Charcot-Marie-Tooth, dominant intermediate E (CMT-DIE/MIM#614455), is due to inverted formin 2 (INF2) mutations. INF2 is involved to form linear polymers of actin.

33 patients with INF2 mutations were reported as associating CMT and focal segmental glomerulosclerosis (FSGS).

We collected data from clinical records and applied a next generation sequencing approach.

Patient 1 (P1), a 33-years-old woman, presented limited motor acquisitions during infancy and renal failure during adolescence.

Patient 2 (P2), a 54-years-old man, developed during adolescence progressive balance impairment and cramps with nephrotic-range proteinuria.

For both patients the family history was unremarkable and clinical examination showed distal paresis with amyotrophy, areflexia, and severe sensory impairment.

For P1:

Nerve conduction study (NCS) showed on median nerve (right/left): distal motor latency (DML): 6.2/5.9 ms, distal compound motor action potential (CMAP) amplitude: 0.9/1.6 mV and velocity: 21/26.2 m/s, and on ulnar nerves: 4.0/4.2, 1.7/1.6, 32.5/33.7.

Audiometry demonstrated a loss of perception in high frequencies.

Lumbar magnetic imaging resonance revealed a major roots hypertrophy.

Sural nerve biopsy showed a marked loss of myelinated axons and cluster of regeneration.

Renal biopsy was uninformative and a kidney transplant was performed at the age of 17.

For P2:

NCS showed on right median nerve: DML: 5.2 ms, distal CMAP amplitude: 12 mV and velocity: 29.1 m/s and on tibial posterior nerves (right/left):  11.5/10, 0.5/2.0, 22.5/24.

Renal biopsy showed a FSGS evolving to end-stage renal disease at the age of 18.

Genetic investigations revealed the heterozygous INF2 mutations, for P1: c.217G>C p.(Gly73Arg) (unpublished) and for P2: c.341G>A p.(Gly114Asp).

We describe two additional cases of CMT-DIE combined with end-stage nephropathy, one being a FSGS. Roots hypertrophy was identified as a novel clinical feature. To date it remains unsolved why some CMT patients present this peculiar finding.