RESUMEN
Schwannomatosis is a tumor suppressor syndrome that causes multiple tumors along peripheral nerves. Formal diagnostic criteria were first published in 2005. Variability in clinical presentation and a relative lack of awareness of the syndrome have contributed to difficulty recognizing affected individuals and accurately describing the natural history of the disorder. Many critical questions such as the mutations underlying schwannomatosis, genotype-phenotype correlations, inheritance patterns, pathologic diagnosis of schwannomatosis-associated schwannomas, tumor burden in schwannomatosis, the incidence of malignancy, and the effectiveness of current, or new treatments remain unanswered. A well-curated registry of schwannomatosis patients is needed to facilitate research in field. An international consortium of clinicians and scientists across multiple disciplines with expertise in schwannomatosis was established and charged with the task of designing and populating a schwannomatosis patient registry. The International Schwannomatosis Registry (ISR) was built around key data points that allow confirmation of the diagnosis and identification of potential research subjects to advance research to further the knowledge base for schwannomatosis. A registry with 389 participants enrolled to date has been established. Twenty-three additional subjects are pending review. A formal process has been established for scientific investigators to propose research projects, identify eligible subjects, and seek collaborators from ISR sites. Research collaborations have been created using the information collected by the registry and are currently being conducted. The ISR is a platform from which multiple research endeavors can be launched, facilitating connections between affected individuals interested in participating in research and researchers actively investigating a variety of aspects of schwannomatosis. © 2016 Wiley Periodicals, Inc.
Asunto(s)
Estudios de Asociación Genética , Neurilemoma/epidemiología , Neurilemoma/genética , Neurofibromatosis/epidemiología , Neurofibromatosis/genética , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Bases de Datos Factuales , Femenino , Pruebas Genéticas , Mutación de Línea Germinal , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neurilemoma/diagnóstico , Neurofibromatosis/diagnóstico , Fenotipo , Vigilancia de la Población , Sistema de Registros , Neoplasias Cutáneas/diagnóstico , Adulto JovenRESUMEN
OBJECTIVE: To longitudinally analyze changes in plexiform neurofibroma (PN) volume in relation to age and body growth in children and young adults with neurofibromatosis type 1 and inoperable, symptomatic, or progressive PNs, using a sensitive, automated method of volumetric MRI analysis. METHODS: We included patients 25 years of age and younger with PNs entered in a natural history study or in treatment trials who had volumetric MRI over > or =16 months. RESULTS: We studied 49 patients (median age 8.3 years) with 61 PNs and a median evaluation period of 34 months (range 18 to 70). The PN growth rates varied among patients, but were constant within patients. Thirty-four patients (69%) experienced > or =20% increase in PN volume during the observation period. PN volume increased more rapidly than body weight over time (p = 0.026). Younger patients had the most rapid PN growth rate. CONCLUSIONS: Volume increase of plexiform neurofibromas is a realistic and meaningful trial endpoint. In most patients plexiform neurofibroma growth rate exceeded body growth rate. The youngest patients had the fastest plexiform neurofibroma growth rate, and clinical drug development should be directed toward this population. Age stratification for clinical trials for plexiform neurofibromas should be considered.
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Envejecimiento/patología , Peso Corporal , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Neurofibroma Plexiforme/patología , Neurofibromatosis 1/patología , Niño , Femenino , Humanos , Masculino , Invasividad Neoplásica , Estadística como AsuntoRESUMEN
Perfusion parameters (PP) and early transplant outcome data from 332 consecutive ECD type kidneys machine preserved on the Waters RM-3 apparatus were reviewed and analyzed to examine the validity of using suboptimal PPs (renal resistance of .41-.60) as a criterion for discarding kidneys. Overall discard rate was 23.5%, with 55% of these having "poor" PP as part of reason for discard. PP analysis after 4 hours on the RM-3 is presented. This encompasses 280 kidneys with renal resistance = .60. Sixty-six kidneys were discarded (23.5%). Of the 214 transplanted kidneys, 146 had immediate function (IF; 68%), 63 had delayed function (DGF; 29%), and 5 never functioned (PNF; 2%). Of the 30 transplanted kidneys with renal resistance .40 to .60, 16 (53%) had IF versus 58% in kidneys with renal resistance = .40 (P = .125). Two of the five PNF kidney had renal resistance > .40. The PP-related discard rate in the renal resistance .41 to .60 kidneys was 51% versus 17% in the renal resistance = .40 (P = .01). Based on our observations kidneys with renal resistance = .60 should not be discarded strictly based on "suboptimal perfusion parameters." This presents an opportunity for a decrease in discard rates of ECD kidneys.
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Trasplante de Riñón/métodos , Trasplante de Riñón/fisiología , Riñón , Preservación de Órganos/métodos , Humanos , Persona de Mediana Edad , Selección de Paciente , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Spondylothoracic dysplasia (STD, MIM#277300) is an autosomal recessive disorder with high prevalence in the Puerto Rican population. It is generally regarded as a lethal condition. Since Jarcho and Levin described it in 1938, it has been referred to as spondylocostal dysplasia, costovertebral dysplasia, Jarcho-Levin syndrome and STD. We have prospectively characterized 27 patients with STD by detailed physical examination, pedigree analysis, thoracic CT scans, and pulmonary function tests (PFTs). Diagnoses were established using spinal radiographs and 3-D reconstructive CT scans to demonstrate fusion of the ribs at the costo-vertebral junction with a fan-like (crab-like) configuration of the thorax. Vertebral segmentation and formation defects were seen throughout the spine with a decrease in the number of vertebral bodies. Characteristic vertebral shape consisted of a decrease in antero-posterior diameter and an increase in lateral length, giving the vertebra a sickle shape. Eight out of 18 prospectively follow patients died within the first 6 months of life, a 44% mortality rate. Cause of death was respiratory insufficiency secondary to pneumonia and pulmonary restriction. This is an important finding since the vast majority of STD syndrome patients cited in the medical literature have died in the newborn and early childhood periods. Age of the remaining patients ranged from 4 months to 47 years. This represents the largest collection of patients with STD reported and it has allowed us to determine a detailed phenotype. Given 56% survival at 6 months, we show that STD is not a lethal syndrome.
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Anomalías Múltiples/patología , Anomalías Musculoesqueléticas/patología , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/mortalidad , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Anomalías Musculoesqueléticas/diagnóstico , Anomalías Musculoesqueléticas/genética , Anomalías Musculoesqueléticas/mortalidad , Linaje , Fenotipo , Estudios Prospectivos , Puerto Rico , Radiografía Torácica , Costillas/anomalías , Costillas/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología , Síndrome , Tórax/anomalías , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Plexiform neurofibroma (PNF) is a typical feature of neurofibromatosis 1 (NF1). About 10% of patients with NF1 develop malignant peripheral nerve-sheath tumours (MPNST), usually arising from PNF, and this is the major cause of poor survival. A better prognosis can be achieved if the tumours are diagnosed at an early stage. Our objective was to establish MRI criteria for MPNST and to test their usefulness in detecting early malignant change in PNF. MRI was performed on 50 patients with NF1 and nerve-sheath tumours, of whom seven had atypical pain, tumour growth or neurological deficits indicative of malignancy; the other 43 were asymptomatic. On MRI all seven symptomatic patients had inhomogeneous lesions, due to necrosis and haemorrhage and patchy contrast enhancement. In one patient, the multiplicity of confluent tumours with inhomogeneous areas in addition to central lesions did not allow exclusion of malignancy. Only three of the 43 asymptomatic patients had comparable changes; the other 40 patients had tumours being of relatively homogeneous structure on T1- and T2-weighted images before and after contrast enhancement. All three asymptomatic patients with inhomogeneous lesions were shown to have MPNST.
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Neoplasias de la Vaina del Nervio/etiología , Neoplasias de la Vaina del Nervio/patología , Neurofibromatosis 1/complicaciones , Adolescente , Adulto , Diagnóstico Diferencial , Femenino , Hemorragia , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Necrosis , Dolor/etiología , Sensibilidad y EspecificidadRESUMEN
This article describes some types of growth in plexiform neurofibroma (PNF) on magnetic resonance images (MRI). This tumor is almost exclusively associated with NF1. On MRI, the tumor is depicted as a hyperintensive area on T2-weighted images. We distinguished 3 patterns of tumor growth: first, the superficial and non-invasive tumors, that are restricted to the cutis and subcutis, only eventually having outgrowth to the muscles beneath and are slow growing. Second, the displacing PNF that develop in deeper layers of the skin or within the body. They can grow to a large extent but do not invade adjacent muscles or skin. Thirdly, the invasive type with no visible margins that cannot be resected without adjacent structures or organs. A combination of these tumors can sometimes be noted, e.g. a displacing tumorous nerve developing in a large lumpy, non-invasive PNF. These categories might be used as a current guideline for medical advice, surgical treatment planning and medication trials.
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Neurofibroma Plexiforme/patología , Neurofibromatosis 1/patología , División Celular , Humanos , Imagen por Resonancia Magnética , Neurofibroma Plexiforme/clasificación , Estudios RetrospectivosRESUMEN
Neurofibromatosis type 1 (NF1) is one of the most common neurogenetic diseases affecting adults and children. Neurofibromas are one of the most common of the protean manifestations of NF1. Plexiform neurofibromas, which will frequently cause cosmetic abnormalities, pain, and neurologic deficits, are composed of "neoplastic" Schwann cells accompanied by other participating cellular and noncellular components. There is increasing evidence that loss of NF1 expression in neoplastic Schwann cells is associated with elevated levels of activated RAS, supporting the notion that the NF1 gene product, neurofibromin, acts as a growth regulator by inhibiting ras growth-promoting activity. In addition, there is increasing evidence that other cooperating events, which may be under cytokine modulation, are important for neurofibroma development and growth. Treatment of plexiform neurofibromas has been empiric, with surgery being the primary option for those with progressive lesions causing a major degree of morbidity. The efficacy of alternative treatment approaches, including the use of antihistamines, maturation agents, and antiangiogenic drugs, has been questionable. More recently, biologic-based therapeutic approaches, using drugs that target the molecular genetic underpinnings of plexiform neurofibromas or cytokines believed important in tumor growth, have been initiated. Evaluation of such trials is hindered by the unpredictable natural history of plexiform neurofibromas and difficulties in determining objective response in tumors that are notoriously large and irregular in shape. Innovative neuroimaging techniques and the incorporation of quality-of-life scales may be helpful in evaluation of therapeutic interventions. The ability to design more rational therapies for NF1-associated neurofibromas is heavily predicated on an improved understanding of the molecular and cellular biology of the cells involved in neurofibroma formation and growth.
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Terapia Biológica/métodos , Neurofibroma Plexiforme/tratamiento farmacológico , Neurofibromatosis 1/tratamiento farmacológico , Terapia Biológica/estadística & datos numéricos , Ensayos Clínicos como Asunto/métodos , Ensayos Clínicos como Asunto/estadística & datos numéricos , Humanos , Neurofibroma Plexiforme/patología , Neurofibroma Plexiforme/cirugía , Neurofibromatosis 1/patología , Neurofibromatosis 1/cirugíaRESUMEN
OBJECTIVE: To determine the spectrum of connexin 26 (Cx26) mutations and their phenotypes in children with sensorineural hearing loss (SNHL) or mixed hearing loss (MHL). DESIGN: Children with SNHL or MHL were prospectively tested for mutations in the entire coding region of the Cx26 gene. PATIENTS: Children with SNHL or MHL with no obvious etiology for the hearing loss. RESULTS: Between December 1, 1998, and July 1, 2000, 107 patients with SNHL or MHL from 99 families underwent Cx26 testing. Most patients were aged 1 week to 16 years (61 boys and 46 girls). Thirty (30%) of 99 probands had Cx26 mutations: biallelic mutations were detected in 18 (9 homozygous and 9 compound heterozygous) and single mutations were detected in 12. Twelve previously reported mutations (35delG, 167delT, E47X, L90P, M34T, G12V, V37I, R143W, V84L, V153I, V27I, and 310del14) and 3 novel mutations (E129K, T8M, and N206S) were found. Hearing loss in patients with biallelic Cx26 mutations ranged from unilateral high frequency to bilateral profound. Four children, 2 with biallelic mutations, had temporal bone abnormalities. CONCLUSIONS: Connexin 26 mutations are common in children with SNHL, and it is likely that the homozygous and compound heterozygous mutations cause the SNHL. However, pathogenicity is less certain when only a single Cx26 mutation is present. Patients with biallelic Cx26 mutations had a slightly higher incidence of milder hearing loss than in previous studies. Children with SNHL or MHL should be tested for Cx26 mutations early in their evaluation.
Asunto(s)
Conexinas/genética , Pérdida Auditiva Sensorineural/genética , Adolescente , Niño , Preescolar , Conexina 26 , Sordera/complicaciones , Sordera/genética , Femenino , Pérdida Auditiva Sensorineural/complicaciones , Humanos , Lactante , Recién Nacido , Masculino , Mutación , FenotipoRESUMEN
BACKGROUND: Symptomatic involvement of the gastrointestinal tract in children with neurofibromatosis type 1 (NF1) is rare. Most reported complications in adults are caused by the presence of neurofibromas in the stomach, small bowel, or mesentery. In contrast, abdominal pain in children with NF1 may be the result of nonanatomic causes, such as migraine. There are no previous reports of an association between abdominal migraine and NF1. METHODS: Children with abdominal migraine were identified from a group of children with NF1, all of whom had been followed up for a minimum of 3 years. Medical records of cases were reviewed independently by two authors. MEDLINE was searched via PubMed for all reports of children with NF1 and any associated gastrointestinal involvement. RESULTS: Six children with NF1 and intermittent, episodic, severe abdominal pain are reported. Investigations for obstructive or inflammatory causes of abdominal pain were negative. All patients had previously been diagnosed with migraine headaches by a neurologist. In five of the six patients, propranolol (10-15 mg three times daily) resulted in relief of their abdominal pain within days of starting therapy. Our review identified 24 children in the medical literature with gastrointestinal complications of NF1, mostly secondary to visceral neurofibromas. In almost all of these cases, clinical examination and simple radiologic investigations led to the definitive diagnosis. There were no reports of abdominal migraine complicating NF1. CONCLUSIONS: Abdominal pain secondary to migraine is an unrecognized cause of abdominal pain in children with NF1 and may be more common than anatomic causes of abdominal pain in children with NF1. In children with NF1 and severe recurrent abdominal pain in whom an evaluation for anatomic lesions is negative, a trial of migraine therapy may be indicated.
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Dolor Abdominal/etiología , Trastornos Migrañosos/complicaciones , Neurofibromatosis 1/complicaciones , Propranolol/uso terapéutico , Dolor Abdominal/tratamiento farmacológico , Antagonistas Adrenérgicos beta/uso terapéutico , Niño , Preescolar , Femenino , Humanos , MEDLINE , Masculino , Neurofibroma , SíndromeRESUMEN
PURPOSE: It can be difficult to differentiate clinically between hemifacial microsomia (HFM) and Townes-Brocks syndrome (TBS). The distinction is important because TBS is inherited as an autosomal dominant trait, whereas HFM is sporadic. METHODS: We performed a retrospective analysis of eight patients with HFM-expanded spectrum and anal anomalies to determine whether this subset has TBS. RESULTS: Two patients had major phenotypic findings of TBS. Sequencing of SALL1, the gene mutated in TBS, in four of the eight patients revealed one with a C --> T transition (resulting in a nonsense mutation R276X) at a previously identified mutational "hot spot." CONCLUSION: Patients with overlapping features of both syndromes should be screened for SALL1 mutations.
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Anomalías Múltiples/genética , Asimetría Facial/genética , Mutación/genética , Factores de Transcripción/genética , Anomalías Múltiples/fisiopatología , Ano Imperforado/genética , Secuencia de Bases , Análisis Mutacional de ADN , Oído Externo/anomalías , Asimetría Facial/fisiopatología , Femenino , Deformidades Congénitas de la Mano/genética , Pérdida Auditiva Sensorineural/genética , Humanos , Masculino , Mandíbula/anomalías , Síndrome , Pulgar/anomalíasRESUMEN
Progress in understanding the biology of the neurofibromatoses (NF1 and NF2) offers hope for the development of new, effective methods of treatment. In May 2000, the National Institute of Neurological Disorders and Stroke (NINDS) hosted a workshop that included leading researchers and clinicians from the NF community. The goal of the meeting was to assess current knowledge and identify priorities for future research. Needs identified included the development of better animal models, further study of the function of the NF1 and NF2 genes, and investigation of the role of modifier genes. The participants agreed that it will also be important to define further the natural history of NF1 and NF2 and to develop an infrastructure to support clinical trials. They also discussed the possible creation of research consortia and NF centers to promote the integration of basic and clinical research.
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Neurofibromatosis/diagnóstico , Neurofibromatosis/genética , Neurofibromatosis/terapia , Animales , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Terapia Genética , Humanos , Resultado del TratamientoAsunto(s)
Factor V/genética , Pruebas Genéticas , Mutación , Anticoagulantes/metabolismo , Genotipo , Heterocigoto , Homocigoto , Humanos , Factores de RiesgoRESUMEN
Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder whose major feature is the occurrence of multiple neurofibromas, which are benign tumors of the nerve sheath. It affects an estimated one in 3000 to 4000 individuals. In addition to neurofibromas, there are many other clinical manifestations, including malignant tumors such as gliomas or malignant peripheral nerve sheath tumors, and nontumor effects such as skeletal dysplasia and learning disability. Diagnosis is established on the basis of clinical criteria. Molecular genetic testing is feasible, but the large size of the gene and wide range of pathogenic mutations have so far impeded the development of a clinical diagnostic test. Insights into pathogenesis have followed from identification of the NF1 gene and the development of animal models. The major function of the gene product appears to be regulation of the ras protein. Tumors are believed to arise by the loss of function of the NF1 protein, suggesting that NF1 behaves as a tumor suppressor gene. Heterozygous effects on some cell types are also likely, however. The role of ras in the pathogenesis of tumors in NF1 has suggested an approach to treatment using ras inhibitors, some of which are likely to begin in clinical trials in NF1 patients in the near future.
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Neurofibromatosis 1/terapia , Animales , Neoplasias Encefálicas/etiología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Manchas Café con Leche/etiología , Transformación Celular Neoplásica/genética , Femenino , Genes Dominantes , Genes de Neurofibromatosis 1 , Glioma/etiología , Glioma/patología , Glioma/terapia , Guanosina Trifosfato/metabolismo , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/etiología , Discapacidades para el Aprendizaje/etiología , Discapacidades para el Aprendizaje/terapia , Leucemia/etiología , Leucemia/terapia , Masculino , Ratones , Ratones Noqueados , Neurofibroma/etiología , Neurofibroma/patología , Neurofibroma/terapia , Neurofibromatosis 1/diagnóstico , Neurofibromatosis 1/patología , Neurofibromina 1/química , Neurofibromina 1/fisiología , Estructura Terciaria de Proteína , Rabdomiosarcoma/etiología , Rabdomiosarcoma/patología , Rabdomiosarcoma/terapia , Escoliosis/etiología , Escoliosis/patología , Proteínas ras/metabolismoRESUMEN
This unit provides an introduction to clinical cytogenetics. It opens with indications for prenatal and postnatal chromosome analysis, followed by a brief discussion of the applications of fluorescence in situ hybridization (FISH). It suggests tissue sources for prenatal and postnatal analysis, and closes with a review of numerical and structural chromosome abnormalities. This unit provides an introduction to clinical cytogenetics.
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Análisis Citogenético , Aberraciones Cromosómicas , Femenino , Genética Médica , Humanos , Hibridación Fluorescente in Situ , Embarazo , Diagnóstico PrenatalAsunto(s)
Genética Médica , Ética Médica , Asesoramiento Genético , Humanos , Jurisprudencia , PenetranciaRESUMEN
Neurofibromatosis type 1 (NF1) represents a major risk factor for development of malignancy, particularly malignant peripheral nerve sheath tumors (MPNST), optic gliomas, other gliomas, and leukemias. The oncologist will see NF1 patients referred for treatment of malignancy, and should be alert to the possibility of undiagnosed NF1 among patients with cancer. Brain tumors tend to have a more indolent course in NF1 than in the general population, and hence are best managed conservatively. MPNST, in contrast, do not respond to standard chemotherapy or radiation therapy. The most effective treatment of MPNST appears to be early diagnosis and surgery, but early diagnosis is hampered by frequent occurrence within preexisting large tumors, making new growth or change difficult to detect. New insights into pathogenesis now offer hope of development of specific methods of treatment with reduced toxicity and more precise molecular targeting. There is an urgent need, however, to develop methods to measure tumor growth and monitor outcomes, develop preclinical drug screening systems, and further explore the pathogenesis of the disorder to determine whether mechanisms other than Ras regulation may be important in pathogenesis.
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Neurofibromatosis 1/complicaciones , Glioma/etiología , Humanos , Leucemia/etiología , Neurilemoma/etiología , Neurofibromatosis 1/terapia , FenotipoRESUMEN
Although it is well recognized that a peripheral vasculopathy may occur in patients with neurofibromatosis 1 (NF1), it is unclear whether cardiovascular abnormalities are more common. We reviewed the frequency of cardiovascular abnormalities, in particular, cardiovascular malformations (CVMs), among 2322 patients with definite NF1 in the National Neurofibromatosis Foundation International Database from 1991-98. Cardiovascular malformations were reported in 54/2322 (2.3%) of the NF1 patients, only 4 of whom had Watson syndrome or NF1-Noonan syndrome. There was a predominance of Class II "flow" defects [Clark, 1995: Moss and Adams' Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. p 60-70] (43/54, 80%) among the NF1 patients with CVMs. Pulmonic stenosis, that was present in 25 NF1 patients, and aortic coarctation, that occurred in 5, constitute much larger proportions of all CVMs than expected. Of interest was the paucity of Class I conotruncal defects (2 patients with tetralogy of Fallot), and the absence of atrioventricular canal, anomalous pulmonary venous return, complex single ventricle and laterality defects. Besides the 54 patients with CVMs, there were 27 patients with other cardiac abnormalities (16 with murmur, 5 with mitral valve prolapse, 1 with intracardiac tumor, and 5 with electrocardiogram abnormalities). No patient in this study had hypertrophic cardiomyopathy. There were 16 patients who had a peripheral vascular abnormality without an intracardiac CVM, plus an additional 4 patients among those with a CVM who also had a peripheral vascular abnormality.
Asunto(s)
Anomalías Cardiovasculares/etiología , Anomalías Cardiovasculares/genética , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico , Coartación Aórtica/complicaciones , Coartación Aórtica/diagnóstico , Niño , Preescolar , Electrocardiografía , Femenino , Soplos Cardíacos/complicaciones , Soplos Cardíacos/diagnóstico , Humanos , Masculino , Prolapso de la Válvula Mitral/complicaciones , Prolapso de la Válvula Mitral/diagnóstico , Síndrome de Noonan/complicaciones , Síndrome de Noonan/diagnóstico , Estenosis de la Válvula Pulmonar/complicaciones , Estenosis de la Válvula Pulmonar/diagnóstico , SíndromeAsunto(s)
Enfermedades Fetales/genética , Aumento de la Imagen , Imagen por Resonancia Magnética , Diagnóstico Prenatal , Esclerosis Tuberosa/genética , Epéndimo/anomalías , Epéndimo/patología , Femenino , Enfermedades Fetales/diagnóstico , Asesoramiento Genético , Edad Gestacional , Humanos , Recién Nacido , Embarazo , Esclerosis Tuberosa/diagnóstico , Ultrasonografía PrenatalRESUMEN
The sequence of the human genome is very nearly in hand; the first draft has been completed, and the finished sequence will be available years ahead of schedule. Already, advances in medical genetics have affected the day-to-day practice of medicine by providing more powerful approaches to diagnosis of genetic disorders and cancer. But the full impact of the integration of genetics into medical practice lies before us.