Michela Catteruccia is an experienced Neurologist that works at the Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome. She is particularly involved in the follow up of patients affected by 5q linked SMA and in other motor neuron disorders of childhood.
This poster was presented as part of the EURO-NMD 1st Annual Meeting - Freiburg, Germany in November, 2017.
Contact Michela Catteruccia about this poster at firstname.lastname@example.org.
Michela Catteruccia, Fabiana Fattori, Adele D’Amico, Enrico Bertini
Unit of Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
Background: spinal muscular atrophy with lower extremity predominance (SMA-LED) is characterized by congenital or early childhood onset motor neuron degeneration with lower limbs predominant weakness.
Methods: we examined patients with a phenotype suggestive for motor neuronopathy predominantly affecting the lower limbs were identified and referred for molecular diagnosis by Next-Generation Sequencing (NGS) panel including the following genes ASAH1; BICD2 ; DYNC1H1; EGR2; FIG4 ; GARS ; GDAP1; GJB1; HSN2; HSPB1; HSPB8; KIAA1985; LITAF; MFN2; PMP22; IGHMBP2; TBCE ; TRPV4.
Results: We report on 15 patients (11 males, 4 females) from 15 different families and characterized by congenital or childhood-onset lower limb wasting and weakness. All patients were sporadic cases. Clinical severity ranged from lower legs arthrogryposis to mild and non-progressive lower limb weakness. One patient had also epilepsy. Four patients underwent brain MRI 4/9 that revealed in one case a polymicrogyric pattern. ENG/EMG showed in all patients a neurogenic pattern of chronic denervation with reduced CMAP. Muscle biopsy was performed in 3/9 and showed neurogenic features. Seven patients underwent muscle MRI that showed in 5/6 a characteristic pattern of involvement of the thigh and the lower leg muscles. Molecular analysis showed that 3/15 had mutations in DYHC1H1, 2/15 a mutation in BICD2, 1/15 a mutation in SETX, 1/15 a mutation in TRPV4, 1/15 a mutation in GDAP1, 1/15 a mutation in FIG4, 2/15 were mutated in IGHMBP2. In 4/15 patients no mutations were identified.
By WES we characterized a new disease gene TBCE related to a motor neuron disease associated with a spastic ataxic syndrome of infantile onset in 5 patients out of 4 families.
Conclusion: Our findings further expands clinical and mutational spectra of SMA-LED. Although the cohort is not large, our data suggest that in well characterized patients, the diagnostic yield of our molecular test is over 70%.