Type 0 Spinal Muscular Atrophy (SMA) is the most severe manifestation of SMA[1]. The designation of “type 0” indicates the onset of SMA symptoms occurred before birth.[2] Expectant mothers frequently will report decreased fetal movement.[3] Prenatal imaging may reveal fetal akinesia, increased abnormal amniotic fluid volume, increased nuchal tube translucency, congenital heart defects, or joint contractures.[3] Prenatal demise can occur in type 0 SMA.[4]
The newborn with type 0 SMA presents with severe hypotonia (or may lack appreciable tone altogether), severe weakness)or paralysis in all muscle groups including bulbar and facial muscles, absent reflexes, and respiratory distress requiring rapid introduction of external ventilation.[1] [2] [3] Features of the fetal hypokinesia deformation sequence consisting of intrauterine growth restriction, arthrogryposes, dysmorphic facies, and pulmonary hypoplasia are usually present at birth.[3] [6] Infants with type 0 SMA will have poor or absent ability to suck and swallow, require mechanical ventilation due to poor respiratory effort, and will experience frequent episodes of bradycardia along with a higher than predicted incidence of cardiac defects.[3]
Electrophysiology studies performed in infants with type 0 SMA may reveal total inability to excite motor nerves, or reduced spontaneous activity, reduced compound motor action potentials, and an absent F-wave.[7] [8] Genetic testing of the patient with type 0 SMA should confirm two pathogenic variants in the Survival Motor Neuron (SMN) 1 genes, and typically reveals only one copy of the putatively protective SMN2 gene.[9]
A diagnosis of type 0 SMA conveys the poorest prognosis amongst SMA patients. Infants with type 0 SMA do not experience improvements in tone nor strength, nor are they expected to make developmental progress.[1] [2] [5] Death due to respiratory complications occurs within weeks of birth, and survival beyond six months of age has not been observed.[2] [5]
References
1. Kolb SJ, Kissel JT. Spinal Muscular Atrophy. Neurologic clinics. 2015;33(4):831-846.
2. Dubowitz V. Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. Eur J Paediatr Neurol. 1999;3(2):49-51.
3. Grotto S, Cuisset JM, Marret S, et al. Type 0 Spinal Muscular Atrophy: Further Delineation of Prenatal and Postnatal Features in 16 Patients. J Neuromuscul Dis. 2016;3(4):487-495.
4. Tizzano E. Spinal muscular atrophy during human development: where are the early pathogenic findings? Adv Exp Med Biol. 2009;652:225-235.
5. MacLeod MJ, Taylor JE, Lunt PW, Mathew CG, Robb SA. Prenatal onset spinal muscular atrophy. Eur J Paediatr Neurol. 1999;3(2):65-72.
6. Gonzalez De Dios J, Martinez Frias ML, Arroyo Carrera I, et al. [Role of signs of fetal hypokinesia in the diagnosis of spinal muscular atrophy of neonatal onset]. Anales espanoles de pediatria. 2002;56(3):233-240.
7. Yuan P, Jiang L. Clinical characteristics of three subtypes of spinal muscular atrophy in children. Brain Dev. 2015;37(5):537-541.
8. Korinthenberg R, Sauer M, Ketelsen UP, et al. Congenital axonal neuropathy caused by deletions in the spinal muscular atrophy region. Ann Neurol. 1997;42(3):364-368.
9. Butchbach ME. Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases. Frontiers in molecular biosciences. 2016;3:7.