title: Long-term observations of patients with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1).
abstract: We describe 6 unrelated patients affected by infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1) with prolonged survival upon mechanical ventilation (4.5-11 years), which has not been reported before. Biallelic mutations in the IGHMBP2 gene proved the diagnosis of SMARD1 in all patients. Disease onset was in the first 2 months in the described patients, starting with generalised hypotonia, failure to thrive, and early breathing difficulties. Diaphragmatic palsy was diagnosed and permanent ventilation was initiated 2-8 months after onset. Within months a more distal muscular atrophy became evident associated with joint contractures (talipes), hand drops, and fatty finger pads. Motor development remained minimal, loss of function was observed within the first year after which no further progression was recorded. Voiding dysfunction with reflux nephropathy was observed in 3 patients and has not been reported before. Further evidence of autonomic nerve dysfunction resulting in cardiac arrhythmia, hypertension, and excessive sweating was given in 2 patients. Investigative results were largely compatible with those obtained in classic SMA. However, neurogenic atrophy muscle was more pronounced in distal muscles, if examined, and there was evidence of peripheral nerve involvement at least in some patients.
authors.affiliation: Institute for Human Genetics, Aachen University of Technology, Aachen, Germany. srudnik-schoeneborn@ukaachen.de
authors.forename: S
authors.initials: S
authors.lastname: Rudnik-Schöneborn
authors.forename: P
authors.initials: P
authors.lastname: Stolz
authors.forename: R
authors.initials: R
authors.lastname: Varon
authors.forename: K
authors.initials: K
authors.lastname: Grohmann
authors.forename: M
authors.initials: M
authors.lastname: Schächtele
authors.forename: U-P
authors.initials: UP
authors.lastname: Ketelsen
authors.forename: D
authors.initials: D
authors.lastname: Stavrou
authors.forename: H
authors.initials: H
authors.lastname: Kurz
authors.forename: C
authors.initials: C
authors.lastname: Hübner
authors.forename: K
authors.initials: K
authors.lastname: Zerres
mesh_terms: D000367:Age Factors; D002657:Child Development; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D012133:Respiratory Paralysis / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D014897:Spinal Muscular Atrophies of Childhood / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C489892:IGHMBP2 protein, human; D014157:Transcription Factors