Abstract Details

Title Central Nervous System Involvement in HINT1 Neuropathy: An Overlooked Phenotypical Feature?

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P8 - Poster Session 8 (11:45 AM-12:45 PM)

Poster/Presentation
Number 11-001

Objective To investigate the central nervous system involvement in histidine triad nucleotide-binding protein 1 (HINT1) mutations.

Background

Biallelic mutations in the HINT1 gene cause autosomal recessive Charcot-Marie-Tooth type 2 (AR-CMT2). Neuromyotonia is a striking feature of this disease and present in about 80% of the patients. HINT1 is widely expressed in the central nervous system (CNS). On the other hand, the frequency of CNS symptoms is currently unknown.

Design/Methods Herein, we evaluated the clinical and genetic features of 13 patients from 8 unrelated families with HINT1 mutation. CNS involvement was defined by medical history in all patients. Appropriate diagnostic tests, such as cranial MRI and electroencephalography (EEG), were performed depending on clinical necessities.

Results Seven patients were female. The mean age of onset was 12,30 ± 6,30 (between 5 and 25 years). The most common presenting symptom was distal weakness and atrophy in the lower limbs (10/13 patients). Sensory symptoms were present in 4 patients. Eleven patients were born to consanguineous marriages. Regarding the CNS symptoms, five patients from three non-consanguineous families had febrile seizures. Of these, 4 also had intellectual disability defined by either poor academic performance or IQ test. Cranial MRI was performed in two patients and did not show any significant abnormalities. EEG showed generalized slow waves in one patient. Cerebrospinal fluid (CSF) analysis was performed in 2 patients did not reveal any significant abnormalities. Whole-exome sequencing data of two non-consanguineous patients were analyzed for genes associated with febrile seizures, and no pathogenic variants were found.

Conclusions

High frequency of intellectual disability and febrile seizures in our patients suggests that CNS involvement may be a part of the phenotypical spectrum of HINT1 mutation. Symptoms and signs related to the peripheral nervous system are well-defined; on the other hand, prospective studies from different cohorts are necessary to define the characteristics of CNS involvement.

Authors/Disclosures
Arman Cakar PRESENTER	Arman Cakar has nothing to disclose.
	No disclosure on file
Ayse Candayan	Ayse Candayan has nothing to disclose.
Serdar Ceylaner	Serdar Ceylaner has nothing to disclose.
Esra Battaloglu	Esra Battaloglu has nothing to disclose.
Hacer Durmus, MD (Department of Neurology, Istanbul Faculty of Medicine)	Dr. Durmus has nothing to disclose.
Fatma Yesim Parman, MD (Istanbul Üniversitesi Tip Fakültesi)	Dr. Parman has nothing to disclose.

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