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Convergent pathological and ultrasound features in hereditary syndromic and non‐syndromic minifascicular neuropathy related to DHH
Author(s) -
Boso Federica,
Zanette Giampietro,
Baldinotti Fulvia,
Bertelloni Silvano,
Taioli Federica,
Monaco Salvatore,
Fabrizi Gian Maria,
Cavallaro Tiziana
Publication year - 2020
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/jns.12417
Subject(s) - medicine , proband , pathological , sural nerve , nerve biopsy , hereditary motor and sensory neuropathy , pathology , peripheral neuropathy , short stature , anatomy , mutation , disease , biology , endocrinology , genetics , gene , diabetes mellitus
Minifascicular neuropathy (MN) is a rare, autosomal recessive disease with prominent structural changes of peripheral nerves. So far, it has been observed in females with a 46,XY karyotype and mutations of the Desert Hedgehog ( DHH ) gene, thus linking MN to gonadal dysgenesis (GD) and disorders of sex development (DSD). However, a 46,XX proband with normal female sex and gender development underwent clinical evaluations, nerve conduction studies and genetic screening for a severe motor‐sensory neuropathy with a pathological phenotype that hinted at MN. Indeed, sural nerve biopsy revealed a profound disturbance of perineurium development with a thin and loose structure. High‐resolution ultrasound (HRUS) also disclosed diffuse changes of nerve echotexture that visibly correlated with the pathological features. After extensive genetic testing, a novel homozygous DHH null mutation (p.Ser185*) was identified in the proband and in her sister, who was affected by a similar motor‐sensory neuropathy, but was eventually found to be a 46,XY patient according to a late diagnosis of DSD with complete GD. DHH should therefore be considered as a possible cause of rare non‐syndromic hereditary motor‐sensory neuropathies, regardless of DSD. Furthermore, HRUS could effectively smooth the complex diagnostic workup as it demonstrated a high predictive power to detect MN, providing the same detailed correlations to the pathologic features of the nerve biopsy and Dhh −/− mice in both sisters. Hence, HRUS may assume a pivotal role in guiding molecular analysis in individuals with or without DSD.