The aim of the study was to assess the validity of the use of the battery of tests assessing higher auditory functions in the diagnostic process of APD in 6-year-old children. The study involved ...1,012 Polish-speaking children aged 6 to 9 years with normal hearing sensitivity. The evaluation of auditory functions was performed using the ATS Neuroflow test battery comprising: Adaptive Speech in Noise test (ASPN-S), Dichotic Digits Test (DDT) and Frequency Pattern Test (FPT). Two groups were distinguished: the group”S” (Study) containing 880 participants with APD (participants who obtained abnormal results in at least two tests) and the group”C” (Control) including 132 participants without APD. The results obtained by 6-year-old children in behavioral tests present a similar disorder’s profile to those of older children in terms of the prevalence of specific deficits and their severity. Performance in the APD tests of healthy 6-year-old children is higher than 9-year-old children with APD, despite the process of physiological development of hearing functions in older children. The test assessing understanding speech in noise was the most frequently impaired among all examined, while the dichotic listening with distracted attention was the least frequently impaired function. The deficit found in DDT was opposite between patients with APD and healthy children, we called the detected phenomenon the reversed lateralization pattern. The use of DDT, FPT and ASPN-S tests to evaluate higher auditory functions in the process of diagnosing APD in 6-year-old children is justified by the lack of discrepancy in the disorder profile of 6-year-old children in comparison with older children, both in the healthy population, and in children with impaired auditory function development. Early diagnosis can be beneficial for accurate programming of therapeutic goals.
Most of the 19 mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) involved in mitochondrial protein synthesis are already linked to specific entities, one of the exceptions being PARS2 mutations for ...which pathogenic significance is not finally validated. The aim of the study was to characterize the PARS2- related phenotype.Three siblings with biallelic PARS2 mutations presented from birth with infantile spasms, secondary microcephaly, and similar facial dysmorphy. Mental development was deeply impaired with speech absence and no eye contact. A dilated cardiomyopathy and multiorgan failure developed in childhood at the terminal stage, together with mitochondrial dysfunction triggered by valproate administration.Brain MRI showed progressive volume loss of the frontal lobes, both cortical and subcortical, with widening of the cortical sulci and frontal horns of the lateral ventricles. Hypoplasia of the corpus callosum and progressive demyelination were additional findings. Similar brain features were seen in three already reported PARS2 patients and seemed specific for this defect when compared with other mt-aaRSs defects (DARS2, EARS2, IARS2, and RARS2).Striking resemblance of the phenotype and Alpers-like brain MRI changes with predominance of frontal cerebral volume loss (FCVL-AS) in six patients from three families of different ethnicity with PARS2 mutations, justifies to distinguish the condition as a new disease entity.
Auditory discrimination, the hearing ability crucial for speech and language development, allowing one to perceive changes in volume, duration and frequency of sounds, was assessed for 366 ...participants with normal peripheral hearing: 220 participants with auditory processing disorders (APD) and 146 typically developing (TD) children, all aged 6-9 years. Discrimination of speech was tested with nonsense words using the phoneme discrimination test (PDT), while pure tones-with the frequency pattern test (FPT). The obtained results were statistically analyzed and correlated. The median of the FPT results obtained by participants with APD was more than twice lower than those of TD (20% vs. 50%;
< 0.05), similarly in the PDT (21 vs. 24;
< 0.05). The FPT results of 9-year-old APD participants were worse than the results of TD 6-year-olds (30% vs. 40%;
< 0.05), indicating that the significant FPT deficit strongly suggests APD. The process of auditory discrimination development does not complete with the acquisition of phonemes but continues during school age. Physiological phonemes discrimination is not yet equalized among 9-year-olds. Nonsense word tests allow for reliable testing of phoneme discrimination. APD children require testing with PDT and FPT because both test results allow for developing individual therapeutic programs.
The aim was to describe the spectrum of inner ear malformations in CHARGE syndrome and propose a Computed Tomography (CT) detailed scan evaluation methodology. The secondary aim was to correlate the ...CT findings with hearing thresholds.
Twenty ears of ten patients diagnosed with CHARGE syndrome were subjected to CT analysis focusing on the inner ear and internal acoustic canal. The protocol used is presented in detail. ASSR results were analyzed and correlated with inner ear malformations.
Cochlear hypoplasia type III was the most common malformation found in 12 ears (60%). Cochlear hypoplasia type II, aplasia with a dilated vestibule, and rudimentary otocyst were also identified. In 20%, no cochlear anomaly was found. The lateral Semicircular Canal (SCC) absence affected 100% of ears, the absence of the posterior SCC 95%, and the superior SCC 65%. Better development of cochlea structures and IAC correlated significantly with the lower hearing thresholds.
This study demonstrated that rudimentary SCC or a complete absence of these SCCs was universally observed in all patients diagnosed with CHARGE syndrome. This finding supports the idea that inner ear anomalies are a hallmark feature of the CHARGE, contributing to its distinct clinical profile. The presence of inner ear malformations has substantial clinical implications. Audiological assessments are crucial for CHARGE syndrome, as hearing loss is common. Early detection of these malformations can guide appropriate interventions, such as hearing aids or cochlear implants, which may significantly improve developmental outcomes and communication for affected individuals. Recognizing inner ear malformations as a diagnostic criterion presents implications beyond clinical diagnosis. A better understanding of these malformations can advance the knowledge of CHARGE pathophysiology. It may also help guide future research into targeted therapies to mitigate the impact of inner ear anomalies on hearing and balance function.
4.
Recently, CLPB deficiency has been shown to cause a genetic syndrome with cataracts, neutropenia, and 3-methylglutaconic aciduria. Surprisingly, the neurological presentation ranges from completely ...unaffected to patients with virtual absence of development. Muscular hypo- and hypertonia, movement disorder and progressive brain atrophy are frequently reported. We present the foetal, peri- and neonatal features of 31 patients, of which five are previously unreported, using a newly developed clinical severity scoring system rating the clinical, metabolic, imaging and other findings weighted by the age of onset. Our data are illustrated by foetal and neonatal videos. The patients were classified as having a mild (
n
= 4), moderate (
n
= 13) or severe (
n
= 14) disease phenotype. The most striking feature of the severe subtype was the neonatal absence of voluntary movements in combination with ventilator dependency and hyperexcitability. The foetal and neonatal presentation mirrored the course of disease with respect to survival (current median age 17.5 years in the mild group, median age of death 35 days in the severe group), severity and age of onset of all findings evaluated. CLPB deficiency should be considered in neonates with absence of voluntary movements, respiratory insufficiency and swallowing problems, especially if associated with 3-methylglutaconic aciduria, neutropenia and cataracts. Being an important differential diagnosis of hyperekplexia (exaggerated startle responses), we advise performing urinary organic acid analysis, blood cell counts and ophthalmological examination in these patients. The neonatal presentation of CLPB deficiency predicts the course of disease in later life, which is extremely important for counselling.
Leigh syndrome (LS), subacute necrotizing encephalomyelopathy is caused by various genetic defects, including m.9185T>C
MTATP6
variant. Mechanism of LS development remains unknown. We report on the ...acid-base status of three patients with m.9185T>C related LS. At the onset, it showed respiratory alkalosis, reflecting excessive respiration effort (hyperventilation with low pCO
2
). In patient 1, the deterioration occurred in temporal relation to passive oxygen therapy. To the contrary, on the recovery, she demonstrated a relatively low respiratory drive, suggesting that a “hypoventilation” might be beneficial for m.9185T>C carriers. As long as circumstances of the development of LS have not been fully explained, we recommend to counteract hyperventilation and carefully dose oxygen in patients with m.9185T>C related LS.
Alpha-mannosidosis (AM) is a rare autosomal recessive lysosomal storage disease which the natural history has not been exhaustively described yet. The aim of this study was to present the long-term ...follow-up of 12 Polish patients with AM, evaluate the clinical, biochemical, and molecular findings and progression of the disease.
The article presents a long-term (over 30 years) observational, retrospective, single-center study of patients with AM.
The hearing loss, as one of the first symptoms, was detected in childhood (mean age of 2 years and 6 months) in 10 patients. The other symptoms include: recurrent infections (all patients), inguinal hernias (6 patients), craniosynostosis (1 patient). The mean age at AM diagnosis was 6 years while median was 4 years (age range: 1 year and 8 months – 12 years). The most commonly identified variant in the MAN2B1 gene was c.2245C > T, p.(Arg749Trp). The mean time of follow-up in our study was approximately 14years (range: 1 year – 26 years). Following birth, children with AM grow slowly, finally reaching the 3rd percentile (or values below the 3rd percentile). Hearing loss was not progressive while a gradual exacerbation of intellectual disability with no developmental regression was observed in all patients. Ataxia was diagnosed in 6 patients in the second decade of life (age range 15–20 years).
Our study revealed the sensorineural hearing loss as one of the first noted symptom in AM which was congenital and non-progressive during the natural course of disease. A detailed anthropometric phenotype of AM patients was provided with observation of the growth decline during the long-term follow-up. Our study confirmed the existence of two distinguished clinical phenotypes of AM (mild and moderate), and also the lack of clear genotype-phenotype correlation.
De novo somatic variants in genes encoding components of the PI3K–AKT3–mTOR pathway, including MTOR, have been linked to hemimegalencephaly or focal cortical dysplasia. Similarly to other ...malformations of cortical development, this condition presents with developmental delay and intractable epilepsy, often necessitating surgical treatment. We describe a first patient with the Smith–Kingsmore syndrome phenotype with recurrent hypoglycemia caused by low-level mosaic MTOR mutation restricted to the brain. We provide discussion on different aspects of somatic mosaicism. Deep exome sequencing combined with a variant search in multiple tissues and careful phenotyping may constitute a key to the diagnosis of the causes of rare brain anomalies.
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