Phenotypic features of RETREG1-related hereditary sensory autonomic neuropathy.
genetic
novel
pain
polyneuropathy
variant
Journal
Journal of the peripheral nervous system : JPNS
ISSN: 1529-8027
Titre abrégé: J Peripher Nerv Syst
Pays: United States
ID NLM: 9704532
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
revised:
10
07
2023
received:
14
04
2023
accepted:
11
07
2023
medline:
7
9
2023
pubmed:
14
7
2023
entrez:
14
7
2023
Statut:
ppublish
Résumé
Homozygous loss-of-function mutations in the RETREG1 gene result in Hereditary Sensory Autonomic Neuropathy Type 2B. Clinical features include pain loss, autonomic disturbances, and upper motor neuron features. We evaluated the clinical and genetic features of seven patients from four families with RETREG1 variants. Five patients were male. The median age of disease onset was 7.00 ± 2.81 (between 2 and 10 years). A combination of painless wounds, trophic changes, and foot ulcerations was the presenting symptom in five patients and walking difficulties in two. Motor symptoms were present in five patients. In a median disease duration of 30.00 ± 12.88 years, five patients had osteomyelitis, and three had toe amputations. A history of renal disease was present in one family. In another family, three affected siblings had short stature and a history of delayed puberty. Although sensory signs predominated the clinical findings, various degrees of motor signs such as muscle weakness, spasticity, and brisk tendon reflexes were noted in all patients. Nerve conduction studies showed axonal sensory-motor neuropathy in five patients and sensory neuropathy in two. Three pathogenic variants were identified in the RETREG1 gene. Two unrelated patients had a homozygous c.433C > T/p.(Gln145*), one a homozygous c.826delA/p.(Ser276Valfs*8), and the last had a novel homozygous c.102delC/p.(Ala35Glnfs*349) variants. In our study, all patients showed signs and symptoms consistent with pain insensitivity. Although shadowed by sensory symptoms, motor signs were noted in our patients. Further studies are necessary to clarify the causal relationship between extra-neurological features and RETREG1 mutations.
Sections du résumé
BACKGROUND AND AIMS
Homozygous loss-of-function mutations in the RETREG1 gene result in Hereditary Sensory Autonomic Neuropathy Type 2B. Clinical features include pain loss, autonomic disturbances, and upper motor neuron features.
METHODS
We evaluated the clinical and genetic features of seven patients from four families with RETREG1 variants.
RESULTS
Five patients were male. The median age of disease onset was 7.00 ± 2.81 (between 2 and 10 years). A combination of painless wounds, trophic changes, and foot ulcerations was the presenting symptom in five patients and walking difficulties in two. Motor symptoms were present in five patients. In a median disease duration of 30.00 ± 12.88 years, five patients had osteomyelitis, and three had toe amputations. A history of renal disease was present in one family. In another family, three affected siblings had short stature and a history of delayed puberty. Although sensory signs predominated the clinical findings, various degrees of motor signs such as muscle weakness, spasticity, and brisk tendon reflexes were noted in all patients. Nerve conduction studies showed axonal sensory-motor neuropathy in five patients and sensory neuropathy in two. Three pathogenic variants were identified in the RETREG1 gene. Two unrelated patients had a homozygous c.433C > T/p.(Gln145*), one a homozygous c.826delA/p.(Ser276Valfs*8), and the last had a novel homozygous c.102delC/p.(Ala35Glnfs*349) variants.
INTERPRETATION
In our study, all patients showed signs and symptoms consistent with pain insensitivity. Although shadowed by sensory symptoms, motor signs were noted in our patients. Further studies are necessary to clarify the causal relationship between extra-neurological features and RETREG1 mutations.
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
351-358Informations de copyright
© 2023 Peripheral Nerve Society.
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