title: Distally pronounced infantile spinal muscular atrophy with severe axonal and demyelinating neuropathy associated with the S230L mutation of SMN1.
abstract: Two Croatian siblings with atypical clinical findings in the presence of SMN1 gene mutations are reported. The girl presented with delayed motor development and weakness in hands and feet in her first year of life. She never stood or walked and developed scoliosis and joint contractures during childhood. Her hands and feet were non-functional when last seen at age 14 years. Her 4-year-old brother was more severely affected and had a clinical picture resembling infantile spinal muscular atrophy (SMA) type 1. He also showed unusual distally pronounced weakness and facial weakness. Both patients had no sensory deficits but gave evidence of a mixed axonal and demyelinating neuropathy with pronounced slowing in the distal nerve segments. Unexpectedly, both siblings showed a compound heterozygous SMN1 mutation (heterozygous deletion and missense mutation c.689C > T; p.S230L), thus confirming infantile SMA. In addition, next generation sequencing of 52 genes for hereditary neuropathies revealed a heterozygous missense mutation c.505T > C; p.Y169H in the SH3TC2 gene that was transmitted by the healthy father. Our observations widen the phenotypic consequences of SMN1 gene mutations and support the notion to look for additional genetic factors which may modify the clinical picture in atypical cases.
authors.affiliation: Institute of Human Genetics, Medical Faculty, Uniklinik RWTH Aachen, Aachen, Germany; Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria. Electronic address: sabine.rudnik@i-med.ac.at.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.affiliation: Department of Pediatrics, Zagreb Medical School, University Hospital Center, Zagreb, Croatia.
authors.forename: Nina
authors.initials: N
authors.lastname: Barisić
authors.affiliation: Institute of Human Genetics, Medical Faculty, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Eggermann
authors.affiliation: Institute of Human Genetics, Medical Faculty, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Nadina
authors.initials: N
authors.lastname: Ortiz Brüchle
authors.affiliation: Department of Pediatrics, Zagreb Medical School, University Hospital Center, Zagreb, Croatia.
authors.forename: Petra
authors.initials: P
authors.lastname: Grđan
authors.affiliation: Institute of Human Genetics, Medical Faculty, Uniklinik RWTH Aachen, Aachen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Zerres
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D011506:Proteins / Q000235:genetics*; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics* / Q000503:physiopathology*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C488620:SH3TC2 protein, human; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein
keywords: Axonal and demyelinating neuropathy; Distal weakness; Genetic modifier; SH3TC2 gene; SMN1 gene; Spinal muscular atrophy