Autista , Megalencefalia , Polimicrogiria , Humanos , Fosfatidilinositol 3-Quinases , Estudos Retrospectivos , Megalencefalia/diagnóstico por imagem , Megalencefalia/genética , Encéfalo , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/genética , PTEN Fosfo-Hidrolase/genéticaAssuntos
Megalencefalia , Feminino , Gravidez , Humanos , Síndrome , Megalencefalia/diagnóstico por imagemRESUMO
BACKGROUND: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation. The MLC1 protein plays a role in astrocyte activation during neuroinflammation and regulates volume decrease following astrocyte osmotic swelling. Loss of MLC1 function activates interleukin (IL)-1ß-induced inflammatory signals. Theoretically, IL-1 antagonists (such as anakinra and canakinumab) can slow the progression of MLC. Herein, we present two boys from different families who had MLC due to biallelic MLC1 gene mutations and were treated with the anti-IL-1 drug anakinra. METHODS: Two boys from different families presented with megalencephaly and psychomotor retardation. Brain magnetic resonance imaging findings in both patients were compatible with the diagnosis of MLC. The diagnosis of MLC was confirmed via Sanger analysis of the MLC1 gene. Anakinra was administered to both patients. Volumetric brain studies and psychometric evaluations were performed before and after anakinra treatment. RESULTS: After anakinra therapy, brain volume in both patients decreased significantly and cognitive functions and social interactions improved. No adverse effects were observed during anakinra therapy. CONCLUSIONS: Anakinra or other IL-1 antagonists can be used to suppress disease activity in patients with MLC; however, the present findings need to be confirmed via additional research.
Assuntos
Proteína Antagonista do Receptor de Interleucina 1 , Megalencefalia , Proteínas de Membrana , Receptores de Interleucina-1 , Humanos , Masculino , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Cognição , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Megalencefalia/diagnóstico por imagem , Megalencefalia/tratamento farmacológico , Megalencefalia/genética , Proteínas de Membrana/genética , Mutação , Receptores de Interleucina-1/antagonistas & inibidoresRESUMO
BACKGROUND: Severe macrocephaly can still be found in developing countries. This condition is usually caused by neglected hydrocephalus and can cause a lot of morbidities. Cranial vault reconstruction cranioplasty is the main treatment option for severe macrocephaly. Holoprosencephaly is often seen with features of microcephaly. Hydrocephalus should be considered as the main cause in HPE patients with features of macrocephaly. In this report, we present a rare case of cranial vault reduction cranioplasty procedure in patient with severe macrocephaly due to holoprosencephaly and subdural hygroma. CASE DESCRIPTION: A 4-year-10-month-old Indonesian boy was admitted with head enlargement since birth. He had a history of VP shunt placement when he was 3 months old. But the condition was neglected. Preoperative head CT showed massive bilateral subdural hygroma that compressed brain parenchyma caudally. From the craniometric calculation, the occipital frontal circumference was 70.5 cm with prominent vertex expansion, the distance between nasion to inion was 11.91 cm and the vertical height was 25.59 cm. The preoperative cranial volume was 24.611 cc. The patient underwent subdural hygroma evacuation and cranial vault reduction cranioplasty. The postoperative cranial volume was 10.468 cc. CONCLUSION: Subdural hygroma can be a rare cause of severe macrocephaly in holoprosencephaly patients. Cranial vault reduction cranioplasty and subdural hygroma evacuation is still the main treatment option. Our procedure successfully reduces significant cranial volume (57.46% volume reduction).
Assuntos
Holoprosencefalia , Hidrocefalia , Megalencefalia , Derrame Subdural , Masculino , Humanos , Lactente , Holoprosencefalia/complicações , Derrame Subdural/etiologia , Crânio/diagnóstico por imagem , Crânio/cirurgia , Megalencefalia/complicações , Megalencefalia/diagnóstico por imagem , Megalencefalia/cirurgia , Hidrocefalia/cirurgiaRESUMO
Macrocephaly, defined as a head circumference greater than 2 standard deviations above the mean, is a relatively common presenting symptom in the pediatric population at routine well-child examinations and a common indication for neuroimaging. Multiple imaging modalities are complementary in evaluating macrocephaly, including US, CT, and MRI. The differential diagnosis for macrocephaly is broad, and many disease processes lead to macrocephaly only when the sutures are open. In patients with closed sutures, these entities instead lead to increased intracranial pressure, according to the Monroe-Kellie hypothesis, which states that there is an equilibrium between intracranial constituents due to the fixed intracranial volume. The authors describe a useful paradigm for classifying macrocephaly by identifying which of the four components of the cranium (ie, cerebrospinal fluid, blood and vasculature, brain parenchyma, or calvarium) has an increased volume. Patient age, additional imaging findings, and clinical symptoms are also useful features. Most cases in the pediatric population are due to increased cerebrospinal fluid spaces, such as benign enlargement of the subarachnoid space, which must be carefully distinguished from subdural fluid collections in patients with accidental or nonaccidental trauma. Other common causes of macrocephaly are discussed, including hydrocephalus secondary to an aqueductal web, hemorrhage, or a neoplasm. The authors also provide information on some of the rarer diseases for which imaging may provide the impetus for genetic testing (eg, overgrowth syndromes and metabolic disorders). ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.
Assuntos
Megalencefalia , Criança , Humanos , Lactente , Megalencefalia/diagnóstico por imagem , Megalencefalia/epidemiologia , Cabeça , Encéfalo , Espaço Subaracnóideo , Imageamento por Ressonância MagnéticaRESUMO
Hemimegalencephaly (HME) is a rare neurological diagnosis defined as hamartomatous overgrowth of one cerebral hemisphere. The hypothesised pathogenesis is due to an increased number or size of neural cells; however, the exact mechanism can vary widely, depending on the underlying aetiology. We report a case outlining the prenatal diagnostic process and obstetric considerations for delivering an infant with HME secondary to megalencephaly-capillary malformation syndrome. After diagnosis, our patient was induced and delivered at 37 weeks of gestation via operative vaginal delivery. To our knowledge, this is the first report describing the course from prenatal diagnosis through delivery of a fetus with HME.
Assuntos
Megalencefalia , Dermatopatias Vasculares , Telangiectasia , Gravidez , Lactente , Feminino , Humanos , Megalencefalia/diagnóstico por imagem , Megalencefalia/complicações , Dermatopatias Vasculares/complicações , Telangiectasia/complicações , Diagnóstico Pré-NatalRESUMO
Macrocephaly is a common diagnosis in the pediatric population, particularly in the infantile time period. There is a wide range of causes of macrocephaly, from benign to malignant, for which imaging plays a key role in the diagnosis and clinical guidance. Our aim is to review the distinct and prevalent neuroimaging findings in the evaluation of the macrocephalic infant.
Assuntos
Megalencefalia , Criança , Humanos , Lactente , Megalencefalia/diagnóstico por imagem , NeuroimagemRESUMO
OBJECTIVE: Benign Enlargement of the Subarachnoid Spaces in Infancy (BESSI) is a common finding during workup for progressive macrocephaly. BESSI has been associated with slightly higher prevalence of subdural (SD) spaces and a risk for developing subdural hematoma. This study utilizes fast brain magnetic resonance imaging (MRI) to investigate the prevalence of visible SD spaces in BESSI. METHODS: A retrospective review was performed for all pediatric patients who underwent brain MRI for macrocephaly. Patients with a diagnosis of BESSI were included in the study. A total of 109 patients met the inclusion criteria. Patient demographics were collected, and images were reviewed for size of subarachnoid, visible SD spaces, and ventricle size. Descriptive and inferential statistics were performed. RESULTS: The average age was 8 ± 4.6 months, 64 (59%) were male, and 55 patients had no previous medical history (50%). Sixty-seven percent of all patients were identified to have visible SD spaces. Eleven patients had confirmed SD hematomas; 1 patient was deemed to have abusive head trauma. Visible SD spaces were associated with younger age (6.9 months). Thirty-one patients with visible SD spaces had follow-up MRI, with complete resolution by 33 months. CONCLUSIONS: BESSI is a self-limiting pathology that has been associated with visible SD spaces and potential risk for SD hemorrhages. We report a high prevalence of visible SD spaces within BESSI through utilization of fast brain MRI. These spaces may contribute to the higher rate of incidental subdural hematoma in this population.
Assuntos
Megalencefalia , Espaço Subdural , Criança , Feminino , Hematoma Subdural/epidemiologia , Humanos , Hipertrofia/patologia , Lactente , Imageamento por Ressonância Magnética , Masculino , Megalencefalia/diagnóstico por imagem , Megalencefalia/epidemiologia , Megalencefalia/patologia , Prevalência , Estudos Retrospectivos , Espaço Subaracnóideo/diagnóstico por imagem , Espaço Subaracnóideo/patologia , Espaço Subdural/patologiaRESUMO
Macrocephaly is a clinical term defined as an occipitofrontal circumference more than two standard deviations above the mean. It is present in 5% of children and is a common indication for imaging studies. There are multiple causes of macrocephaly; most of them are benign. Nevertheless, in some cases, macrocephaly is the clinical manifestation of a condition that requires timely medical and/or surgical treatment. The importance of imaging studies lies in identifying the patients who would benefit from treatment. Children with macrocephaly associated with neurologic alterations, neurocutaneous stigmata, delayed development, or rapid increase of the circumference have a greater risk of having disease. By contrast, parental macrocephaly is predictive of a benign condition. Limiting imaging studies to patients with increased risk makes it possible to optimize resources and reduce unnecessary exposure to tests.
Assuntos
Megalencefalia , Criança , Humanos , Imageamento por Ressonância Magnética/métodos , Megalencefalia/diagnóstico por imagemRESUMO
Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a rare disorder that arises as a result of a somatic mosaic mutation in the PIK3CA gene. It characteristically presents with postnatal or congenital megalencephaly, cutaneous capillary malformations, postaxial polydactyly and often segmental or focal body overgrowth. We report a 7-year-old boy with known MCAP who was diagnosed at around 10 months old with a mosaic change in the PIK3CA gene. He was found to have hall-mark clinical signs; macrocephaly and four-limb postaxial polydactyly. Since diagnosis, he has had multiple clinical features, most of which typically present in children with MCAP. He has now been diagnosed with autism spectrum disorder (ASD), demand avoidance and is under assessment for attention deficit hyperactivity disorder. Although some cases have been raised to the M-CM Network, to our knowledge this is the first case of ASD in MCAP to be reported in the literature.
Assuntos
Transtorno do Espectro Autista , Megalencefalia , Polimicrogiria , Transtorno do Espectro Autista/genética , Capilares/anormalidades , Criança , Humanos , Lactente , Masculino , Megalencefalia/diagnóstico por imagem , Megalencefalia/genética , Mutação , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/genética , Malformações VascularesRESUMO
Bachmann-Bupp syndrome (BABS) is a rare syndrome caused by gain-of-function variants in the C-terminus of ornithine decarboxylase (ODC coded by the ODC1 gene). BABS is characterized by developmental delay, macrocephaly, macrosomia, and an unusual pattern of non-congenital alopecia. Recent diagnosis of four more BABS patients provides further characterization of the phenotype of this syndrome including late-onset seizures in the oldest reported patient at 23 years of age, representing the first report for this phenotype in BABS. Neuroimaging abnormalities continue to be an inconsistent feature of the syndrome. This may be related to the yet unknown impact of ODC/polyamine dysregulation on the developing brain in this syndrome. Variants continue to cluster, providing support to a universal biochemical mechanism related to elevated ODC protein, enzyme activity, and abnormalities in polyamine levels. Recommendations for medical management can now be suggested as well as the potential for targeted molecular or metabolic testing when encountering this unique phenotype. The natural history of this syndrome will evolve with difluoromethylornithine (DFMO) therapy and raise new questions for further study and understanding.
Assuntos
Alopecia/genética , Deficiências do Desenvolvimento/genética , Transportadores de Ácidos Dicarboxílicos/genética , Megalencefalia/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Adolescente , Adulto , Alopecia/diagnóstico , Alopecia/tratamento farmacológico , Alopecia/patologia , Encéfalo/anormalidades , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Criança , Pré-Escolar , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/diagnóstico por imagem , Deficiências do Desenvolvimento/tratamento farmacológico , Eflornitina/uso terapêutico , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Megalencefalia/diagnóstico por imagem , Megalencefalia/tratamento farmacológico , Megalencefalia/patologia , Neuroimagem , Fenótipo , Poliaminas/metabolismo , Convulsões/diagnóstico , Convulsões/tratamento farmacológico , Convulsões/genética , Convulsões/patologia , Adulto JovemRESUMO
KCNT2 variants resulting in substitutions affecting the Arg190 residue have been shown to cause epileptic encephalopathy and a recognizable facial gestalt. We report two additional individuals with intellectual disability, dysmorphic features, hypertrichosis, macrocephaly and the same de novo KCNT2 missense variants affecting the Arg190 residue as previously described. Notably, neither patient has epilepsy. Homology modeling of these missense variants revealed that they are likely to disrupt the stabilization of a closed channel conformation of KCNT2 resulting in a constitutively open state. This is the first report of pathogenic variants in KCNT2 causing a developmental phenotype without epilepsy.
Assuntos
Epilepsia/genética , Hipertricose/genética , Deficiência Intelectual/genética , Megalencefalia/genética , Canais de Potássio Ativados por Sódio/genética , Adolescente , Arginina/genética , Criança , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/patologia , Feminino , Predisposição Genética para Doença , Humanos , Hipertricose/diagnóstico , Hipertricose/diagnóstico por imagem , Hipertricose/patologia , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/patologia , Megalencefalia/diagnóstico por imagem , Megalencefalia/patologia , Anormalidades Musculoesqueléticas/genética , Anormalidades Musculoesqueléticas/patologia , Mutação de Sentido Incorreto/genética , FenótipoRESUMO
We present the prenatal imaging and whole exomics sequencing with the newly described Snijders Blok-Campeau macrocephaly syndrome.
Assuntos
Megalencefalia , Diagnóstico Pré-Natal , Feminino , Feto/diagnóstico por imagem , Humanos , Megalencefalia/diagnóstico por imagem , Megalencefalia/genética , Gravidez , Ultrassonografia Pré-Natal , Sequenciamento do ExomaRESUMO
Enlarged subarachnoid spaces are a common finding in infants and young children imaged for macrocephaly or an enlarging head circumference, and benign enlargement of the subarachnoid spaces is often diagnosed. Infrequently, presumed "spontaneous" subdural hemorrhages or subdural collections might complicate these enlarged subarachnoid spaces. Children with large bilateral subdural collections might also present for imaging with macrocephaly. Each scenario potentially raises concerns for prior injury because subdural hemorrhage is a frequent finding in children with abusive head trauma.