Excess of neuromuscular spindles in a fetus with Costello syndrome: a clinicopathological report.
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.
Sinico
Martine
M
Hôpital Intercommunal de Créteil, Créteil, France. martine.sinico@chicreteil.fr
Bassez
Guillaume
G
Touboul
Claudine
C
Cavé
Helene
H
Vergnaud
Armand
A
Zirah
Clément
C
Fleury-Feith
Jocelyne
J
Gettler
Sylvain
S
Vojtek
Anne Marie
AM
Chevalier
Nicole
N
Amram
Daniel
D
Alsamad
Issam Abd
IA
Haddad
Bassam
B
Encha-Razavi
Ferechté
F
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
C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)