Kearns-Sayre syndrome with facial and white matter extensive involvement: a (mitochondrial and nuclear gene related?) neurocristopathy?

The Authors report on a patient with Kearns-Sayre syndrome, large mtDNA deletion (7/kb), facial abnormalities and severe central nervous system (CNS) white matter radiological features, commonly attributed to spongy alterations. The common origin from neural crest cell (NCC) of facial structures (cartilagineous, osseous, vascular and of the peripheral nervous system) and of peripheral glia and partially of the CNS white matter are underlined and the facial and glial abnormalities are attributed to the abnormal reproduction/migration of NCC. In this view, the CNS spongy alterations in KSS may be not only a dystrophic process (leukodystrophy) but also a dysplastic condition (leukodysplasia). The Authors hypothesize that the symptoms may be related to mtDNA mutations associated to NCC nuclear gene abnormality. SOX 10 gene may be a nuclear candidate gene, as reported in some case of Waardenburg IV syndrome.

Oculo-auriculo-vertebral spectrum with myopathy and velopharyngeal insufficiency. A case report with a non-branchiomeric muscle biopsy.

In the present paper we report on a case of oculo-auriculo-vertebral spectrum presenting fluorescence in situ hybridization and comparative genomic hybridization tests negative, hypotonia of some branchiomeric muscles (with velo-pharyngeal insufficiency, dysphagia and nasal voice) and non-branchiomeric muscles (with strabismus and limb hypotrophy). On the basis of the left quadriceps muscle biopsy, showing anisometry and prevalence of type 1 fibers, and on literature data, we underline the relevance of TBX1 gene (regulator of neural crest cells and activator of myogenic factors in branchiomeric muscles development) and of PAX3 gene (present in neural crest, inducing migration of these cells and reported in non-branchiomeric muscles). We conclude that the case of OAVS presented a generalized myopathy and we hypothesize that a cluster of genes strictly neural crest cells related, including TBX1 and PAX3, may be responsible of the branchiomeric and non-branchiomeric myopathy; alternatively, a regulatory mechanism abnormally common to OAVS and velo-cardio-facial syndrome could be present.

Oculo-auriculo-vertebral spectrum with craniosynostosis and osteo-cartilagineous multiple defects: a diffuse chondro-membranous-osteo-dysplasia.

We report on a female with oculo-auriculo-vertebral spectrum, low height, and on X-ray lambdoid suture synostosis, cerebral cyst/mild holoprosencephalia and cholesteatoma, and multiple abnormalities of bones of chondral origin. On the right side, maxillary, mandibular bones, external auditory canal, middle ear were hypoplastic as well as semicircular canal, cranial base, bones vestibule. On the left side, coclea, timpanic cavity, mastoid antrum were hypoplastic, while stapes was misshapen. Limbs bones were slender with thin metaphyses and some carpal bones were absent. Hand second phalanx was hypoplastic and fifth finger presented clynodactily. Lambdoid synostosis expressed membranous ossification abnormality. We hypothesize that during the blastogenesis a mutation of a factor responsible for abnormal generalized endochondral and connectival ossification (possibly fibroblast growth factor receptor) occurs.

Activity of drugs and components of natural origin in the severe myoclonic epilepsy of infancy (Dravet syndrome).

The sea anemones (Cnidaria) produce neurotoxins, polypeptides active on voltage-gated sodium channels, which induce a non-inactivating condition, with consequent seizures and paralysis in zebrafish (Danio rerio). In humans, severe myoclonic epilepsy of infancy (SMEI) is due to SCN1A gene mutation, which causes a non-inactivating sodium channels condition with seizures. Some symptoms, such as age of first seizure, repetitive events, frequent status epilepticus, scarce responsiveness to antiepileptic drugs (AEDs), may be due to superimposed environmental causes. The authors report a case of SMEI treated for years with benzodiazepines and subsequently with valproate. The attenuation of the frequency of epileptic events and of time in seizing, but no change in burst duration and EEG events was observed. These results are similar to those reported in the literature about zebrafish scn1Lab mutant, which recapitulates the SCN1A symptoms and AED resistance occurring in humans. During seizures the production of polypeptides similar to sea anemones neurotoxins, causing repetitive seizures, status epilepticus, and AED resistance can be hypothesized in subjects with SCN1A mutation.