Sibling Cases of Charcot-Marie-Tooth Disease Type 4H with a Homozygous FGD4 Mutation and Cauda Equina Thickening

Abstract

Charcot-Marie-Tooth disease type 4H (CMT4H) is an autosomal recessive inherited demyelinating neuropathy caused by an FYVE, RhoGEF, and a PH domain-containing protein 4 (FGD4) gene mutation. CMT4H is characterized by an early onset, slow progression, scoliosis, distal muscle atrophy, and foot deformities. We herein present sibling cases of CMT4H with a homozygous mutation in the FGD4 gene. Both patients exhibited cauda equina thickening on magnetic resonance imaging, which had not been reported among the previous CMT4H cases. This is the first report of CMT4H with a homozygous FGD4 c.1730G>A (p.Arg577Gln) mutation showing mild progression and cauda equina thickening.

Keywords: Charcot-Marie-Tooth disease type 4H; FGD4; autosomal recessive; cauda equina thickening.

Figure 1.

The pedigree of the present family carrying the FGD4 gene mutation is shown. There was consanguinity between the parents of Patients 1 and 2.

Figure 2.

Photographs of characteristic foot deformities of patienst 1 and 2 are shown. Patient 1 showed pes cavus and hammer toes with distal atrophy of lower limbs (A and B). Patient 2 showed more severe foot deformities than Patient 1 (C and D).

Figure 3.

Skeletal muscle CT image of Patient 1 at the slices of the upper arm level (A), the forearm level (B), the thigh level (C) and the calf level (D) showed symmetrical distal dominant muscle atrophy with fatty degeneration.

Figure 4.

Lumbar spinal MRI of Patient 1 shows a prominent thickening of the cauda equina on T2-weighted sagittal (A), short tau inversion recovery (STIR) coronal (B) and T2-weighted axial (C) images. A lumbar spinal MRI of Patient 2 shows similar findings of cauda equina thickening with multiple disc herniation on T2-weighted sagittal (D), STIR coronal (E) and T2-weighted axial (F) images.

Figure 5.

Direct sequencing of polymerase chain reaction products amplified from the exon 14 region of the FGD4 gene of patients 1 and 2 revealed a homozygous c.1730G>A (p.Arg577Gln) mutation. The arrow indicates the position of the missense mutation.