Neuropediatrics 2012; 43 - VS11_07
DOI: 10.1055/s-0032-1307162

Charcot-Marie-Tooth type 2A2 and idiopathic intracranial hypertension coinciding in a 15-year old boy

O Schwartz 1, W Weimer 1, P Young 2, G Kurlemann 1
  • 1Universitätsklinikum Münster, Klinik und Poliklinik für Kinder- und Jugendmedizin, Allgemeine Pädiatrie, Münster, Germany
  • 2Universitätsklinikum Münster, Klinik und Poliklinik für Neurologie, Münster, Germany

Aims: As an infant and toddler our patient presented with malpositioned big toes and frequent falls.

Methods: Neurological exam as an adolescent revealed atrophy of intrinsic hand musculature and decreased sense of vibration in the lower extremities. Nerve conduction studies of the tibial nerve showed marked reduction of MCV at 28m/s as well as reduction of the amplitude. After sequencing of PMP22-, MPZ- and Cx32 genes ruled out pathogenic mutations, a sural nerve biopsy was performed. Onion bulb formation and signs of axonal degeneration were evident on electron microscopy. Consequently, we suspected our patient suffering from CMT type 2. Sequence analysis confirmed this suspicion unveiling the heterozygous mutation c.1090 C>T in exon 11 of the MFN2-gene. Ophthalmic exam to exclude optic atrophy showed prominent optic discs and minor congestion of retinal vessels.

Results: With an incidence of 1/100.000, CMT2A is the most common subtype of axonal Charcot-Marie-Tooth disease. Mutations of the MFN2-gene are found in 20% of CMT2 patients. CMT 2A2 is caused by a mutation in the mitofusin 2-gene located on chromosome 1p36.22. Its gene product, a dynamin-like GTPase in the outer mitochondrial membrane has important functions in fusion, calcium uptake and energy metabolism of mitochondria.

First symptoms usually occur during the first decade of life but late manifestations can become obvious until 30 years of age. Main symptoms are progressive weakness and atrophy of distal lower extremity muscles leading to stork leg appearance, bilateral foot drop, decreased or absent tendon jerk reflexes, mild sensory deficits and affection of intrinsic hand musculature in the course of the disease. Independent ambulation in adulthood is limited in more than 50% of patients who had disease onset under the age of 10 years. Scoliosis, optic atrophy, sensorineural hearing loss, vocal cord paralysis and involvement of the central nervous system have been observed in some patients. MFN2 mutations remain clinically silent in up to 25% of individuals.

Conclusion: Only supportive treatment is currently available.

CMT 2 - mitofusin - idiopathic intracranial hypertension