Motor Neuropathy Type Research Articles

P14 Midface Toddler Excoriation Syndrome (MiTES): a new mimic of non-accidental injury

Abstract Background Midface Toddler Excoriation Syndrome (MiTES) is a rare genetic condition first described in 2017. Commencing in the first year of life, it is characterised by intense mid-­facial itch with persistent scratching and skin breakdown. Symptoms improve later in childhood, leaving atrophic scarring. Disbelief that infants can damage themselves in this way can lead to an erroneous and damaging misdiagnosis of non-accidental injury (NAI). Cases A boy now aged 11 years presented at 6 months with recurrent scratching of the face, leading to ulceration of the nasal bridge, sides of the nose, infraorbital areas and central forehead. Extensive investigations were unhelpful and NAI was suspected with significant psychosocial sequelae for the family. When his sister, now aged 4 years, presented with strikingly similar lesions MiTES was suspected and confirmed by genetic testing which showed homozygosity for 18 alanine repeats in the PRDM12 gene. Testing of sibling and parents is planned. Both children are now asymptomatic but have significant facial scarring. Discussion Biallelic variants in PRDM12 usually cause hereditary sensory and motor neuropathy type 8 with widespread damage to distal appendages due to pain insensitivity. The specific variant found here and in all reported MiTES cases causes highly localised lesions with rarely any extra-facial ­involvement. Due to its novelty and rarity, MiTES may be misdiagnosed and safeguarding concerns raised, leading to distress for affected families and breakdown of parent-­provider relationships. This case, which for the first time provides longitudinal data on affected siblings, highlights the need for early recognition and diagnosis.

Hereditary motor and sensory neuropathy type VIa with optic atrophy in two sisters with pathologic myopia: a case series and review

Hereditary motor and sensory neuropathy type VIa with optic atrophy in two sisters with pathologic myopia: a case series and review

A case of hereditary motor and sensory neuropathy type IVA with unusual genealogy

Background. Hereditary motor and sensory neuropathies (HMSN) are a genetically diverse group of disorders of the peripheral nerves characterized by gradual development of weakness, muscular hypo-/atrophy, sensory disturbances in distal areas of the extremities. Currently among the recessive forms, the most prevalent HMSN is associated with the ganglioside-induced differentiation associated-protein 1 (GDAP1) gene (GDAP1-HMSN).The objective is to present an observation of a family case of HMSN type IVA with unusual genealogy.Materials and methods. Clinical, electrophysiological, and genetic characteristics of a Russian family with GDAP1-HMSN were examined.Results. We describe a family with autosomal recessive HMSN and unusual genealogy due to homozygous and compound heterozygous mutations of GDAP1.Conclusion. The particularity of the described family case is the unusual genealogy with the patients in two non-consecutive generations. This type of inheritance is caused by presence of mutations in compound heterozygous state in the proband's grandson which was confirmed by genetic analysis. The presented case demonstrates the importance and necessity of full analysis of the GDAP1 gene or identification of 2 mutations in trans-position in the proband and subsequent assessment of possible risks for future generations. Multiple stroke-like episodes in the 2 affected members of the family are described that have not been previously reported for GDAP1-HMSN. Stroke has been presented in HMSN associated with mitofusin-2 gene which also as GDAP1, affects mitochondrial function in the neurons.

Mosaicism for GJB1 mutation causes milder Charcot-Marie-Tooth X1 phenotype in a heterozygous man than in a manifesting heterozygous woman

Charcot-Marie-Tooth (CMT) disease is a heterogeneous disorder of the peripheral nervous system that collectively affects approximately 1 in 2,500 individuals, thus making it the most common inherited neurologic disorder. X-linked inheritance may account for 10-20% of CMT neuropathy. We report a Czech family with a 30-year-old woman affected by CMT since the age of 10years, originally as an isolated case. Nerve conduction study (NCS) showed demyelinating neuropathy, and DNA testing revealed a novel heterozygous gap junction beta-1 protein (GJB1) mutation c.784_786delTA. The same mutation, but surprisingly in heterozygous state, was subsequently found in her subjectively healthy father and later also in one of her sisters but not in her two other sisters. NCS showed intermediate type of motor and sensory neuropathy in these two females manifesting heterozygotes and normal results in the other healthy sisters and one brother, all without the c.784_786delTA mutation. The father has a phenotype milder than his daughter and has only subclinical signs of CMT. The index female patient had normal karyotype 46, XX, and normal FISH for centromeric X chromosome. We concluded that the proband's father is a heterozygote due to the somatic mosaicism for the GJB1 mutation in his leukocytes (detected by DNA sequencing) and also in his germ cells as confirmed by the unexpectedly different genotypes in his four daughters. Quantitative analysis revealed a mutated signal in 25:75 allele proportion of mutated to healthy allele in the mosaic father. This study has important consequences for genetic counseling and prognosis in CMTX1 families.

19. Multimodal evoked potentials in hereditary motor and sensory neuropathy type 1

19. Multimodal evoked potentials in hereditary motor and sensory neuropathy type 1

Spectrum and frequency of mutations in the connexin 32 gene (GJB1) in hereditary and sensory neuropathy type 1X patients from Bashkortostan

Hereditary motor and sensory neuropathy type 1X (HMSN 1X) is the second most frequent form of demyelinating polyneuropathies and is caused by mutations in the gene for connexin 32 protein (Cx32, GJB1). The contribution of HMSN 1X to the structure of HMSN in the Republic of Bashkortostan was determined. The GJB1 mutations were detected in 18 out of 131 unrelated patients, which constituted 13.7%. The four missense mutations identified were represented by: Pro87Ala (c.259C>G) with the frequency of 10%; Arg22Gln (c.65G>A) (2.98%); Arg15Gln (c.44G>A); and Thr86Ile (c.257C<T) (0.8%). The latter mutation was never described before. The frequent mutation Pro87Ala was tested for linkage disequilibrium with the alleles of five polymorphic microsatellite DNA loci associated with the GJB1. It was demonstrated that 10 out of 13 chromosomes carrying the mutation mentioned had common DXS8111-DXS983-DXS8107-DXS8052 haplotype. This finding suggested the distribution of this mutation on the territory of the Republic of Bashkortostan as a result of the founder effect. The mutational spectrum of GJB1 and mutation frequencies observed in the HMSN 1X patients examined were characterized by ethnic heterogeneity. This finding will provide development of most optimal algorithm of the HMSN DNA diagnostics in the region.

The first Italian family with evidence of pyramidal impairment as phenotypic manifestation of Silver syndrome BSCL2 gene mutation

Silver syndrome (SPG17) is a rare form of hereditary spastic paraparesis. Its relationship to distal hereditary motor neuropathy (dHMN) type V is underlined by the recent discovery of causative mutation in BSCL2 gene coding for a protein termed seipin, an integral membrane protein of endoplasmic reticulum, with unknown function. Here we report the third Italian family with dHMN and SPG17 in which two affected members harbor the heterozygous N88S mutation in the BSCL2 gene. The proband developed a severe paraparetic spastic gait, while, in the other Italian families reported so far, no signs of upper motor neuron involvement were observed. This family confirms the clinical heterogeneity associated with this specific mutation. Moreover, this is the first report in which neuroimaging seems to confirm the pyramidal alterations in dHMN associated to SPG17.

P163 Electroneuromyography findings in patients with hereditary motor and sensory neuropathy type II

P163 Electroneuromyography findings in patients with hereditary motor and sensory neuropathy type II

Hereditary motor and sensory neuropathy type V or complicated form of spastic paraplegia?

Hereditary motor and sensory neuropathy type V or complicated form of spastic paraplegia?

Ambulatory disabilities and the use of walking aids in patients with Hereditary Motor and Sensory Neuropathy type I (HMSN I)

Purpose. To determine the level of ambulatory disability and the use of walking aids in well-ambulant Hereditary Motor and Sensory Neuropathy type I (HMSN I) patients, and to identify the related demographic, physical and psychological variables.Methods. Seventy-five well-ambulant HMSN I patients, aged 20 – 58 years, were measured in a cross-sectional assessment, addressing disability of ambulation and mobility (Sickness Impact Profile), demographics, muscle strength (Medical Research Council), use of walking aids, physical activity (actometer), fatigue (Checklist Individual Strength), and quality of life (EuroQoL).Results. Seventy-two percent of the patients perceived a significant amount of ambulatory disability. These patients were less active, and more fatigued compared to patients without ambulatory disability, and healthy reference groups. The total patient sample showed marked distal paresis (mean MRC=3.3), a high level of pain – discomfort (76%), but normal levels of employment (62.7%) and anxiety – depression (20%). Walking aids were used by 49% of the patients. These patients were older, less active, more fatigued, had less muscle strength, and perceived more disabilities of ambulation and mobility than non-users. Of the patients without walking aids, 41% perceived a significant amount of ambulatory disabilities.Conclusion. Ambulatory disability frequently occurred in well-ambulant HMSN I patients. The use of walking aids was not completely in accordance with the perceived ambulatory disability. Therefore prescription requires specific attention as well as complaints about pain and fatigue.

Early Clinical and Electrophysiologic Features of the Two Most Common Autosomal Recessive Forms of Charcot-Marie-Tooth Disease in the Roma (Gypsies)

Our recent studies of the genetic epidemiology of neuromuscular disorders in Gypsies in Bulgaria have revealed that two private disorders, hereditary motor and sensory neuropathy type Lom and hereditary motor and sensory neuropathy type Russe, account for most cases of Charcot-Marie-Tooth disease in this population. In this study, we examined the clinical and electrophysiologic manifestations of the two disorders in childhood, aiming to identify the distinctive features that allow early differential diagnosis. The study included 13 patients, aged between 2 and 15 years. The childhood clinical manifestations of both neuropathies were similar, although they tended to be more severe in hereditary motor and sensory neuropathy type Lom. The nerve conduction velocities in hereditary motor and sensory neuropathy type Lom were lower than in hereditary motor and sensory neuropathy type Russe. Brainstem auditory evoked potentials were abnormal in hereditary motor and sensory neuropathy type Lom, even at an early age, and normal in hereditary motor and sensory neuropathy type Russe. Although electrophysiologic data provide a more reliable differentiation than clinical data, the definitive diagnosis should rely on genetic testing. (J Child Neurol 2006;21:20-25).

A Family With Autosomal Dominant Mutilating Neuropathy Not Linked To Either Charcot-Marie-Tooth Disease Type 2B (CMT2B) or Hereditary Sensory Neuropathy Type I (HSN I) LOCI

Sensory loss and ulcero-mutilating features have been observed in hereditary sensory neuropathy type I and in her- editary motor and sensory neuropathy type IIB, also referred as Charcot-Marie-Tooth disease type 2B. To date two loci associated with ulcero-mutilating, neuropathy have been described: CMT2B at 3q13-q22 and HSN I at 9q22.1-q22.3. We performed linkage analysis with chromosomal markers representing the hereditary sensory neuropathy type I and Charcot-Marie-Tooth disease type 213 loci on an Italian family with a severe distal sensory loss leading to an ulcero-mutilating peripheral neuropathy. Negative likelihood-of-odds scores excluded any evidence of linkage to both chromosome 3q13 and chromosome 9q22 markers, confirming the genetic heterogeneity of this clinical entity and the presence of a third locus responsible for ulcero-mutilating neuropathies.

Hereditary motor and sensory neuropathy with absence of large myelinated fibers due to absence of large neurons in dorsal root ganglia and anterior horns, clinically associated with deafness, mental retardation, and epilepsy (HMSN‐ADM)

Hereditary motor and sensory neuropathy (HMSN) with autosomal recessive inheritance represents a genetically heterogeneous group of disorders with variable clinical, pathologic and electrophysiologic manifestations. A new variant of autosomal recessive HMSN, clinically defined by sensorimotor polyneuropathy associated with deafness and mental retardation, has recently been described. We report on the first autopsy case with this type of HMSN: a girl of non-consanguineous parents with a presumably autosomal recessive type of motor and sensory neuropathy clinically associated with deafness, mental retardation, and epilepsy. The autopsy showed complete absence of large myelinated fibers in peripheral motor and sensory nerves corresponding to a lack of large neurons in dorsal root ganglia and anterior horns of the spinal cord, moderate neurogenic muscle atrophy, and nearly complete absence of neurons in the dentate nucleus of the cerebellum. Molecular genetic analyses in our case revealed neither genetic alterations in the survival motor neuron gene nor in the PMP-22 gene.

Genetics of Motor and Sensory Neuropathy Type 2C

Thirty-three subjects in a large family with hereditary motor and sensory neuropathy (HMSN) type 2C were examined by linkage analysis at the Mayo Clinic, Rochester, MN.

Facial nerve dysfunction in hereditary motor and sensory neuropathy type I and III

Facial nerve dysfunction in hereditary motor and sensory neuropathy type I and III

Facial nerve dysfunction in hereditary motor and sensory neuropathy type I and III.

Facial nerve function was studied in 19 patients with hereditary motor and sensory neuropathy type I (HMSN I) and 2 patients with hereditary motor and sensory neuropathy type III (HMSN III, Déjérine-Sottas), and compared to that in 24 patients with Guillain-Barré syndrome (GBS). The facial nerve was stimulated electrically at the stylomastoid fossa, and magnetically in its proximal intracanalicular segment. Additionally, the face-associated motor cortex was stimulated magnetically. The facial nerve motor neurography was abnormal in 17 of 19 HMSN I patients and in both HMSN III patients, revealing moderate to marked conduction slowing in both the extracranial and intracranial nerve segments, along with variable reductions of compound muscle action potential (CMAP) amplitudes. The facial nerve conduction slowing paralleled that of limb nerves, but was not associated with clinical dysfunction of facial muscles, because none of the HMSN I patients had facial palsy. Conduction slowing was most severe in the HMSN III patients, but only slight facial weakness was present. In GBS, conduction slowing was less marked, but facial weakness exceeded that in HMSN patients in all cases. We conclude that involvement of the facial nerve is common in HMSN I and HMSN III. It affects the intra- and extracranial part of the facial nerve and is mostly subclinical.

CLINICAL, ELECTROPHYSIOLOGICAL, AND HISTOPATHOLOGIC STUDIES IN HEREDITARY MOTOR AND SENSORY NEUROPATHY V: ONE CASE REPORT

Hereditary motor and sensory neuropathy type V (HMSN V) is a rare disorder characterized by the clinical features of spastic paraplegia with peroneal muscular atrophy. A patient with progressive deformity of the feet due to HMSN V underwent clinical, electrophysiological, histopathological examinations, and surgical treatments. Physical examination revealed bilateral pes equinovarus and peroneal muscular atrophy with pyramidal tract features. In the lower limbs, motor nerve conduction velocity could not be determined, and sensory nerve conduction velocity was decreased. In contrast, the results of both the conduction studies were normal for the upper limbs. A sural nerve biopsy revealed a decrease in the number of myelinated fibers and in the diameter of the unmyelinated fibers, and axonal and myelin regeneration was found on light and electron microscopic examinations, suggesting an axonopathy. Since the patient had pyramidal tract features, the same pathological changes may be present in the spinal cord. In the surgical treatment to correct deformity of the feet in this patient, triple arthrodesis was necessary.

Developmental Hip Dysplasia in Hereditary Motor and Sensory Neuropathy Type 1

Severe hip dysplasia in children with hereditary motor and sensory neuropathy (HMSN) is not necessarily congenital. We describe three patients with late symptoms, two of them with proven normal hips until early adolescence. A careful follow-up of all children with HMSN for hip dysplasia should be carried out.

Expression of peripheral myelin protein-22 (PMP22)-mRNA in hereditary motor and sensory neuropathy type 1 (HMSN 1)

Expression of peripheral myelin protein-22 (PMP22)-mRNA in hereditary motor and sensory neuropathy type 1 (HMSN 1)

Clinical and morphological phenotype of HMSN 1A mosaicism

Clinical, neurophysiological and morphological studies on a patient with mosaicism of the 17p11.2 duplication were performed in detail for the first time. Since duplication occurs during paternal meiosis, a somatic reversion is suggested, leading to mosaicism. The proportion of nuclei with duplication varied markedly between 49% in blood cells and 74% in tissue from the sural nerve. Clinically, mild symptoms of a motor and sensory neuropathy were present. However, neurophysiological changes and findings in the sural nerve biopsy were consistent with a typical hereditary motor and sensory neuropathy type 1 (HMSN 1). Differing clinical findings in patients with mosaicism of the 17p11.2 duplication may be explained by a varying degree and/or time of reversion.