136 Coincidential hydrocephalus in twins with CMT1X


The association of CMT1X with white matter abnormalities and "stroke like episodes" has long been recognised, and a recent review of the 133 patients with CMT1X in our cohort found that 10/26 MRI brain scans showed white matter abnormalities.(1) The literature describes very occasional patients who have any type of CMT and hydrocephalus.


A pair of monozygotic twins have the p.Trp24Cys GJB1 mutation which segregates with CMT in their family, with recognised phenotypic variability in the women, attributable to X-inactivation. One of the twins presented in their 20’s with headache and visual obscurations due to hydrocephalus resulting from decompensation of a previously diagnosed aqueductal stenosis. The second twin had migraine at age 27, an MRI identified lateral and third ventricular dilatation due to focal narrowing with an aqueductal web. An endoscopic third ventriculocysternostomy was performed. An affected cousin with the family GJB1 mutation has normal brain imaging.


Despite the finding of hydrocephalus in both affected twins, further family evaluation confirmed the hydrocephalous not to segregate with the GJB1 mutation. This highlights the importance of detailed phenotype segregation studies before diagnosing an atypical phenotype with genetic diseases. Alterna- tive genetic causes for the hydrocephalus are being sought.

1) Vivekanandam V, Hoskote C, Rossor AM, Reilly MM. CNS phenotype in X linked Charcot- Marie-Tooth disease. J Neurol Neurosurg Psychiatry 2018 Dec 5;90(9).

carolynnedoherty@doctors.org.uk|NIHR Bursary