RESUMO
BACKGROUND: Acalvaria, or acrania, is a rare congenital cranial vault defect with neurocranium absences, including complete or part of calvaria flat bones, dura mater, and associated muscles, but with a still present in the central nervous system, skull base, facial bones, and skin-covered the defect. It is a sporadic incidence without apparent genetic factors confirmed. Acalvaria is often misdiagnosed as anencephaly; the distinguishable difference is that anencephaly has an absence (partial or complete) of the brain tissue, including the skull and scalp. Acalvaria is considered a fatal anomaly with a low survival rate, and only a few cases of extended survival have been reported until now. To the best of the author's knowledge, no acalvaria case has been published in Papua, and only one reported case of the coexistence of acalvaria with schizencephaly in Brazil (2018). CASE REPORT: Herein, we present a case of an indigenous South Papuan living newborn with primary acalvaria and open-lip schizencephaly in a frontoparietal region. A male newborn baby was born from a 39-year-old female Marind-Anim tribe patient with a 38th week of gestation, with no previous history of miscarriage, is not a consanguineous marriage, and had an unremarkable medical history during this pregnancy. Post-natal physical examinations showed an irregularly shaped head with 11.5 cm diameter concave of the right side, with a soft brain-like consistency palpable and the absence of half right frontoparietal calvarium covered with a presence of scalp and hair. Cranial 2-dimension ultrasonography shows an absence of half right frontoparietal calvaria bone with a complete presence of scalp and periosteum covering the defect with a fluid accumulation (anechoic) below the periosteum. A transverse axis view shows a complete structure but hypoplasia of brain cortex with visible slightly dysgenesis of gyrus and sulcus in both hemispheres convincing the acalvaria condition not anencephaly. A fluid accumulation above brain parenchyma of the frontoparietal region happened to be a cerebrospinal fluid coming from a wide-open cleft extending from the left lateral and fourth ventricles to the cerebral cortex, suggesting a typical condition of open-lip schizencephaly. Further health follow-ups until 6 months old showed still normal physical and behavioral development with no sign of complications. CONCLUSIONS: No standard acalvaria treatment is being established; conservative and supportive therapy is mostly taken considering their low survival rate. With the advancement of medical technology nowadays, surgical approaches, including scalp defect closure, bone graft, and 3D-printed defect filling, are being performed and have succeeded in a few cases. Long-term follow-up is required to monitor their neuro-psychological development and complication incidences that need further intervention.
Assuntos
Esquizencefalia , Humanos , Recém-Nascido , Masculino , Esquizencefalia/complicações , Esquizencefalia/genética , Crânio/anormalidades , FemininoRESUMO
The COL4A1 (collagen Type 4 alpha1) pathogenic variant is associated with porencephaly and schizencephaly and accounts for approximately 20% of these patients. This gene variant leads to systemic microvasculopathy, which manifests as brain, ocular, renal, and muscular disorders. However, only a few patients with surgical interventions have been reported and the potential surgical risks are unknown. Here, we present the cases of two female patients between 7 and 8 years of age who were diagnosed with the COL4A1 variant and underwent laparoscopy-assisted percutaneous endoscopic gastrostomy (LAPEG) for oral dysphagia. Their primary brain lesions were caused by porencephaly and paralysis, which are caused by multiple cerebral hemorrhages and infarctions, and both patients had refractory epileptic complications. Although LAPEG was successfully performed in both patients without any intraoperative complications, one patient developed alveolar hemorrhage postoperatively and required mechanical ventilation. Thus, careful perioperative management of patients with the COL4A1 variant is important.
Assuntos
Laparoscopia , Porencefalia , Esquizencefalia , Humanos , Feminino , Gastrostomia/efeitos adversos , Esquizencefalia/genética , Laparoscopia/efeitos adversos , Complicações Intraoperatórias , Colágeno Tipo IV/genéticaRESUMO
OBJECTIVE: To establish the prevalence of COL4A1 and COL4A2 gene mutations in fetuses presenting with a phenotype suggestive of cerebral injury. METHODS: This was a single-center retrospective analysis of all cases of fetal cerebral anomalies suggestive of COL4A1 or COL4A2 gene mutation over the period 2009-2018. Inclusion criteria were: (1) severe and/or multifocal hemorrhagic cerebral lesions; (2) multifocal ischemic-hemorrhagic cerebral lesions. These anomalies could be of different ages and associated with schizencephaly or porencephaly. Between fetuses with and those without a mutation, we compared gestational age at the time of diagnosis, parity and fetal gender. RESULTS: Among the 956 cases of cerebral anomaly diagnosed in our center during the 10-year study period, 18 fetuses were identified for inclusion. A pathogenic COL4A1 gene mutation was found in five of these cases, among which four were de-novo mutations. A variant of unknown significance was found in four fetuses: in the COL4A1 gene in one case and in the COL4A2 gene in three cases. No COL4A1 or COL4A2 mutation was found in the remaining nine fetuses. The median (interquartile range) gestational age at diagnosis was significantly lower in cases with a mutation (24 (22-26) weeks) than in cases without a mutation (32 (29.5-34.5) weeks) (P = 0.03). CONCLUSIONS: A phenotype suggestive of cerebral injury was found in 18 of the 956 (1.9%) cases in our population, in 28% of which there was an associated COL4A1 or COL4A2 mutation. COL4A1 and COL4A2 gene mutations should be sought systematically in cases of severe and/or multifocal hemorrhagic or ischemic-hemorrhagic cerebral lesions, with or without schizencephaly or porencephaly. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Hemorragia Cerebral/embriologia , Hemorragia Cerebral/genética , Colágeno Tipo IV/genética , Malformações do Desenvolvimento Cortical/embriologia , Malformações do Desenvolvimento Cortical/genética , Adulto , Hemorragia Cerebral/diagnóstico , Feminino , Idade Gestacional , Humanos , Malformações do Desenvolvimento Cortical/diagnóstico , Mutação , Fenótipo , Porencefalia/diagnóstico , Porencefalia/embriologia , Porencefalia/genética , Gravidez , Resultado da Gravidez/genética , Diagnóstico Pré-Natal/métodos , Prevalência , Estudos Retrospectivos , Esquizencefalia/diagnóstico , Esquizencefalia/embriologia , Esquizencefalia/genéticaRESUMO
Background: Schizencephaly is a neuronal migration anomaly characterized by presence of a cleft between ependymal layer of the ventricle and pia mater of the cerebral cortex. It may be associated with additional cerebral abnormalities, including polymicrogyria, pachygyria, gray matter heterotopy, ventriculomegaly and corpus callosum agenesis. Case Report: We present a female fetus with schizencephaly accompanied by occipital encephalocele, polymicrogyria, agenesis of the corpus callosum, dysmorphic facies and cardiac muscular ventricular septal defect. Array comparative genomic hybridization (array-cGH) analysis revealed a deletion of chromosome 22q13.32 including FAM19A5 gene that is a member of TAFA family. Conclusions: Schizencephaly may be accompanied by unexpected structural and genetic anomalies as in our case with occipital encephalocele, dysmorphic facies, cardiac ventricular septal defect and chromosome 22q13.32 deletion.
Assuntos
Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 22 , Encefalocele/genética , Esquizencefalia/genética , Agenesia do Corpo Caloso/genética , Hibridização Genômica Comparativa/métodos , Encefalocele/diagnóstico , Feminino , Humanos , Esquizencefalia/diagnóstico , Adulto JovemRESUMO
BACKGROUND: Schizencephaly is a rare congenital central nervous system malformation characterized by linear, thickened clefts of the cerebral mantle. Recently, germline mutations in collagen type IV alpha 1 (COL4A1) have been reported to be a genetic cause of schizencephaly as a result of prenatal stroke. Patients with COL4A1 mutation demonstrate a variety of disease phenotypes. However, little is known about the potential complications of patients with COL4A1 mutations before and after neurologic surgery. CASE DESCRIPTION: A 9-month-old boy with schizencephaly and a congenital cataract underwent a ventriculoperitoneal shunt for progressive hydrocephalus. Postoperatively, he developed malignant hyperthermia and cerebral venous thrombosis. Early treatment with dantrolene sodium and hydration was effective. Genetic testing revealed a germline COL4A1 mutation. CONCLUSIONS: To our knowledge, malignant hyperthermia and cerebral venous thrombosis have not been reported in the literature in patients with COL4A1 mutations after surgery. Schizencephaly arising from COL4A1 mutations might be a disease prone to these adverse effects because this mutation is known to be associated with venous tortuosity, venous vulnerability, and muscle spasms due to basement membrane protein abnormalities. We need to better understand the wide spectrum of clinical phenotypes of COL4A1 mutations and potential complications in order to better manage surgery of patients with schizencephaly.
Assuntos
Colágeno Tipo IV/genética , Mutação em Linhagem Germinativa/genética , Hipertermia Maligna/etiologia , Esquizencefalia/genética , Trombose dos Seios Intracranianos/etiologia , Derivação Ventriculoperitoneal/efeitos adversos , Dantroleno/uso terapêutico , Hidratação/métodos , Humanos , Hidrocefalia/tratamento farmacológico , Hidrocefalia/cirurgia , Lactente , Masculino , Relaxantes Musculares Centrais/uso terapêutico , Complicações Pós-Operatórias/etiologia , Trombose dos Seios Intracranianos/tratamento farmacológicoRESUMO
Mutations in COL4A1 have been reported in schizencephaly and porencephaly combined with microbleeds or calcifications, often associated with ocular and renal abnormalities, myopathy, elevated creatine kinase levels and haemolytic anaemia. In this study, we aimed to clarify the phenotypic spectrum of COL4A1/A2 mutations in the context of cortical malformations that include schizencephaly, polymicrogyria and/or heterotopia. METHODS: We screened for COL4A1/A2 mutations in 9 patients with schizencephaly and/or polymicrogyria suspected to be caused by vascular disruption and leading to a cerebral haemorrhagic ischaemic event. These included 6 cases with asymmetrical or unilateral schizencephaly and/or polymicrogyria and 3 cases with bilateral schizencephaly. RESULTS: One de novo missense COL4A1 mutation (c.3715â¯Gâ¯>â¯A, p.(Gly1239Arg)) and two COL4A2 mutations were found, respectively in one familial case (c.4129G > A, p.(Gly1377Arg)) and one sporadic patient (c.1776+1G > A). In three other cases, COL4A1 variants of unknown significance were identified. None of our patients demonstrated neuromuscular or hematological anomalies. Brain malformations included a combination of schizencephaly, mainly asymmetrical, with porencephaly or ventriculomegaly (3/3 mutated patients). We did not observe microbleeds or microcalcifications in any of our cases, hence we do not believe that they represent a distinctive feature of COL4A1/A2 mutations. CONCLUSIONS: Our study further emphasizes the need to search for both COL4A1 and COL4A2 mutations in children presenting with uni- or bilateral polymicrogyria with schizencephaly, even in the absence of intracranial microbleeds, calcification or associated systemic features.
Assuntos
Colágeno Tipo IV/genética , Polimicrogiria/genética , Porencefalia/genética , Esquizencefalia/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Mutação , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/fisiopatologia , Porencefalia/diagnóstico por imagem , Porencefalia/fisiopatologia , Esquizencefalia/diagnóstico por imagem , Esquizencefalia/fisiopatologiaRESUMO
Patients with COL4A1 mutation-related disorders demonstrate a variety of disease phenotypes, which caused by small-vessel dysfunction in the brain, eyes, kidney, muscle, or heart. The involvement of organs mainly depends on the expression of the COL4A1 gene. Complication or dysfunction of the alveolar tissue has not been reported in the literature on COL4A1 mutation-related disorders. We herein report the case of a boy with schizencephaly, renovascular hypertension, and retinal arteriosclerosis of unknown origin, who suffered from severe and repetitive alveolar hemorrhage at 9 years of age. A novel COL4A1 mutation was finally identified as the genetic cause. The pulmonary complication in the present case represents an important pathophysiological mechanism COL4A1 mutation-related disorders; lung tissue with COL4A1 gene mutations may be vulnerable and environmental substances and microorganisms in the air could accumulate to cause chronic damage in the alveolar tissues, especially in patients with tracheostoma and renovascular hypertension.
Assuntos
Arteriosclerose/genética , Colágeno Tipo IV/genética , Hemorragia/genética , Hemorragia/patologia , Hipertensão Renovascular/genética , Alvéolos Pulmonares/patologia , Esquizencefalia/genética , Criança , Predisposição Genética para Doença , Hemorragia/mortalidade , Humanos , MasculinoRESUMO
BACKGROUND: A clinical case is described of growth retardation, severe developmental delay, facial dysmorphic features with microcephaly, as well as congenital cataract, schizencephaly, periventricular calcifications, and epilepsy. METHODS: TORCH infection was suspected, but all tests for toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus were negative for the child and her mother; however, an increased level of antibodies against parvovirus B19 was detected in the proband. RESULTS: Chromosomal analysis and array-CGH showed no aberration. Target capture sequencing for COL4A1 and COL4A2 revealed a de novo COL4A1 mutation (c.2123G>T [p.Gly708Val]). The mutation occurred at a highly conserved Gly residue in the Gly-X-Y repeat of the collagen triple helical domain, suggesting that these mutations may alter the collagen IV α1α1α2 heterotrimers. The mutation was predicted to be damaging. CONCLUSION: We suggest that COL4A1 testing should be considered in patients with schizencephaly as well as with phenotype suggesting TORCH infection without any proven etiological factors.