Clinical and Mutational Characteristics of SMARD1 Patients in the Netherlands

OBJECTIVE: Describing clinical and mutational characteristics findings in Dutch SMARD1 patients. BACKGROUND: Since discovery of the IGHMBP2 gene causing spinal muscular atrophy with respiratory distress type 1 (SMARD1) in 2001, over 100 patients have been reported. SMARD1 is an uncommon variant of infantile SMA type 1 and is an autosomal recessive disorder with early respiratory difficulties, distal muscle weakness and contractures leading to foot deformities as the most striking clinical symptoms. In our study population six novel mutations of the IGHMBP2 gene were found, including a gene deletion of exon 2. DESIGN/METHODS: We present the Dutch cohort of SMARD1 patients containing 10 patients. RESULTS: Core features including early rapid and life threatening respiratory distress, generalized hypotonia, distal more than proximal muscle weakness and foot deformities were found in the majority of our population. In accordance with literature, some of the patients showed a milder phenotype. In all 10 patients mutations of both IGHMBP2 gene alleles were found. Six of them were novel mutations, including a gene deletion of exon 2. CONCLUSIONS: In this Dutch cohort of SMARD1 patients the key features of the disease are seen; early respiratory failure and distal muscle weakness due to a severe axonal neuropathy. A genotype fenotype correlation could not be established. Most patients died before the age of one year. Disclosure: Dr. Stalpers has nothing to disclose. Dr. Verrips has nothing to disclose. Dr. Poll-The has nothing to disclose. Dr. Cobben has nothing to disclose. Dr. Snoeck has nothing to disclose. Dr. De Coo has nothing to disclose. Dr. Brooks has nothing to disclose. Dr. Bulk has nothing to disclose. Dr. Gooskens has nothing to disclose. Dr. Fock has nothing to disclose. Dr. Verschuuren-Bemelmans has nothing to disclose. Dr. Sinke has nothing to disclose. Dr. de Visser has nothing to disclose. Dr. Lemmink has nothing to disclose.