KCNQ2 encephalopathy: A case due to a de novo deletion Spagnoli, Carlotta; Salerno, Grazia Gabriella; Iodice, Alessandro ...
Brain & development (Tokyo. 1979),
January 2018, 2018-Jan, 2018-01-00, 20180101, Letnik:
40, Številka:
1
Journal Article
Recenzirano
KCNQ2 encephalopathy is characterized by severely abnormal EEG, neonatal-onset epilepsy and developmental delay. It is caused by mutations (typically missense) in the KCNQ2 gene, encoding the voltage ...gated potassium channel Kv7.2 and leading to a negative-dominant effect. We present one case experiencing recurrent neonatal seizures with changing hemispheres of origin, reminiscent of epilepsy of infancy with migrating focal seizures. At 9months of age the patient is still seizure-free on carbamazepine, although he is developing a spastic-dystonic tetraplegia with severe dysphagia. He harbors a de novo deletion (c.913_915del p.Phe305del)), only described once in a couple of severely affected twins, and leading to the deletion of a phenylalanine residue in the pore domain of the channel. In conclusion, our case is the second described with encephalopathy due to this specific deletion (the one and only deletion so far reported in KCNQ2 encephalopathy). Thus, deletion is a newly described mechanism highlighting how not only missense mutations but also deletions in the channel hot spots can lead to a severe phenotype. Furthermore he presented ictal EEG features similar to epilepsy of infancy with migrating focal seizures not previously described.
Abstract
Background
Tolosa-Hunt syndrome (THS) and recurrent painful ophthalmoplegic neuropathy (RPON) are rare diseases reported within the “Painful lesions of the cranial nerves” section of the ...International Classification of Headache Disorders-3
rd
edition (ICHD-3). In case of a first painful attack, differential diagnosis could be challenging and many pitfalls are due to the rarity of the disorders and the lack of information about correct medical management in youngsters.
Case presentation
Our main purpose was to report a new case of THS and a new case of RPON describing management and diagnostic investigation at the time of the first episode.
In both cases of THS (13 years old) and RPON (14 years old) a unilateral periorbital headache associated with acute onset of ipsilateral third cranial nerve paresis, scarcely responding to non-steroidal anti-inflammatory drugs (NSAID), was present at the beginning of the first attack. Brain MRI with "time-of-flight" (TOF) angiography and the need to administer steroids (after 72 h from onset) in order to stop pain were the most important handles allowing us to adopt the correct management both in THS or RPON since onset and to face recurrences in RPON by avoiding useless therapy during follow-up.
Conclusion
Unilateral periorbital headache associated with third-fourth or sixth cranial nerve paresis should ideally be investigated with a full work-up, comprehensive of brain MRI with TOF angiography since the first attack. In cases with negative brain MRI spontaneous resolution should be considered and watchful waiting might be advisable before starting steroid therapy.
Abstract Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder characterized by infantile onset of rapid motor and cognitive regression and hypotonia evolving into spasticity. ...Recessively inherited mutations of the PLA2G6 gene are causative of infantile neuroaxonal dystrophy and other PLA2G6 -associated neurodegeneration, which includes conditions known as atypical neuroaxonal dystrophy, Karak syndrome and early-onset dystonia-parkinsonism with cognitive impairment. Phenotypic spectrum continues to evolve and genotype-phenotype correlations are currently limited. Due to the overlapping phenotypes and heterogeneity of clinical findings characterization of the syndrome is not always achievable. We reviewed the most recent clinical and neuroradiological information in the way to make easier differential diagnosis with other degenerative disorders in the paediatric age. Recognizing subtle signs and symptoms is a fascinating challenge to drive towards better diagnostic and genetic investigations.
Abstract
Background
Mowat–Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the
ZEB2
gene. It is characterized by moderate-severe ...intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children.
Results
In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build.
Conclusions
These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS.
Moyamoya is a rare progressive cerebral arteriopathy, occurring as an isolated phenomenon (moyamoya disease, MMD) or associated with other conditions (moyamoya syndrome, MMS), responsible for 6-10% ...of all childhood strokes and transient ischemic attacks (TIAs).
We conducted a retrospective multicenter study on pediatric-onset MMD/MMS in Italy in order to characterize disease presentation, course, management, neuroradiology, and outcome in a European country.
A total of 65 patients (34/65 women) with MMD (27/65) or MMS (38/65) were included. About 18% (12/65) of patients were asymptomatic and diagnosed incidentally during investigations performed for an underlying condition (incMMS), whereas 82% (53/65) of patients with MMD or MMS were diagnosed due to the presence of neurological symptoms (symptMMD/MMS). Of these latter, before diagnosis, 66% (43/65) of patients suffered from cerebrovascular events with or without other manifestations (ischemic stroke 42%, 27/65; TIA 32%, 21/65; and no hemorrhagic strokes), 18% (12/65) of them reported headache (in 4/12 headache was not associated with any other manifestation), and 26% (17/65) of them experienced multiple phenotypes (≥2 among: stroke/TIA/seizures/headache/others). Neuroradiology disclosed ≥1 ischemic lesion in 67% (39/58) of patients and posterior circulation involvement in 51% (30/58) of them. About 73% (47/64) of patients underwent surgery, and 69% (45/65) of them received aspirin, but after diagnosis, further stroke events occurred in 20% (12/61) of them, including operated patients (11%, 5/47). Between symptom onset and last follow-up, the overall patient/year incidence of stroke was 10.26% (IC 95% 7.58-13.88%). At last follow-up (median 4 years after diagnosis, range 0.5-15), 43% (26/61) of patients had motor deficits, 31% (19/61) of them had intellectual disability, 13% (8/61) of them had epilepsy, 11% (7/61) of them had behavioral problems, and 25% (13/52) of them had mRS > 2. The proportion of final mRS > 2 was significantly higher in patients with symptMMD/MMS than in patients with incMMS (
= 0.021). Onset age <4 years and stroke before diagnosis were significantly associated with increased risk of intellectual disability (
= 0.0010 and
= 0.0071, respectively) and mRS > 2 at follow-up (
= 0.0106 and
= 0.0009, respectively).
Moyamoya is a severe condition that may affect young children and frequently cause cerebrovascular events throughout the disease course, but may also manifest with multiple and non-cerebrovascular clinical phenotypes including headache (isolated or associated with other manifestations), seizures, and movement disorder. Younger onset age and stroke before diagnosis may associate with increased risk of worse outcome (final mRS > 2).
Status dystonicus (SD) is a movement disorder emergency associated with significant morbidity and life-threatening events that requires immediate and effective treatment. Nevertheless, SD is ...currently an under-recognized and undertreated condition, partly due to the lack of a standard definition and because it can be the acute complicated course of both primary and secondary dystonias. In subjects with SD, due to the delay of identification and lacking prevention of trigger and precipitant factors, intensive care management is consistently required.
We performed a critical review of this topic, outlining clinical features and linked genetic disorders to recognize subject at higher risk of SD, describing precipitant and trigger factors and proposing potential pharmacological treatment strategies in order to prevent hospitalization.
Genetic predisposition included: primary dystonias particularly in the case of TOR1A mutation; epileptic encephalopathy such as ARX and GNAO1 genetic variants and neurodegenerative disorders as PANK2. Early recognition of SD should be oriented by the following sign and symptoms: fever, tachycardia, respiratory change, hypertension, sweating and autonomic instability, elevated serum CK. Pain, fever and dehydration are main trigger factors that have to be prevented or quickly controlled. Achieving sleep could be the first therapeutic option in those with high risk of developing SD. Recently, enteral or transdermal clonidine as safety and efficacy therapeutic alternative was proposed.
Recognizing high risk children for Status dystonicus from the onset of subtle signs and avoiding trigger factors could drive towards better management avoiding intensive treatments.
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