title: Excess of neuromuscular spindles in a fetus with Costello syndrome: a clinicopathological report.
abstract: The neuromuscular spindle (NMS) is a proprioceptive myofibrillar component of skeletal muscles that is necessary to maintain normal muscle tone and coordination. Recently, an excess of NMS has been reported as a congenital neuromuscular syndrome with a Noonan phenotype, now linked to Costello syndrome (CS). The vast majority of patients with CS have a de novo heterozygous mutation in the HRAS gene involved in the Ras/mitogen-activated protein kinase (MAPK) pathway. CS has many features in common with Noonan and cardiofaciocutaneous syndromes, also linked to activating mutations (but in other genes) of the Ras/MAPK pathway. This makes the orientation of molecular screening difficult. The observation of excess NMS in a 26-weeks'-gestation stillborn prompted us to screen the HRAS gene for mutation. The identification of a HRAS mutation made it possible to establish a diagnosis of CS. We conclude that the excess of NMS is the most reliable sign for the diagnosis of CS. Our findings also show the instrumental role of histological study of the skeletal muscles in the context of polyhydramnios and fetal hydrops.
authors.affiliation: Hôpital Intercommunal de Créteil, Créteil, France. martine.sinico@chicreteil.fr
authors.forename: Martine
authors.initials: M
authors.lastname: Sinico
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bassez
authors.forename: Claudine
authors.initials: C
authors.lastname: Touboul
authors.forename: Helene
authors.initials: H
authors.lastname: Cavé
authors.forename: Armand
authors.initials: A
authors.lastname: Vergnaud
authors.forename: Clément
authors.initials: C
authors.lastname: Zirah
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Fleury-Feith
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gettler
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Vojtek
authors.forename: Nicole
authors.initials: N
authors.lastname: Chevalier
authors.forename: Daniel
authors.initials: D
authors.lastname: Amram
authors.forename: Issam Abd
authors.initials: IA
authors.lastname: Alsamad
authors.forename: Bassam
authors.initials: B
authors.lastname: Haddad
authors.forename: Ferechté
authors.initials: F
authors.lastname: Encha-Razavi
mesh_terms: D056685:Costello Syndrome / Q000235:genetics / Q000473:pathology*; D005260:Female; D005333:Fetus; D006801:Humans; D009470:Muscle Spindles / Q000473:pathology*; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)