Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population

• Published in: Annals of clinical and translational neurology Vol. 8; no. 6; pp. 1260 - 1268
• Main Authors: Greenbaum, Lior, Ben‐David, Merav, Nikitin, Vera, Gera, Orna, Barel, Ortal, Hersalis‐Eldar, Adi, Shamash, Jana, Shimshoviz, Noam, Reznik‐Wolf, Haike, Shohat, Mordechai, Dominissini, Dan, Pras, Elon, Dori, Amir
• Format: Journal Article
• Language: English
• Published: United States John Wiley and Sons Inc 01.06.2021; Wiley
• Subjects: Adult; Charcot-Marie-Tooth Disease - ethnology; Charcot-Marie-Tooth Disease - genetics; Charcot-Marie-Tooth Disease - pathology; Charcot-Marie-Tooth Disease - physiopathology; Cross-Sectional Studies; Electrodiagnosis; Female; Heat-Shock Proteins - genetics; Humans; Iran - ethnology; Jews - genetics; Male; Middle Aged; Molecular Chaperones - genetics; Retrospective Studies; Ultrasonography; Iran
• ISSN: 2328-9503; 2328-9503
• DOI: 10.1002/acn3.51362

Objective Mutations in the HSPB1 gene are associated with a distal hereditary motor neuropathy type 2 (dHMN2) or Charcot‐Marie‐Tooth disease type 2F (CMT2F), usually with autosomal dominant inheritance. This study aimed to describe the phenotype of the HSPB1 c.407G>T (p.Arg136Leu) mutation at early and late stages of the disease course. Methods We identified this mutation (previously reported in patients from Italy) in a heterozygous state, among 14 individuals from eight families of Jewish Iranian descent. The clinical, electrophysiological and ultrasonographic features were evaluated during early (less than 5 years, N = 9) or late disease course (N = 5). Results The majority of subjects were males with a mean age at onset of 43.4 years (range 21‐67). Common initial symptoms were gait imbalance, distal (often asymmetric) lower limb weakness and feet numbness. Neurological examination in early disease course showed distal lower extremity weakness in nearly all cases, and absent Achilles tendon reflex in about half. A minority had distal loss of pain, vibration or position sensation. These findings were more prevalent in late disease stage. Electrodiagnostic studies demonstrated a length‐dependent axonal motor neuropathy, with typical preferential involvement of the tibial nerve. Muscle ultrasound showed a corresponding length‐dependent increase of homogeneous echo‐intensity, most noticeably in the gastrocnemius. One patient had a dual diagnosis of CMT2F and CMT2W. Interpretation The HSPB1 c.407G>G (p.Arg136Leu) mutation causes an adult‐onset, predominantly motor, axonal neuropathy in individuals of Jewish Iranian descent. Variable manifestations are noticed, and sensory involvement is more prominent in prolonged disease duration.