Sarah Grotto1, Jean-Marie Cuisset2, Stéphane Marret3,4, Séverine Drunat5, Patricia Faure6, Séverine Audebert-Bellanger7, Isabelle Desguerre8, Vincent Flurin9, Anne-Gaëlle Grebille10, Anne-Marie Guerrot1, Hubert Journel11, Gilles Morin12, Ghislaine Plessis13, Sylvain Renolleau14, Joëlle Roume15, Brigitte Simon-Bouy16, Renaud Touraine17, Marjolaine Willems18, Thierry Frébourg1,6, Eric Verspyck19, Pascale Saugier-Veber1,6. 1. Department of Genetics, Normandy Center for Medical Genomics and Personalized Medicine, Rouen University Hospital, Rouen, France. 2. Department of Pediatric Neurology, Roger Salengro Hospital, Lille Regional University Hospital, Lille, France. 3. Department of Pediatric Intensive Care, Rouen University Hospital, Rouen, France. 4. Inserm ERI 28, Institute for Research and Innovation in Biomedicine, Rouen University, France. 5. Department of Genetics, Robert Debre University Hospital, APHP, Paris, France. 6. Inserm U1079, Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France. 7. Department of Pediatrics and Genetics, Brest Regional University Hospital, Brest, France. 8. Department of Pediatric Neurology, Necker-Enfants Malades Hospital, APHP, Paris, France. 9. Department of Pediatric Intensive Care, Le Mans Hospital, Le Mans, France. 10. Department of Obstetrics and Gynecology, Saint-Brieuc Hospital, Saint-Brieuc, France. 11. Department of Genetics, Vannes Bretagne-Atlantique Hospital, Vannes, France. 12. Department of Genetics, Amiens University Hospital, Amiens, France. 13. Department of Genetics, Caen University Hospital, Caen, France. 14. Department of Pediatric Intensive Care, Armand-Trousseau Children's Hospital, APHP, Paris, France. 15. Department of Genetics, Poissy-Saint-Germain-en-Laye Hospital, Poissy, France. 16. Department of Genetics, Versailles Hospital, Le Chesnay, France. 17. Department of Genetics, Saint-Etienne University Hospital, Saint-Priest-en-Jarez, France. 18. Department of Genetics, Necker-Enfants Malades Hospital, APHP, Paris, France. 19. Department of Obstetrics and Gynecology, Rouen University Hospital, Rouen, France.
Abstract
BACKGROUND: Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0SMN1/1SMN2 genotype, the most severe genotype compatible with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset. OBJECTIVE: The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype. METHODS: SMA patients with the 0SMN1/1SMN2 genotype were retrospectively collected using the UMD-SMN1 France database. RESULTS: Data from 16 patients were reviewed. These 16 patients displayed type 0 SMA. At birth, a vast majority had profound hypotonia, severe muscle weakness, severe respiratory distress, and cranial nerves involvement (inability to suck/swallow, facial muscles weakness). They showed characteristics of fetal akinesia deformation sequence and congenital heart defects. Recurrent episodes of bradycardia were observed. Death occurred within the first month. At prenatal stage, decreased fetal movements were frequently reported, mostly only by mothers, in late stages of pregnancy; increased nuchal translucency was reported in about half of the cases; congenital heart defects, abnormal amniotic fluid volume, or joint contractures were occasionally reported. CONCLUSION: Despite a prenatal onset attested by severity at birth and signs of fetal akinesia deformation sequence, prenatal manifestations of type 0 SMA are not specific and not constant. As illustrated by the frequent association with congenital heart defects, type 0 SMA physiopathology is not restricted to motor neuron, highlighting that SMN function is critical for organogenesis.
BACKGROUND:Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0SMN1/1SMN2 genotype, the most severe genotype compatible with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset. OBJECTIVE: The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype. METHODS: SMA patients with the 0SMN1/1SMN2 genotype were retrospectively collected using the UMD-SMN1 France database. RESULTS: Data from 16 patients were reviewed. These 16 patients displayed type 0 SMA. At birth, a vast majority had profound hypotonia, severe muscle weakness, severe respiratory distress, and cranial nerves involvement (inability to suck/swallow, facial muscles weakness). They showed characteristics of fetal akinesia deformation sequence and congenital heart defects. Recurrent episodes of bradycardia were observed. Death occurred within the first month. At prenatal stage, decreased fetal movements were frequently reported, mostly only by mothers, in late stages of pregnancy; increased nuchal translucency was reported in about half of the cases; congenital heart defects, abnormal amniotic fluid volume, or joint contractures were occasionally reported. CONCLUSION: Despite a prenatal onset attested by severity at birth and signs of fetal akinesia deformation sequence, prenatal manifestations of type 0 SMA are not specific and not constant. As illustrated by the frequent association with congenital heart defects, type 0 SMA physiopathology is not restricted to motor neuron, highlighting that SMN function is critical for organogenesis.
Authors: Gillian K Maxwell; Eva Szunyogova; Hannah K Shorrock; Thomas H Gillingwater; Simon H Parson Journal: J Anat Date: 2018-02-22 Impact factor: 2.610
Authors: Marianna A Maretina; Galina Y Zheleznyakova; Kristina M Lanko; Anna A Egorova; Vladislav S Baranov; Anton V Kiselev Journal: Curr Genomics Date: 2018-08 Impact factor: 2.236
Authors: Noémi Dahan-Oliel; Sarah Cachecho; Douglas Barnes; Tanya Bedard; Ann M Davison; Klaus Dieterich; Maureen Donohoe; Alicja Fąfara; Reggie Hamdy; Helgi T Hjartarson; Naimisha S Hoffman; Eva Kimber; Igor Komolkin; Ruth Lester; Eva Pontén; Harold J P van Bosse; Judith G Hall Journal: Am J Med Genet C Semin Med Genet Date: 2019-07-07 Impact factor: 3.908