RESUMO
Importance: Neurocutaneous disorders have significant implications for care of the pregnant patient. As neurocutaneous disorders are uncommon, obstetricians may be unfamiliar with these disorders and with recommendations for appropriate care of this population. Objective: This review aims to summarize existing literature on the interaction between neurocutaneous disorders and pregnancy and to provide a guide for physicians caring for an affected patient. Evidence Acquisition: A PubMed, MEDLINE, and Google Scholar search was carried out with a broad range of combinations of the medical subject headings (MeSH) terms "pregnancy," "Sturge -Weber," "Neurofibromatosis Type 1," "neurofibromatosis type 2," "von Hippel Lindau," "Tuberous Sclerosis," "neurocutaneous disorder," "treatment," "congenital malformations," "neurodevelopmental defects," "miscarriage," "breastfeeding," "autoimmune," "pathophysiology," and "management." References of included articles were searched to identify any articles that may have been missed after the above method was used. Results: Neurocutaneous disorders are associated with increased pregnancy-associated maternal and fetal/neonatal morbidity, largely surrounding hypertensive disorders, epilepsy, and medication exposure. Some features of neurocutaneous disorders may be worsened or accelerated by pregnancy. Neurocutaneous disorders can often be diagnosed prenatally. Therefore, directed assessment should be offered to affected individuals with a personal or family history of a neurocutaneous disorder. Conclusion and Relevance: Patients affected by neurocutaneous disorders who are pregnant or planning for future pregnancy should be carefully followed by a multidisciplinary team, which could include maternal-fetal medicine, neurology, and anesthesia, as well as other relevant subspecialists. Additional research is required regarding optimal counseling and management of these patients.
Assuntos
Síndromes Neurocutâneas , Neurofibromatose 1 , Esclerose Tuberosa , Doença de von Hippel-Lindau , Recém-Nascido , Humanos , Gravidez , Feminino , Síndromes Neurocutâneas/diagnóstico , Síndromes Neurocutâneas/terapia , Síndromes Neurocutâneas/complicações , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnóstico , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico , Neurofibromatose 1/complicaçõesRESUMO
BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder caused by pathogenic variants in VHL gene. The common manifestations include hemangioblastomas (HB) of the central nervous system (CNS) and retina (RH); pheochromocytoma (PHEO); clear cell renal cell carcinoma (ccRCC); pancreatic and renal cysts (PRC) and pancreatic neuroendocrine neoplasm (PNEN). METHODS: The first characterization of VHL in Brazil was published in 2003 and included 20 families with a history of VHL. The aim of this study was to expand the previous Brazilian cohort to include more families, as well as to collect prospectively both clinical and molecular characteristics of patients with VHL to build the VHL Brazilian Registry (VHLBR). Patients with VHL were selected through review of data from medical records of experts and from social networks of support for families with VHL in Brazil. RESULTS: A total of 142 subjects representing 62 unrelated Brazilian families with VHL were registered. The mean age of VHL onset was 28.78 years old and 128 individuals (90.1%) had at least one VHL-related lesion. CNS HB was the most common manifestation occurring in 91 (71%) patients, followed by multiple PRC (48.4%), RH (39.8%), ccRCC (28.9%), PHEO (12.5%) and PNEN (7.8%). Of the 97 subjects whose presence of VHL variants was confirmed, 51 (52.6%) had missense variants, 22 (22.7%) large deletions, 10 (10.3%) frameshift, 7 (7.2%) splice site, 4 (4.1%) nonsense and 3 (3.1%) in-frame deletions. Regarding surveillance, 115 (81%) participants had at least one physician responsible for their outpatient follow-up; however, 69 (60%) of them did not report a regular frequency of tests. CONCLUSION: We built the largest prospective VHLBR with organized collections of clinical and genetic data from families with VHL, which will be helpful to guide policies for VHL care and oncogenetics in Brazil. Although there have been improvements in diagnosis and clinical screening methods, VHL care in Brazil is still deficient, especially regarding surveillance and regular medical appointments with experts.
Assuntos
Carcinoma de Células Renais , Hemangioblastoma , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Adulto , Doença de von Hippel-Lindau/epidemiologia , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/diagnóstico , Brasil/epidemiologia , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Estudos Prospectivos , Neoplasias Renais/genéticaRESUMO
BACKGROUND: Patients with familial erythrocytosis type 2 have no increased risk of von Hippel-Lindau-associated tumors, although mutations in the VHL gene cause both pathologies. CASE REPORT: We present a case of a compound heterozygote patient with von Hippel-Lindau disease and familial erythrocytosis type 2. One of the mutations found in our patient, c.416C>G (p.Ser139Cys) of the VHL gene, has not been previously reported. This case is the second one reported where von Hippel-Lindau disease and familial erythrocytosis type 2 coexist in the same individual. CONCLUSIONS: Despite the low frequency of familial erythrocytosis type 2 in patients with von Hippel-Lindau disease, the possibility of this diagnosis should be considered to avoid unnecessary invasive studies to explain the polyglobulia in these patients and guarantee an adequate follow-up and vigilance of both diseases.
Assuntos
Policitemia , Doença de von Hippel-Lindau , Criança , Humanos , Mutação , Policitemia/congênito , Policitemia/diagnóstico , Policitemia/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/genéticaAssuntos
Neoplasias Cerebelares/etiologia , Hemangioblastoma/etiologia , Cisto Pancreático/etiologia , Doença de von Hippel-Lindau/complicações , Neoplasias Cerebelares/diagnóstico , Criança , Feminino , Hemangioblastoma/diagnóstico , Humanos , Cisto Pancreático/diagnóstico , Doença de von Hippel-Lindau/diagnósticoRESUMO
Hemangioblastoma of the central nervous system occurs as sporadic tumors or as a part of von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary tumor syndrome caused by a germline mutation in the VHL tumor suppressor gene. We screened a Chinese family with VHL for mutations in the VHL gene and evaluated a genetic test for diagnosing VHL disease and clinical screening of family members. DNA extracted from the peripheral blood of all live members and from tissue of deceased family members with VHL disease was amplified by polymerase chain reaction to 3 VHL gene exons. Mutations in the amplification products were compared against the Human Gene Mutation Database. The involvement of multiple organs among the kindred with VHL disease was confirmed by medical history and radiography. Of the 12 members of the 4-generation family, 5 were diagnosed with VHL disease. Patient age at the initial diagnosis was 26-36 years (mean = 31 years). The mean time was 15 (11-19 months) from symptom appearance to the first patient visit to the hospital. Sequence analysis revealed that the frameshift mutation 327del C (p.Gly39Alafs*26) in exon 1 affected all family members, but not the healthy individuals or 16 unrelated controls. Members without gene mutation showed no clinical manifestation of VHL disease. We detected a conserved novel frameshift mutation in the VHL gene of the family members that contributes to VHL. DNA analysis of VHL is advantageous for VHL diagnosis. We developed a quick and reliable method for VHL diagnosis.
Assuntos
Mutação da Fase de Leitura , Hemangioblastoma/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Adulto , Análise Mutacional de DNA , Feminino , Testes Genéticos , Hemangioblastoma/diagnóstico , Hemangioblastoma/etiologia , Humanos , Masculino , Linhagem , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/diagnósticoRESUMO
BACKGROUND: von Hippel-Lindau (VHL) disease is an autosomal dominant and familial multisystemic syndrome that is caused by the inactivation of the VHL gene and it is characterized by diverse types of high vasculated tumours of benign and malign nature. In this work we describe the clinical characteristics and the prenatal diagnosis of a woman with VHL. OBJECTIVE: Describe the first exclusion prenatal case by DNA analysis of the VHL syndrome in Latinoamerican population. MATERIAL AND METHODS: Analysis of a Mexican familial pedigree showed 5 affected subjects with VHL on 3 consecutive generations. The proband was a 7 weeks pregnancy woman who was referred to our service for familiar and personal history of this disease. Maternal DNA was obtained from peripheral blood leukocytes, while fetal DNA was isolated from amniotic liquid cells on the 15th week. The maternal and fetal DNA analysis were done by the Polymerase Chain reaction (PCR) and the direct nucleotide sequence of the VHL gene. RESULTS: A novel mutation (c. 161_168 dup GGAGGCCG) in the VHL gene was identified in maternal DNA. Fetal DNA analysis indicated that the fetus inherited the wild-type allele from the mother. CONCLUSION: A novel VHL gene mutation was identified in a familial case of the disease, expanding the mutational spectrum in this disorder. The molecular prenatal testing in the affected woman at 15 weeks of gestation, demonstrated that the fetus did nor inherited the mutated allele. To the best of our knowledge, this is the first example of prenatal-molecular exclusion on VHL syndrome in Latinoamerica population.
Assuntos
Diagnóstico Pré-Natal/métodos , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/diagnóstico , Alelos , Sequência de Bases , DNA/genética , Feminino , Humanos , México , Mutação , Linhagem , Reação em Cadeia da Polimerase , Gravidez , Adulto Jovem , Doença de von Hippel-Lindau/genéticaRESUMO
Von Hippel-Lindau syndrome is an autosomal dominant and familial multisystemic syndrome that is caused by the inactivation of the VHL gene and it is characterized by diverse types of high vasculated tumors of benign and malign nature. This paper reports the clinical characteristics and prenatal diagnosis of a woman with von Hippel-Lindau syndrome, who constitutes the first exclusion prenatal case by DNA analysis of the Von Hippel-Lindau syndrome in Latin-American population.