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Long-term observations of patients with infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1)
S Rudnik-Schöneborn1, P Stolz, R Varon
1Institute for Human Genetics, Aachen University of Technology, Aachen, Germany. srudnik-schoeneborn@ukaachen.de
Insights
This study reports on 6 infants with spinal muscular atrophy with respiratory distress type 1 (SMARD1) who survived for years with mechanical ventilation. Diagnosis was confirmed by IGHMBP2 gene mutations, revealing prolonged survival and new symptoms like voiding dysfunction.
Area of Science:
- Genetics
- Neurology
- Pediatrics
Background:
- Infantile spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a severe genetic neuromuscular disorder.
- Typically, SMARD1 presents with rapid progression and poor prognosis.
Observation:
- Six unrelated patients with SMARD1 experienced prolonged survival (4.5-11 years) with mechanical ventilation.
- Onset occurred within the first two months, characterized by hypotonia, failure to thrive, and respiratory distress.
- Patients developed diaphragmatic palsy, distal muscular atrophy, joint contractures, and hand drops.
Findings:
- Biallelic IGHMBP2 gene mutations confirmed SMARD1 in all patients.
- New observations include voiding dysfunction with reflux nephropathy and autonomic nerve dysfunction (cardiac arrhythmia, hypertension, excessive sweating).
- Muscle atrophy was more pronounced distally, with evidence of peripheral nerve involvement.
Implications:
- This study expands the understanding of SMARD1, demonstrating potential for prolonged survival with ventilatory support.
- The findings highlight novel clinical manifestations, including urological and autonomic dysfunction, in SMARD1 patients.
- Further research into IGHMBP2 gene function and therapeutic strategies for SMARD1 is warranted.
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.
