Megalencephalic leukoencephalopathy with subcortical cysts

Abstract

ObjectiveTo provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features.MethodsWe performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review.ResultsWe included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B.ConclusionClinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype.

An Asymptomatic Case of Megalencephalic Leukoencephalopathy with Subcortical Cysts

“…This mutation showed apparently reduced penetrance or more strongly variable expressivity in this family from a classic presentation of MLC in a child (index case) to an asymptomatic adult individual (index case's mother). Altogether, previous data shows this mutation has a high penetrance; clinical variability within this family might be attributed to genetic modifiers (17). There are some probabilities about the subclinical phenotype of the individuals carrying this mutation.…”

“…Macrocephaly, lower limbs spasticity, cognitive impairment and behavioral abnormalities without seizure were the main clinical features of the proband case, in addition to white matter involvements but detailed neurological examination on probond's mother revealed she was normal except for increased deep tendon reflexes in lower limbs at both knee and ankle joints (3/4). Her head circumference was 57 cm that seems to be in borderline range of macrocephaly for women (17). Nevertheless, diffuse white matter involvements and anterior temporal subcortical cysts were found in mother; she was also homozygous for the pathogenic variant of the proband case.…”

Practical Approaches and Knowledge Gaps in the Care for Children With Leukodystrophies

“…Targeted treatment of underlying pain causes Therapeutic massage, application of heat or cold, Reiki 61 Physical/occupational therapies 61 Rocking, repositioning, music, lighting, warm water, vibration NSAIDs and acetaminophen 46 NSAIDs and acetaminophen 46 Gabapentin 62 Consideration of opioids 46 Spasticity management (eg, benzodiazepines, antispasmodics) 6 leukoencephalopathy with subcortical cysts reported autistic features and cognitive decline. 87 Providers should support therapists and educators in anticipating increasing needs as the disease progresses. An individualized educational plan (IEP) with educational accommodations and therapies can help maximize developmental progress and quality of life.…”

Genetics and genomics in Peru: Clinical and research perspective

“…These microduplications correlated to Laurin–Sandrow syndrome and Haas‐type polysyndactyly, according to the ZRS region length (Lohan et al, ). Moreover, Peruvian geneticists of INSN described unique cases of pterygium‐digital keloid dysplasia (Abarca et al, ), H syndrome (Abarca Barriga, Trubnykova, Polar Córdoba, Ramos Diaz, & Aviles, ), van der Knaap syndrome (Hamilton et al, ), and Shawaf‐Traboulsi syndrome (Abarca Barriga et al, ). Last, international collaboration permitted reports of two common genetic syndromes—that is, Noonan (Kruszka et al, ) and Williams‐Beuren (Kruszka et al, )—with clinical geneticists of the National Human Genome Research Institute of The National Institutes of Health; and with other geneticists of different sites in the globe, contributing to the worldwide clinical genetics area.…”