RESUMEN
Myotonic dystrophy type 1 is an autosomal dominant, inherited multiorgan disorder that can affect people of all ages. It is the most prevalent inherited muscular disease in adults. Late diagnosis points to limited knowledge among the medical community that symptoms other than typical muscular symptoms can dominate. The condition often worsens with each generation and some families are severely affected. Significantly delayed diagnosis means a risk of more serious development of the disorder and inadequate symptomatic treatment. We hope that this clinical review article may lead to more rapid diagnosis and better follow-up of this patient group.
Asunto(s)
Distrofia Miotónica , Distrofia Miotónica/diagnóstico , Distrofia Miotónica/complicaciones , Humanos , Diagnóstico Tardío , AdultoRESUMEN
Neurofibromatosis type 1 (NF1) is a genetic, autosomal dominant multi-organ disease characterized by susceptibility to tumor formation, changes in skin pigmentation, skeletal abnormalities, and neuropsychological deficits. Clinical studies have shown impaired health-related quality of life (HQoL) in adults with NF1. However, little is known about HQoL in non-clinical NF1 samples. We conducted a cross-sectional self-report survey of 142 persons with NF1 (M age = 50.3 years, SD = 12.0, range 32 to 80; 62.0% females) recruited from non-clinical settings. Several HQoL domains, including life satisfaction, mental health, sleep, pain, gastrointestinal problems, oral health, and social support, were compared between the NF1 sample and 46,293 controls from the HUNT3 population study. We also examined gender differences within the NF1 sample and predictors of HQoL. Compared to controls, the NF1 sample reported significantly poorer life satisfaction, mental health, sleep, and oral health, and more pain, gastrointestinal problems, comorbid diseases, and memory problems. Several HQoL domains were significantly correlated. Mental health was the only unique significant predictor of overall life satisfaction. Women with NF1 reported significantly more mental health, sleep, and pain problems than men with NF1. Mental health assessment and management should be integrated into clinical care of persons with NF1 to potentially improve their HQoL.
Asunto(s)
Encuestas Epidemiológicas , Neurofibromatosis 1/fisiopatología , Neurofibromatosis 1/psicología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios Transversales , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Calidad de Vida/psicología , Autoinforme , Conducta Social , Apoyo Social , Encuestas y CuestionariosRESUMEN
Clinical genetic testing (CGT) of children with autism spectrum disorder (ASD) may have positive and negative effects. Knowledge about parents' attitudes is needed to ensure good involvement of caregivers, which is crucial for accurate diagnosis and effective clinical management. This study aimed to assess parents' attitudes toward CGT for ASD. Parent members of the Norwegian Autism Society were given a previously untested questionnaire and 1455 answered. Linear regression analyses were conducted to evaluate contribution of parent and child characteristics to attitude statements. Provided it could contribute to a casual explanation of their child's ASD, 76% would undergo CGT. If it would improve the possibilities for early interventions, 74% were positive to CGT. Between 49-67% agreed that CGT could have a negative impact on health insurance, increase their concern for the child's future and cause family conflicts. Parents against CGT (9%) were less optimistic regarding positive effects, but not more concerned with negative impacts. The severity of the children's ASD diagnosis had a weak positive association with parent's positive attitudes to CGT (p-values range from <0.001 to 0.975). Parents prefer that CGT is offered to those having a child with ASD (65%), when the child's development deviates from normal (48%), or before pregnancy (36%). A majority of the parents of children with ASD are positive to CGT due to possibilities for an etiological explanation.
Asunto(s)
Actitud , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/genética , Pruebas Genéticas , Padres/psicología , Trastorno Autístico/diagnóstico , Trastorno Autístico/genética , Femenino , Humanos , Modelos Lineales , Masculino , Noruega , Encuestas y CuestionariosRESUMEN
Was district medical officer Jensen the first doctor to describe patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN) in Volda in 1830? A case series of four siblings with the same disease written by district medical officer Peter Jensen (1799-1832) in Aalesund in 1830, was published in the Norwegian medical journal Eyr in 1832. The children, who were healthy almost up to school age, developed dystonic involuntary movements and deformities in all extremities, lost their ability to speak and were emaciated before they died at around the age of nine years. Further information about the family and a fifth affected child has been found in the parish records. The clinical picture is consistent with Pantothenate Kinase-Associated Neurodegeneration (PKAN), a rare condition with basal ganglia iron deposition, described in 1922 by the German neuropathologists Julius Hallervorden (1882-1965) and Hugo Spatz (1888-1969). The disease was formerly called Hallervorden-Spatz syndrome, but because of the medical activities undertaken by these two researchers before and during the Second World War, this eponym is no longer recommended.
Asunto(s)
Neurodegeneración Asociada a Pantotenato Quinasa , Niño , Femenino , Historia del Siglo XIX , Humanos , Imagen por Resonancia Magnética , Masculino , Noruega , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico , Neurodegeneración Asociada a Pantotenato Quinasa/historia , Enfermedades Raras/historia , HermanosRESUMEN
Myotonic dystrophy (DM) is a progressive multi-systemic disorder characterized by myotonia and muscle weakness where currently no effective treatment or cure to prevent or delay the disorder exists. This study used mixed methods to examine the experience of living with DM, in patients and their close relatives. Thirteen patients and eight next of kin responded completing Quality of Life and Psychological distress questionnaires in this cross-sectional study, and participating in a semi-structured interview. The findings indicate a higher level of anxiety and hopelessness in next of kin compared to patients, while patients were more depressed. Next of kin reported higher physical, but lower emotional quality of life than patients. Qualitative interviews confirmed the questionnaire findings. The findings from this study may be helpful in genetic counseling. Genetic counselors and geneticists should not only be aware of the burden of being a next of kin, but include discussions about opportunities to minimize the burden in families affected with DM. The findings may be of relevance in counseling for other types of neuromuscular disorders.
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Actividades Cotidianas/psicología , Distrofia Miotónica/psicología , Calidad de Vida/psicología , Estrés Psicológico/psicología , Adaptación Psicológica , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distrofia Miotónica/complicaciones , Estrés Psicológico/etiología , Encuestas y CuestionariosAsunto(s)
Neurofibromatosis 2/diagnóstico , Neurofibromatosis 2/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Niño , Femenino , Eliminación de Gen , Genes de la Neurofibromatosis 2 , Estudios de Asociación Genética , Mutación de Línea Germinal , Humanos , Mutación , Fenotipo , Piel/patologíaRESUMEN
Schwannomatosis is a recently delineated inherited condition that has clinical overlap with neurofibromatosis type 2 (NF2). Diagnostic criteria have been developed to distinguish schwannomatosis from NF2, but the existence of mosaic NF2, which may closely mimic schwannomatosis, makes even these criteria problematic. In particular, it is not clear why there is a relative sparing of the cranial nerves from schwannomas in schwannomatosis. We have identified two individuals with schwannomatosis and a unilateral vestibular schwannoma (VS), where a diagnosis of NF2 has been excluded. A third case with an identified SMARCB1 mutation was reported by two radiologists to have a VS, but this was later confirmed as a jugular schwannoma. These cases question whether the current exclusion of a VS from the clinical diagnosis of schwannomatosis is justified.
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Neurilemoma/diagnóstico , Neurilemoma/genética , Neurofibromatosis/diagnóstico , Neurofibromatosis/genética , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/genética , Adulto , Anciano , Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Neurofibromatosis 2/diagnóstico , Neurofibromatosis 2/genética , Proteína SMARCB1 , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Neurofibromatosis type 2 (NF2) is a rare and severe autosomal dominant disorder caused by mutations in a tumour suppressor gene. This article reviews NF2 and its treatment with auditory brainstem implantation. MATERIAL AND METHODS: The review is based on the authors' experience with the disease and literature identified through a non-systematic search of PubMed. RESULTS: NF2 is caused by loss-of-normal function of the tumour suppressor protein merlin. Merlin normally suppresses cell growth and proliferation. The clinical picture is dominated by neurological symptoms, caused by multiple tumours - mainly schwannomas and meningeomas. The hallmark of the disease is development of bilateral vestibular schwannomas, and the most common presenting symptom in adults is progressive hearing loss. Presenile cataract, ocular motility disorders, peripheral neuropathy and skin tumours are other common findings. The majority of patients become deaf, many patients become severely disabled and life expectancy is reduced. The goal of management is conservation of function and maintenance of quality of life. Auditory brainstem implants stimulate the cochlear nucleus directly and provide substantial auditory benefits to patients with NF2. INTERPRETATION: A multidisciplinary approach in specialty centres is recommended. Management by an experienced team reduces mortality and improves outcome after surgery. Auditory brainstem implantation is an important part of the hearing rehabilitation in these patients. Emerging knowledge of the molecular disease mechanisms offers hope for new therapeutic strategies.
Asunto(s)
Implantación Auditiva en el Tronco Encefálico/métodos , Neurofibromatosis 2/cirugía , Adulto , Niño , Sordera/rehabilitación , Sordera/cirugía , Humanos , Imagen por Resonancia Magnética , Neurilemoma/patología , Neurilemoma/cirugía , Neurofibromatosis 2/patología , Neurofibromatosis 2/rehabilitación , Calidad de Vida , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVES: The primary aim was to evaluate which investigation performed after sonographic detection of central nervous system (CNS) or skeletal anomalies that had highest diagnostic yield. The secondary aim was to estimate recurrence risk. Design. Retrospective review of patients' records. SETTING: Tertiary fetal medicine referral center. SAMPLE: Pregnancy terminations (n=97) because of CNS or skeletal anomalies during a 17-year period, within 12-24 weeks gestation. METHODS: Two medical geneticists and one genetic counselor reviewed charts independently. MAIN OUTCOME MEASURES: Primary ultrasound diagnosis, change in diagnosis following supplementary examinations in addition to prenatal ultrasound (medical history, autopsy, post-mortem X-ray, karyotyping, targeted DNA analysis and investigations for infection), the most useful method to determine diagnosis, and recurrence risk estimate including inter-rater agreement. RESULTS: Mean gestational age was 19.8 weeks. All three investigators agreed in each case on which investigation constituted the best basis to determine the most precise diagnosis. The examinations performed in addition to prenatal ultrasound provided important diagnostic information in 54 cases (56%) and altered recurrence risk in 22 (23%) cases; in eight of these cases the risk estimate was increased. In nine cases (9%) the investigators disagreed in their estimates of recurrence risk. Kappa for inter-rater agreement was >0.90. CONCLUSIONS: A panel of diagnostic investigations, depending on the organ system involved, allows for a more precise diagnosis and a more reliable estimate of recurrence risk than prenatal ultrasound alone. In some instances, recurrence risk estimation is not straightforward as evidenced by lack of consensus.
Asunto(s)
Anomalías Múltiples/diagnóstico por imagen , Sistema Nervioso Central/anomalías , Asesoramiento Genético , Anomalías Musculoesqueléticas/diagnóstico por imagen , Anomalías Múltiples/diagnóstico , Aborto Inducido , Adulto , Amniocentesis , Autopsia , Sistema Nervioso Central/diagnóstico por imagen , Muestra de la Vellosidad Coriónica , Femenino , Humanos , Cariotipificación , Anomalías Musculoesqueléticas/diagnóstico , Embarazo , Radiografía , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Ultrasonografía PrenatalRESUMEN
AIM: The aim of this study was to estimate the incidence and prevalence of mucopolysaccharidoses (MPS disorders) in Scandinavia. METHODS: The retrospective period used for the incidence study covered the period from 1975 to 2004 in Sweden and Denmark and from 1979 to 2004 in Norway. Prevalence was derived from the number of MPS patients alive as of December 31, 2007. RESULTS: The incidence of all MPS disorders was 1.75 cases in Sweden, 3.08 cases in Norway and 1.77 cases in Denmark per 100 000 newborns. The incidence of MPS I was the most common in all three countries, with 0.67, 1.85 and 0.54 cases per 100 000 newborns, respectively; for MPS II, numbers were 0.27, 0.13 and 0.27, respectively. For patients with other MPS disorders the incidence varied widely. The prevalence for all MPS disorders was 4.24, 7.06 and 6.03 per 1 000 000 inhabitants in Sweden, Norway and Denmark, respectively. CONCLUSION: From three Scandinavian countries the incidence of MPS disorders is retrospectively evaluated for 25 years in Norway and 30 years in Sweden and Denmark. Incidence and prevalence studies of lysosomal disorders are prerequisites for cost benefit calculations in the face of newly developed and expensive therapies in the future.
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Mucopolisacaridosis/epidemiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Prevalencia , Países Escandinavos y Nórdicos/epidemiología , Adulto JovenRESUMEN
Huntington's disease is an autosomal dominant slowly degenerative apoptotic condition in CNS, in particular in striatum. It is characterized by involuntary movements; in particular chorea, personality changes and subcortical dementia. About 250 persons are diagnosed in Norway with the condition at any time, most are diagnosed between 35 and 55 years but onset before 20 years of age can be seen and diagnosis in later life is not rare. The average duration is about 15 years from diagnosis to death, but it can be considerably longer. Signs, symptoms and therapeutic challenges are mentioned in addition to molecular and clinical genetic aspects, in particular pre-symptomatic and prenatal diagnosis.
Asunto(s)
Enfermedad de Huntington , Adulto , Humanos , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/genética , Enfermedad de Huntington/terapia , Persona de Mediana Edad , Diagnóstico Prenatal , PronósticoRESUMEN
Background: Autism spectrum disorder and epilepsy often co-occur; however, the extent to which the association between autism symptoms and epilepsy is due to shared aetiology or to the direct effects of seizures is a topic of ongoing debate. Angelman syndrome (AS) is presented as a suitable disease model to explore this association. Methods: Data from medical records and questionnaires were used to examine the association between age of epilepsy onset, autism symptoms, genetic aberration and communication level. Forty-eight participants had genetically verified AS (median age 14.5 years; range 1-57 years). A measure of autism symptoms (the Social Communication Questionnaire; SCQ) was completed for 38 individuals aged ≥ 4 years. Genetic cause was subgrouped into deletion and other genetic aberrations of the 15q11-q13 area. The number of signs used to communicate (< 20 sign and ≥ 20 signs) was used as a measure of nonverbal communication. Results: Mean age of epilepsy onset was 3.0 years (range 3 months-7.8 years). Mean SCQ score for individuals without epilepsy was 13.6 (SD = 6.7) and with epilepsy 17.0 (SD = 5.6; p = 0.17); 58% used fewer than 20 signs to communicate. There were no age differences between groups according to presence of epilepsy, level of nonverbal communication or type of genetic aberration. SCQ scores were higher in individuals with the deletion than in those with other genetic aberrations (18.7 vs 10.8 p = 0.008) and higher in the group who used < 20 signs to communicate (19.4 vs 14.1 p = 0.007). Age of epilepsy onset was correlated with SCQ (r = - 0.61, p < 0.001). Multiple regression showed that age of seizure onset was significantly related to SCQ score (ß = - 0.90; p = 0.006), even when the type of genetic abnormality was controlled (R2 = 0.53; F = 10.7; p = 0.001). Conclusions: The study provides support for the notion that seizures themselves contribute more to autism symptoms than expected from the underlying genetic pathology alone. The study demonstrates how a rare genetic syndrome such as Angelman syndrome may be used to study the relation between epilepsy and autism symptomatology.
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Síndrome de Angelman/diagnóstico , Trastorno Autístico/diagnóstico , Epilepsia/diagnóstico , Adolescente , Adulto , Síndrome de Angelman/complicaciones , Trastorno Autístico/epidemiología , Niño , Preescolar , Epilepsia/epidemiología , Femenino , Humanos , Lactante , Masculino , Persona de Mediana EdadRESUMEN
Kinesin proteins are critical for various cellular functions such as intracellular transport and cell division, and many members of the family have been linked to monogenic disorders and cancer. We report eight individuals with intellectual disability and microcephaly from four unrelated families with parental consanguinity. In the affected individuals of each family, homozygosity for likely pathogenic variants in KIF14 were detected; two loss-of-function (p.Asn83Ilefs*3 and p.Ser1478fs), and two missense substitutions (p.Ser841Phe and p.Gly459Arg). KIF14 is a mitotic motor protein that is required for spindle localization of the mitotic citron rho-interacting kinase, CIT, also mutated in microcephaly. Our results demonstrate the involvement of KIF14 in development and reveal a wide phenotypic variability ranging from fetal lethality to moderate developmental delay and microcephaly.
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Discapacidad Intelectual/genética , Cinesinas/genética , Microcefalia/genética , Proteínas Oncogénicas/genética , Niño , Preescolar , Femenino , Humanos , Discapacidad Intelectual/patología , Cinesinas/química , Cinesinas/metabolismo , Mutación con Pérdida de Función , Microcefalia/patología , Mutación Missense , Proteínas Oncogénicas/química , Proteínas Oncogénicas/metabolismo , Linaje , Fenotipo , Dominios Proteicos , SíndromeRESUMEN
BACKGROUND: The link between chronic illness in children and their parents' sense of coherence has not previously been studied in Norway. MATERIAL AND METHOD: The study population was composed of two different samples. The first sample was randomised and taken from children in Norway aged 2 to 17 years in 1996. The other sample was not randomised and was taken from children aged 4 to 16 years staying at Frambu (national centre of expertise and information for rare disabilities) in the period from ultimo 1995 to primo 1997. Parents answered a questionnaire for both samples. RESULTS: The results showed a link between chronic illness and disabilities in children and their parents' poor sense of coherence. High odds for a poor sense of coherence were most common among parents of mentally disabled children (OR = 2.05, KI = 1.14-3.69). Parents of children with chronic illness and disabilities scored higher for the dimensions meaningfulness and comprehension, compared with parents who had children without such problems. CONCLUSIONS: Our findings indicate that parents of mentally disabled children are more vulnerable than parents of children without a chronic disease or functional impairment, and also more vulnerable than parents of children with other chronic disease/functional impairments.
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Adaptación Psicológica , Niños con Discapacidad/psicología , Padres/psicología , Calidad de Vida , Adolescente , Adulto , Niño , Preescolar , Enfermedad Crónica/psicología , Estudios Transversales , Femenino , Humanos , Lactante , Discapacidad Intelectual/psicología , Masculino , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Genetic research in autism spectrum disorder (ASD) is mainly performed in minors who are legally unable to provide consent. Thus, knowledge of the attitudes, fears, and expectations toward genetic research of the parents is important. Knowledge of the attitudes toward genetic research will improve cooperation between researchers and participants, and help establish confidence in ASD genetic research. The present study aimed to assess these attitudes. MATERIALS AND METHODS: Questionnaire-based assessments of attitudes toward genetic research and toward procedures in genetic research of n=1455 parents of individuals with ASD were performed. RESULTS: The main motivation for participation in genetic research is to gain more knowledge of the causes and disease mechanisms of ASD (83.6%), and to contribute toward development of improved treatment in the future (63.7%). The parents also had a positive attitude towards storing genetic information (54.3%) and they requested confidentiality of data (82.9%) and expressed a need to be informed about the purpose (89%) and progress of the research (83.7%). We found a slightly more positive attitude to participation in genetic research among older parents (P=0.015), among fathers compared with mothers (P=0.01), among parents of girls compared with boys (P=0.03), and infantile autism compared with Asperger syndrome (P=0.002). However, linear regression analysis showed that parent and child characteristics seem to have too small an influence on attitudes toward genetic research to be of any relevance (R(2)=0.002-0.02). CONCLUSION: Parents of children with ASD have, in general, a very positive attitude toward genetic research. Data confidentiality is important, and they express a need for information on the purpose and progress of the research.