Management strategies for CLN2 disease Williams, Ruth E., DM, FRCPCH; Adams, Heather R., PhD; Blohm, Martin, MD ...
Pediatric neurology,
04/2017, Letnik:
69
Journal Article
Recenzirano
Odprti dostop
Abstract CLN2 disease (neuronal ceroid lipofuscinosis type 2) is a rare, autosomal recessive, pediatric-onset, rapidly progressive neurodegenerative lysosomal storage disorder caused by TPP1 enzyme ...deficiency, and is characterized by language delay, seizures, rapid cognitive and motor decline, blindness and early death. No management guidelines exist and there is a paucity of published disease-specific evidence to inform clinical practice, which currently draws upon experience from the field of childhood neurodisability. Twenty-four disease experts were surveyed on CLN2 disease management and a subset met to discuss current practice. Management goals and strategies are consistent among experts globally, and are guided by the principles of pediatric palliative care. Goals and interventions evolve as the disease progresses, with a shift in focus from maintenance of function early in the disease to maintenance of quality of life. A multidisciplinary approach is critical for optimal patient care. This work represents an initial step towards development of consensus-based management guidelines for CLN2 disease.
Abstract Background Dup(14q12) harboring FOXG1 has been recently reported in individuals with developmental delay of variable severity, delayed/absent speech, and epilepsy/infantile spasms. FOXG1 was ...described as a dosage-sensitive gene encoding G1, a forkhead protein that is a brain-specific transcription factor with a role in brain development. Patients We extensively reviewed all published cases with dup(14) harboring FOXG1 and highlighted those epileptological features that are more commonly found among such cases. We also describe one new patient, detailing his peculiar clinical and neurophysiological findings. Results To date, 15 patients with dup(14) including FOXG1 have been reported; within those patients, nine also presented with epilepsy. At onset, the more frequent seizure type in the report and also in our patient is the epileptic spasm. Focal seizures might also be present. Outcomes in patients with epilepsy associated with dup(14) should be considered separately regarding seizures and cognitive and motor development. In the majority of patients (seven of 10, including ours), seizures tend to disappear and motor skills improve; however, instead stagnation of cognitive development is evident in all of them, associated with severe speech difficulties. Conclusions There are some common features that should be considered: seizures with onset during the first year of life, particularly clusters of spasms and focal seizures with hypsarrhythmic electroencephalograph pattern; different degrees of cognitive impairment possibly associated with behavior disturbances and severe speech disabilities; and dysmorphic features in the absence of significant microcephaly.
Abstract Mutations in the CACNA1A gene, encoding the pore-forming CaV2.1 (P/Q-type) channel α1A subunit, localized at presynaptic terminals of brain and cerebellar neurons, result in clinically ...variable neurological disorders including hemiplegic migraine (HM) and episodic or progressive adult-onset ataxia (EA2, SCA6). Most recently, CACNA1A mutations have been identified in patients with nonprogressive congenital ataxia (NPCA). We performed targeted resequencing of known genes involved in cerebellar dysfunction, in 48 patients with congenital or early onset ataxia associated with cerebellar and/or vermis atrophy. De novo missense mutations of CACNA1A were found in four patients (4/48, ∼8.3%). Three of them developed migraine before or after the onset of ataxia. Seizures were present in half of the cases. Our results expand the clinical and mutational spectrum of CACNA1A -related phenotype in childhood and suggest that CACNA1A screening should be implemented in this subgroup of ataxias.
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