Frédérique Depierreux

Introduction: Heterozygous pathogenic variants in MYH3 are known to be responsible for distal arthrogryposis. Case report: We report a consanguineous family of four children with two likely pathogenic MYH3 homozygous variants associated with complex movement disorders, especially prominent lingual dystonia, along with skeletal abnormalities. The two variants in MYH3 (c.3445G>A and c.4760T>C) have already been described in patients with congenital arthrogryposis. No other significant variation was found using long-read whole genome sequencing. Discussion: We have extended the phenotype of MYH3-associated arthrogryposis to include movement disorders, which may have been underdiagnosed to date. Highlights This article extends the phenotype of MYH3-associated arthrogryposis to include movement disorders, illustrating a family of four children presenting MYH3 skeletal disorders and lingual dystonia. Two homozygous likely pathogenic variants have been identified in the four sibs and appear to be causative for both skeletal and neurological phenotypes.

ATP1A2 and CACNA1A genes encode proteins forming transmembrane channels, Na+/K+/ATPase transporter, and voltage-gated calcium channels, respectively. Pathogenic variants in these genes are associated with hemiplegic migraines, movement disorders, and developmental and epileptic encephalopathy.We report a child presenting epileptic encephalopathy with cognitive and behavioral troubles. He carries a likely pathogenic variant in the ATP1A2 gene, inherited from his mother who presents hemiplegic migraines, and a variant of uncertain significance in the CACNA1A gene, inherited from his asymptomatic father and also found in his brother, who presents a milder neurodevelopmental disorder (NDD). No other significant copy number or single nucleotide variations were identified after an in-depth genetic study including whole exome sequencing, array comparative genomic hybridization, and screening for Fragile X and Prader–Willi/Angelman syndromes.We illustrate the synergetic impact of ATP1A2 and CACNA1A genes in NDDs.

While levodopa may benefit some patients with monogenic Parkinson’s Disease and parkinsonism, others may exhibit aberrant responses earlier after exposure. Reporting treatment responses in rare genetic parkinsonism will help tailor therapeutic approaches to specific patients subpopulations. We report the therapeutic response in a patient with RAB39B X-linked parkinsonism, who exhibited motor and non-motor complications within a few months of Levodopa. Severe and debilitating Levodopa-induced complications can occur very early in the treatment course of X-linked parkinsonism, highlighting the need for an individualized therapeutic approach and follow-up in rare parkinsonian syndromes.

Hemifacial spasm (HFS) is characterised by intermittent, brief or sustained, repetitive contractions of the muscles innervated by one facial nerve. It is one of the most frequent movement disorders affecting the face. However common and allegedly straightforward to diagnose, it might reveal as a challenge for clinicians in various situations. Indeed, it often needs prior exclusion of many other movement disorders affecting the face, with frequent phenomenological overlaps with blepharospasm, post-facial palsy, facial motor tics, etc. The clinical diagnosis shall be supported by modern brain imaging techniques, and sometimes electromyography, as some particular aetiologies may require specific treatment. Primary forms are associated with vascular compression of the ipsilateral seventh cranial nerve, whereas secondary forms can be caused by any injury occurring on the facial nerve course. This article proposes a global and organised approach to the diagnosis, and the ensuing therapeutic options, as many practitioners still use some inefficient medications when they encounter a case of facial spasm.

We report the case of a 7-year-old boy affected by AIFM1 variant[1] [2] who progressively developed severe ataxia at 5 years of age. A brain magnetic resonance imaging (MRI) showed vermian atrophy and electromyography revealed four limbs polyneuropathy. Genetic analysis showed a maternally inherited variant in AIFM1 gene (c.470C > T[p.Ala157Val]). At 7 years of age, he presented with atypical hemifacial spasm developed over a few days. In addition to cerebellar ataxia and dysarthria, clinical examination identified severe and disabling right hemifacial spasm ([Video 1]; available in the online version), characterized by irregular and unusually fast clonic movements of the facial muscles,[3] combined with mild right facial paresis, and with left laterocolis and right torticolis, indicating an implication of the 11th cranial nerve. Electroencephalogram (EEG) was normal and brain MRI remained unchanged. Video 1 Part 1: cranial nerve examination showing severe, irregular and fast clonic movements of the right part of the face, right torticolis and left laterocolis. Speech (in French) was also impaired, suggesting larynx involvement. Part 2: upper limbs examination revealing fast myoclonus of the right upper limb in various situations (posture, rest, etc.). Part 3: gait examination, showing cerebellar ataxia. Over the following months, myoclonus appeared in his right upper limb, whereas hemifacial spasm spontaneously disappeared, as did myoclonus later. Myoclonus has only been described once in a patient with AFM1 variant, affecting the upper limb, then spreading to the other limbs, as well as the nostrils and larynx.[2] The authors suggested brainstem originated myoclonus in that case. Hemifacial spasm, considered as a peripheral myoclonus, is in the same clinical spectrum, and we suspect a similar origin in our patient. Received: 02 December 2021 Accepted: 31 January 2022 Publication Date: 09 March 2022 (online) © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Mutations in RAB39B gene have been linked to intellectual deficiency associated with parkinsonism, also referred as to Waisman syndrome. As it appears to be a very rare cause of Parkinson Disease (PD), with only few cases described in the literature, the typical clinical and radiological features are yet to be determined. In this article, we report and illustrate multimodal brain imaging by computed tomography, magnetic resonance imaging, transcranial ultrasound (US), dopamine transporter single photon emission computed tomography and [¹⁸F]-fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG-PET) in a 37-year-old man with PD features and mild mental retardation harboring a new RAB39B mutation. We then propose a comparison with data previously published regarding neuroimaging in this condition and present a summary of previous imaging reports. If our patient’s results partly support previously described radiological features, they also highlight potential new characteristics of this rare syndrome. To the best of our knowledge, [¹⁸F]FDG-PET and transcranial US have never been reported before in this condition. This is therefore the first multimodal brain imaging description of a patient presenting RAB39B mutation.

Parkinson’s disease (PD) is a neurodegenerative synucleinopathy characterized by the degeneration of neuromelanin (NM)-containing dopaminergic neurons and deposition of iron in the substantia nigra (SN). How regional NM loss and iron accumulation within specific areas of SN relate to nigro-striatal dysfunction needs to be clarified. We measured dopaminergic function in pre- and postcommissural putamen by [¹⁸F]DOPA PET in 23 Parkinson’s disease patients and 23 healthy control (HC) participants in whom NM content and iron load were assessed in medial and lateral SN, respectively, by NM-sensitive and quantitative R2* MRI. Data analysis consisted of voxelwise regressions testing the group effect and its interaction with NM or iron signals. In PD patients, R2* was selectively increased in left lateral SN as compared to healthy participants, suggesting a local accumulation of iron in Parkinson’s disease. By contrast, NM signal differed between PD and HC, without specific regional specificity within SN. Dopaminergic function in posterior putamen decreased as R2* increased in lateral SN, indicating that dopaminergic function impairment progresses with iron accumulation in the SN. Dopaminergic function was also positively correlated with NM signal in lateral SN, indicating that dopaminergic function impairment progresses with depigmentation in the SN. A complex relationship was detected between R2* in the lateral SN and NM signal in the medial SN. In conclusion, multimodal imaging reveals regionally specific relationships between iron accumulation and depigmentation within the SN of Parkinson’s disease and provides in vivo insights in its neuropathology.

Cervical dystonia is one of the most frequent form of focal dystonia. However, there's a great lack of awareness of this condition : a long delay to diagnosis is quite common and misdiagnosis is often seen. Nevertheless, this pathology is invalidating and improving diagnosis could have an impact on the treatment and the patient's quality of life.

Cosmetic or therapeutic use of botulinum toxin type A (BoNT-A) is usually safe but can rarely cause iatrogenic botulism. Iatrogenic botulism and myasthenia gravis (MG) share similar clinical features, because both BoNT-A and anti-acetylcholine receptorantibodies impair neuromuscular transmission. We report a patient who underwent cosmetic BoNT-A injection and later developed serious local and systemic adverse reactions. The peculiarity of this case is that a latent seropositive MG was eventually discovered, suggesting that both iatrogenic botulism and MG contributed to the clinical picture. This patient is one of the less than 10 reported cases worldwide in whom MG was unmasked by BoNT-A injection. He is the first to be assessed in detail by single-fiber electromyography. This case emphasizes the risk associated with BoNT-A injection in patients with subclinical impairment of neuromuscular transmission and prompts the search for MG in case of exaggerated response.