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New observations on minifascicular neuropathy with sex-dependent gonadal dysgenesis: a case series with nerve ultrasound assessment

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Abstract

Background

Gonadal dysgenesis with minifascicular neuropathy (GDMN) is a rare autosomal recessive condition associated with biallelic DHH pathogenic variants. In 46, XY individuals, this disorder is characterized by an association of minifascicular neuropathy (MFN) and gonadal dysgenesis, while in 46, XX subjects only the neuropathic phenotype is present. Very few patients with GDMN have been reported so far. We describe four patients with MFN due to a novel DHH likely pathogenic homozygous variant and the results of nerve ultrasound assessment.

Methods

This retrospective observational study included 4 individuals from 2 unrelated Brazilian families evaluated for severe peripheral neuropathy. Genetic diagnosis was performed with a peripheral neuropathy next-generation sequencing (NGS) panel based on whole exome sequencing focused analysis that included a control SRY probe to confirm genetic sex. Clinical characterization, nerve conduction velocity studies, and high-resolution ultrasound nerve evaluation were performed in all subjects.

Results

Molecular analysis disclosed in all subjects the homozygous DHH variant p.(Leu335Pro). Patients had a striking phenotype, with marked trophic changes of extremities, sensory ataxia, and distal anesthesia due to a sensory-motor demyelinating polyneuropathy. One 46, XY phenotypically female individual had gonadal dysgenesis. High-resolution nerve ultrasound showed typical minifascicular formation and increased nerve area in at least one of the nerves assessed in all patients.

Conclusion

Gonadal dysgenesis with minifascicular neuropathy is a severe autosomal recessive neuropathy characterized by trophic alterations in limbs, sensory ataxia, and distal anesthesia. Nerve ultrasound studies are very suggestive of this condition and may help to avoid invasive nerve biopsies.

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Data Availability

All data will be made available upon request.

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Authors and Affiliations

  1. Neuromuscular Unit of Neurology Department From Hospital Geral de Fortaleza, Ceará, Brazil

    Lara Albuquerque Brito, Hermany Capistrano Freitas & Cleonisio Leite Rodrigues

  2. Department of Neurology, Faculdade de Medicina, Universidade Federal Do Ceará, Fortaleza, Brazil

    Paulo Ribeiro Nóbrega

  3. Department of Neurology, Faculdade de Medicina, Universidade de São Paulo (FMUSP), São Paulo, Brazil

    Paulo Ribeiro Nóbrega & Fernando Kok

  4. Department of Radiology, Faculdade de Medicina, Universidade Federal Do Ceará, Fortaleza, Brazil

    Daniel Aguiar Dias & André Rodrigues Façanha Barreto

  5. Clinical Neurophysiology of Neurology Department From Hospital Geral de Fortaleza, Ceará, Brazil

    Hermany Capistrano Freitas & Cleonisio Leite Rodrigues

  6. Mendelics Genomic Analysis, Sao Paulo, Brazil

    Fernando Kok

Authors
  1. Lara Albuquerque Brito
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  2. Paulo Ribeiro Nóbrega
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  4. André Rodrigues Façanha Barreto
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Contributions

Lara Albuquerque de Brito: conceptualization (lead), data curation (lead), formal analysis (equal), investigation (equal), supervision (equal), project administration (lead), writing—original draft (lead), and writing—review and editing (equal). Paulo Ribeiro Nóbrega: conceptualization (equal), data curation (equal), formal analysis (equal), investigation (equal), supervision (lead), writing—original draft (equal), and writing—review and editing (lead). Daniel Aguiar Dias: data curation (equal), investigation (equal), visualization (equal), and writing—review and editing (equal). André Rodrigues Façanha Barreto: data curation (equal), investigation (equal), visualization (equal), and writing—review and editing (equal). Hermany Capistrano Freitas: data curation (equal), investigation (equal), visualization (equal), and writing—review and editing (equal). Fernando Kok: data curation (equal), formal analysis (equal), investigation (equal), supervision (equal), and writing—review and editing (equal). Cleonisio Leite Rodrigues: conceptualization (equal), data curation (equal), formal analysis (equal), investigation (equal), supervision (equal), and writing—review and editing (equal).

Corresponding author

Correspondence to Paulo Ribeiro Nóbrega.

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The research has been approved by the local ethics committee under the number 5.802.295. 

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Brito, L.A., Nóbrega, P.R., Dias, D.A. et al. New observations on minifascicular neuropathy with sex-dependent gonadal dysgenesis: a case series with nerve ultrasound assessment. Neurol Sci 44, 3691–3696 (2023). https://doi.org/10.1007/s10072-023-06792-y

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