Objective To test the hypothesis that predisposition to childhood herpes simplex virus (HSV) type 1 encephalitis (HSE) may be determined in part by human genetic factors. Study design A genetic ...epidemiologic survey of childhood HSE (onset at age 3 months to 15 years) over a 20-year period (1985-2004) was conducted throughout France (comprising 29 university hospital neuropediatric centers). A total of 85 children fulfilled the diagnostic criteria for inclusion. Family and personal histories were obtained by face-to-face interview for 51 patients. Results No familial cases of HSE were identified in our survey; however, a high proportion (20%) of the children interviewed had a relevant family history: parental consanguinity (12% of patients), early-onset herpetic keratitis in a first-degree relative (6%), or both (2%). The narrow window of high susceptibility to HSE before age 3 years (62% of patients) further indicates that predisposition to HSE is tightly age-dependent. Conclusions This survey suggests that childhood HSE, although sporadic, may result from Mendelian predisposition (from autosomal recessive susceptibility in particular), at least in some children. There likely is incomplete penetrance, however, which may reflect, at least in part, the impact of age at the time of HSV-1 infection.
Paediatric patients are at high risk of medication errors and adverse drug events due to complex medical care.
To assess the impact of pharmacist medication review for paediatric patients.
A ...single-centre prospective observational study was performed over 33 months, from February 2018 to October 2020 in a French Hospital.
Clinical pharmacists provided medication counselling at a hospital and conducted telephone follow-ups between 3 and 7 days after discharge of paediatric patients with chronic diseases for whom treatment was introduced or modified during hospitalisation or hospital consultations.
The incidence of drug-related problems (DRPs), the number and type of pharmacist intervention and paediatrician acceptance rates were assessed. Parents' understanding and drug-related needs were compared before and after medication review. Time to outpatient treatment and patient satisfaction were determined. Statistical analyses were performed in Excel.
In total, 195 paediatric patients were included. Pharmacists identified 65 interventions, 95% of which were accepted. The most frequent DRPs included inappropriate drug administration (32.3%), herb-drug interactions (24.6%) and dose selection (17%). Parents' knowledge increased by 28% from baseline after pharmacist's medication counselling. Parents' drug-related needs concerning administration and side effects decreased by 67% and 49%, respectively, following the pharmacist's medication counselling. Most (75%) of the patients were able to get their treatment immediately after discharge.
Clinical pharmacists can improve medication safety for children during the discharge process or consultations, by reducing prescription errors, optimising administration, counselling patients or parents and helping to ensure care continuity.
Xq28 int22h-1/int22h-2 duplication is the result of non-allelic homologous recombination between int22h-1/int22h-2 repeats separated by 0.5 Mb. It is responsible for a syndromic form of intellectual ...disability (ID), with recurrent infections and atopic diseases. Minor defects, nonspecific facial dysmorphic features, and overweight have also been described. Half of female carriers have been reported with ID, whereas all reported evaluated born males present mild to moderate ID, suggesting complete penetrance. We collected data on 15 families from eight university hospitals. Among them, 40 patients, 21 females (one fetus), and 19 males (two fetuses), were carriers of typical or atypical Xq28 int22h-1/int22h-2 duplication. Twenty-one individuals were considered asymptomatic (16 females and 5 males), without significantly higher rate of recurrent infections, atopia, overweight, or facial dysmorphism. Approximately 67% live-born males and 23% live-born female carriers of the typical duplication did not have obvious signs of intellectual disability, suggesting previously undescribed incomplete penetrance or low expression in certain carriers. The possibility of a second-hit or modifying factors to this possible susceptibility locus is yet to be studied but a possible observational bias should be considered in assessing such challenging X-chromosome copy number gains. Additional segregation studies should help to quantify this newly described incomplete penetrance.
The Forkhead box G1 (FOXG1) gene has been implicated in severe Rett-like phenotypes. It encodes the Forkhead box protein G1, a winged-helix transcriptional repressor critical for forebrain ...development. Recently, the core FOXG1 syndrome was defined as postnatal microcephaly, severe mental retardation, absent language, dyskinesia, and dysgenesis of the corpus callosum. We present seven additional patients with a severe Rett-like neurodevelopment disorder associated with de novo FOXG1 point mutations (two cases) or 14q12 deletions (five cases). We expand the mutational spectrum in patients with FOXG1-related encephalopathies and precise the core FOXG1 syndrome phenotype. Dysgenesis of the corpus callosum and dyskinesia are not always present in FOXG1-mutated patients. We believe that the FOXG1 gene should be considered in severely mentally retarded patients (no speech-language) with severe acquired microcephaly (-4 to-6 SD) and few clinical features suggestive of Rett syndrome. Interestingly enough, three 14q12 deletions that do not include the FOXG1 gene are associated with phenotypes very reminiscent to that of FOXG1-mutation-positive patients. We physically mapped a putative long-range FOXG1-regulatory element in a 0.43 Mb DNA segment encompassing the PRKD1 locus. In fibroblast cells, a cis-acting regulatory sequence located more than 0.6 Mb away from FOXG1 acts as a silencer at the transcriptional level. These data are important for clinicians and for molecular biologists involved in the management of patients with severe encephalopathies compatible with a FOXG1-related phenotype.
Background and aim
To improve the diagnostic work-up of patients with diverse neurological diseases, we have elaborated specific clinical and CSF neurotransmitter patterns.
Methods
Neurotransmitter ...determinations in CSF from 1200 patients revealed abnormal values in 228 (19%) cases. In 54/228 (24%) patients, a final diagnosis was identified.
Results
We have reported primary (30/54, 56%) and secondary (24/54, 44%) monoamine neurotransmitter disorders. For primary deficiencies, the most frequently mutated gene was
DDC
(
n
= 9), and the others included
PAH
with neuropsychiatric features (
n
= 4),
PTS
(
n
= 5),
QDPR
(
n
= 3),
SR
(
n
= 1), and
TH
(
n
= 1). We have also identified mutations in
SLC6A3
,
FOXG1
(
n
= 1 of each),
MTHFR
(
n
= 3),
FOLR1
, and
MTHFD
(
n
= 1 of each), for dopamine transporter, neuronal development, and folate metabolism disorders, respectively. For secondary deficiencies, we have identified
POLG
(
n
= 3),
ACSF3
(
n
= 1),
NFU1
, and
SDHD
(
n
= 1 of each), playing a role in mitochondrial function. Other mutated genes included:
ADAR
,
RNASEH2B
,
RNASET2
,
SLC7A2-IT1 A/B lncRNA
, and
EXOSC3
involved in nuclear and cytoplasmic metabolism;
RanBP2
and
CASK
implicated in post-traductional and scaffolding modifications
; SLC6A19
regulating amino acid transport;
MTM1
,
KCNQ2
(
n
= 2), and
ATP1A3
playing a role in nerve cell electrophysiological state. Chromosome abnormalities,
del(8)(p23)/dup(12) (p23)
(
n
= 1),
del(6)(q21)
(
n
= 1),
dup(17)(p13.3)
(
n
= 1), and non-genetic etiologies (
n
= 3) were also identified.
Conclusion
We have classified the final 54 diagnoses in 11 distinctive biochemical profiles and described them through 20 clinical features. To identify the specific molecular cause of abnormal NT profiles, (targeted) genomics might be used, to improve diagnosis and allow early treatment of complex and rare neurological genetic diseases.
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