phenotypic description of patients with atypical clinical forms of pla2g6 mutations

Conditions: Neuroaxonal Dystrophy, Atypical

Summary: mutations in the pla2g6 gene are well known in the classical phenotype called infantile neuro-axonal dystrophy (inad), a severe neurodegenerative disease starting in infancy with homogeneous clinical, radiological, electrophysiological and pathophysiological features, with early death. other clinical forms in pediatric patients called atypic inad have been described in some patients. expansion of high-throughput sequencing in the last decades has lead to identify mutations in the pla2g6 gene in pediatric patients with late-onset phenotypes associating progressive ataxia, spastic paraplegia, cognitive regression and/or dystonia / parkinsonism. a high variability in radiological and electrophysiological findings is also described. less than twenty patients with a pediatric onset have been reported with an atypical inad. very poor data are available on management and therapeutic options in these patients and global prognostic is not known. this multicentric retrospective study will record clinical, radiological, electrophysiological and pathophysiological data in pediatric patients with genetically confirmed atypical inad. management, therapeutics and evolution of the disease will also be recorded.

patients with biallelic mutations in pla2g6 with an atypic inad starting before 18 years will be recruited after a collaboration call of neuropaediatricians in france. after family consent, a retrospective collection of data will be performed using redcap® digital questionnaire performed by the practitioner who follows / followed each patient. genetical, clinical, radiological, electrophysiological, pathophysiological outcomes will be anonymously recorded. therapeutics proposed to patients, potential complications of the disease or treatments, age of premature death will also be recorded. data will be computed numerically and analysed in the clermont-ferrand center. a descriptive analysis will be proposed as the expected number of patients affected by this rare disease varies from 10 to 30. median \[\]interquartiles\], means \[standard deviation\] and percentages will be calculated for quantitative data. collected data will include : * general information : * centre number * patient (first letter last name, first letter first name) * investigator name * patient age * patient sex * age at clinical onset * patient alive or deceased * age when deceased * ethnic origin * consanguinity * clinical data : * birth term * age at sitting * age at walking * age at first language * acquisition of fine motor skills * autistic troubles * motor regression and age * loss of walking and age * language regression and age * social skill regression and age * vision loss and age * hearing loss and age * progressivity of symptoms * axial hypotonia * ataxia * dystonia * parkinsonism * other paroxysmic movements * spasticity * hyperreflexia * hyporeflexia /areflexia * babinski sign * peripheral neuropathy * muscular atrophy * bulbar signs * dysarthria * nystagmus * strabism * seizures * intellectual deficiency and severity * specific learning disabilities * behavioral troubles * mood disorders * scoliosis * other orthopedic abnormalities * sleep disturbance or sleep apnea syndrome * gastro-intestinal troubles * other symptoms * patient still ambulant or not * gross motor function classification score (gmfcs from 1 to 5) * schooling modalities * eye fundus abnormalities * genetic data : - name of mutation 1 / mutation 2 in pla2g6 * radiological data : * iron deposits * white matter abnormalities * cerebellar atrophy * optic nerve atrophy * brainstem atrophy * cortical-subcortical atrophy * splenium verticalization * other abnormalities of corpus callosum * clava hypertrophy * other abnormalities * electrophysiological data : * abnormalities of eeg * abnormalities of electromyogram * other results of evoked potentials * pathophysiological data: * results of potential cutaneous, muscular, nervous or other biopsies * results of potential autopsy in case of deceased patients * therapeutical data : * type of feeding (oral, tube..) * ventilatory support * baclofen * botulinic toxin * l-dopa * trihexyphenidyl * tetrabenazine * antiepileptic drugs (names) * neuropathic analgesic * treatment os swallowing * mitochondrial cocktail or other vitamins * treatment of sleep disorders * orthopedic or other surgery * other symptomatic treatment * treatment leading to aggravation * treatment leading to improvement

Eligibility criteria:
inclusion criteria: * children with atypical neuroaxonal dystrophy under 18 years at disease-onset * with 2 deleterious mutations in the pla2g6 gene * alive or deceased * non-opposition of parents to participate to the retrospective study exclusion criteria: * classical form of infantile neuroaxonal dystrophy * neuro-axonal dystrophy with adult-onset * opposition of parents to participate to the retrospective study

Keywords: pla2g6 atypical infantile neuro-axonal dystrophy progressive ataxia karak syndrome pediatric parkinsonism cerebello-spastic syndrome