title: Type 0 Spinal Muscular Atrophy: Further Delineation of Prenatal and Postnatal Features in 16 Patients.
abstract: 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.
  
  
  
  The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype.
  
  
  
  SMA patients with the 0SMN1/1SMN2 genotype were retrospectively collected using the UMD-SMN1 France database.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Genetics, Normandy Center for Medical Genomics and Personalized Medicine, Rouen University Hospital, Rouen, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Grotto
authors.affiliation: Department of Pediatric Neurology, Roger Salengro Hospital, Lille Regional University Hospital, Lille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuisset
authors.affiliation: Department of Pediatric Intensive Care, Rouen University Hospital, Rouen, France.|Inserm ERI 28, Institute for Research and Innovation in Biomedicine, Rouen University, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.affiliation: Department of Genetics, Robert Debre University Hospital, APHP, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Drunat
authors.affiliation: Inserm U1079, Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Faure
authors.affiliation: Department of Pediatrics and Genetics, Brest Regional University Hospital, Brest, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Audebert-Bellanger
authors.affiliation: Department of Pediatric Neurology, Necker-Enfants Malades Hospital, APHP, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.affiliation: Department of Pediatric Intensive Care, Le Mans Hospital, Le Mans, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Flurin
authors.affiliation: Department of Obstetrics and Gynecology, Saint-Brieuc Hospital, Saint-Brieuc, France.
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Grebille
authors.affiliation: Department of Genetics, Normandy Center for Medical Genomics and Personalized Medicine, Rouen University Hospital, Rouen, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Guerrot
authors.affiliation: Department of Genetics, Vannes Bretagne-Atlantique Hospital, Vannes, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Journel
authors.affiliation: Department of Genetics, Amiens University Hospital, Amiens, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Morin
authors.affiliation: Department of Genetics, Caen University Hospital, Caen, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Plessis
authors.affiliation: Department of Pediatric Intensive Care, Armand-Trousseau Children's Hospital, APHP, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Renolleau
authors.affiliation: Department of Genetics, Poissy-Saint-Germain-en-Laye Hospital, Poissy, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Roume
authors.affiliation: Department of Genetics, Versailles Hospital, Le Chesnay, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Simon-Bouy
authors.affiliation: Department of Genetics, Saint-Etienne University Hospital, Saint-Priest-en-Jarez, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.affiliation: Department of Genetics, Necker-Enfants Malades Hospital, APHP, Paris, France.
authors.forename: Marjolaine
authors.initials: M
authors.lastname: Willems
authors.affiliation: Department of Genetics, Normandy Center for Medical Genomics and Personalized Medicine, Rouen University Hospital, Rouen, France.|Inserm U1079, Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.affiliation: Department of Obstetrics and Gynecology, Rouen University Hospital, Rouen, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Verspyck
authors.affiliation: Department of Genetics, Normandy Center for Medical Genomics and Personalized Medicine, Rouen University Hospital, Rouen, France.|Inserm U1079, Institute for Research and Innovation in Biomedicine, Rouen University, Rouen, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Saugier-Veber
mesh_terms: D001176:Arthrogryposis / Q000209:etiology / Q000503:physiopathology*; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D003389:Cranial Nerve Diseases / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D005838:Genotype; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008017:Life Expectancy; D008297:Male; D009123:Muscle Hypotonia / Q000209:etiology / Q000503:physiopathology*; D012021:Reflex, Abnormal; D012127:Respiratory Distress Syndrome, Newborn / Q000209:etiology / Q000503:physiopathology*; D014897:Spinal Muscular Atrophies of Childhood / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics; D016216:Ultrasonography, Prenatal
chemical_list: C526471:SMN1 protein, human; C526477:SMN2 protein, human; D055533:Survival of Motor Neuron 1 Protein; D055540:Survival of Motor Neuron 2 Protein
keywords: Spinal muscular atrophy; congenital heart defect; fetal akinesia deformation sequence; human SMN2 protein; prenatal ultrasonography