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

• Published in: Neurological sciences Vol. 44; no. 10; pp. 3691 - 3696
• Main Authors: Brito, Lara Albuquerque, Nóbrega, Paulo Ribeiro, Dias, Daniel Aguiar, Barreto, André Rodrigues Façanha, Freitas, Hermany Capistrano, Kok, Fernando, Rodrigues, Cleonisio Leite
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-10-2023; Springer Nature B.V
• Subjects: Anesthesia; Ataxia; Biopsy; Demyelination; Genetic screening; Gonadal dysgenesis; Medicine; Medicine & Public Health; Nerve conduction; Neurology; Neuroradiology; Neurosciences; Neurosurgery; Next-generation sequencing; Original Article; Peripheral neuropathy; Phenotypes; Polyneuropathy; Psychiatry; Ultrasonic imaging; Ultrasound; Polyneuropathy; 46, XY gonadal dysgenesis, partial, with minifascicular neuropathy; Hedgehog proteins
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-023-06792-y

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.