van Irene Langen

EXTENSION OF THE CLINICAL SPECTRUM OF DANON DISEASE

Danon disease is caused by mutations in the lysosome-associated membrane protein 2 (LAMP2).1 It is an X-linked dominant disorder characterized by severe cardiomyopathy, mental retardation, and mild myopathy in men, and cardiomyopathy in female carriers.2 All mutations reported so far have resulted in absence of LAMP2 staining in affected men.1–4nn### Case reports.nnThe proband, III-4 (figure e-1 on the Neurology ® Web site at www.neurology.org), with normal intelligence, was referred at age 46. Since childhood, he had slowly progressive weakness of legs and later arms, with subsequent dysarthria and swallowing difficulties. He is now 63 and is almost completely wheelchair bound. His vision has gradually diminished to finger counting. Examination showed a myopathic face, gynecomastia, moderate weakness of limb girdle muscles, and minor distal weakness. Perimetry demonstrated central scotomas, while fluorescein angiography showed a Bullseye maculopathy, but electroretinography was normal. At the age of 61 a pacemaker was implanted because of a sick sinus syndrome. Echocardiography revealed left ventricular hypertrophy with preserved systolic function.nnSubject III-3 presented at the age of 63 years with muscle weakness since age 45. His intellect and vision were normal. In retrospect, he had been a little weaker than his peers since his teens. He showed predominant …

A new mutation in the prion protein gene: A patient with dementia and white matter changes

Article abstract The authors describe the clinical characteristics, MRI abnormalities, and molecular findings in a patient with a novel variant of a two-octarepeat insertion mutation in the prion protein gene. This patient presented with moderately progressive dementia of presenile onset and gait ataxia. MRI showed extensive cortical atrophy and white matter abnormalities. The mutation consists of a two-octarepeat insertion mutation and irregularities in the nucleotide sequence of the octarepeat region.

Rationale and design of the CAREFUL study : The yield of CARdiogenetic scrEening in First degree relatives of sudden cardiac and UnexpLained death victims <45 years

Background. Sudden cardiac death (SCD) in the young (1-45 years) is a strong risk factor for the presence of inherited cardiac diseases in surviving first-degree relatives. Postmortem investigation of the victim and cardiogenetic evaluation of the first-degree relatives is indicated to detect inherited cardiac diseases and treat relatives at an early stage to prevent SCD. In the Netherlands, postmortem investigation is often not performed and relatives of SCD and sudden unexplained death (SUD) victims are rarely evaluated for inherited cardiac diseases. Methods. A prospective population-based follow-up study carried out in two intervention regions and two control regions. In the intervention regions a comprehensive intervention (stimulate autopsy and storage of victims DNA and the referral of first-degree relatives for cardiogenetic evaluation) is applied in a ‘top down’ and ‘bottom up’ mode. In each region, young sudden death victims are registered and for all cases performance of autopsy and evaluation of relatives in a cardiogenetics outpatient clinic will be determined. Expected results. The study will provide information on the incidence of sudden death in the young and the proportion of diagnosed inherited cardiac diseases. Moreover, the additional value of the introduction of two different preventive strategies directed at early detection of inherited cardiac diseases in first-degree relatives to usual care will be evaluated. Conclusion. The CAREFUL study will help to set a new standard of care in the evaluation of young sudden death victims and their relatives to identify the presence of inherited cardiac diseases, in order to prevent sudden death. (Neth Heart J 2010;18:286-90.)

Haplotype sharing test maps genes for familial cardiomyopathies

van der Zwaag PA, van Tintelen JP, Gerbens F, Jongbloed JDH, Boven LG, van der Smagt JJ, van der Roest WP, van Langen IM, Bikker H, Hauer RNW, van den Berg MP, Hofstra RMW, te Meerman GJ. Haplotype sharing test maps genes for familial cardiomyopathies.