Single Center Experience of RETREG1-related Hereditary Sensory Autonomic Neuropathy in Turkey
Arman Cakar1, Gulandam Bagirova2, Hacer Durmus1, Zehra Oya Uyguner2, Fatma Yesim Parman1
1Neuromuscular Unit, Neurology Department, Istanbul Faculty of Medicine, Istanbul University, 2Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University
Objective:
To describe the clinical characteristics of patients with RETREG1 mutations.
Background:
Homozygous loss-of-function mutations in RETREG1 result in Hereditary Sensory Autonomic Neuropathy (HSAN) Type 2. Clinical features include variable autonomic disturbances and upper motor neuron features such as brisk tendon reflexes, spasticity, and Babinski sign.
Design/Methods:
Herein, we evaluated the clinical and genetic features of 6 patients from 3 unrelated families with RETREG1 mutation at the Neuromuscular Unit of the Istanbul Faculty of Medicine, Istanbul University.
Results:
Four patients were male. The median age of onset was 7.0 ± 2.5 (between 2 and 9 years). Foot ulcerations were the presenting symptom in four patients and walking difficulties in two. All patients were born to consanguineous marriages. In a median disease duration of 23.0 ± 14.4 years, four patients had osteomyelitis, and two had toe amputations. Five patients had a history of painless fractures in different lower extremity bones. Four patients had autonomic nervous system symptoms such as excessive sweating, constipation and orthostatism. Neurological examination of all patients showed spasticity, and brisk tendon reflexes. Muscle weakness in the lower extremities was noted in five patients. Sensory examination showed stocking type hypoesthesia and diminished vibration sensation in all patients. Five patients had pes planus deformity. Nerve conduction studies showed axonal sensory neuropathy in four patients and sensory-motor in two. Two families had homozygous c.433C>T (p.Gln145*), and one had c.826delA (p.S276VfsX8) pathogenic variants in the RETREG1 gene.
Conclusions:
In our study, all patients showed signs and symptoms consistent with pain insensitivity. Although shadowed by marked sensory symptoms, motor signs, such as spasticity, and muscle weakness, were also noted in our patients. Considering the autosomal recessive inheritance, new cases with RETREG1 mutation are likely to be reported from Turkey, a country with a high rate of consanguineous marriages.