NR4A2, a member of the nuclear receptor superfamily, is involved in modulation of target gene transcription, regulating several developmental processes such as regulation of cellular homeostasis, ...neuronal development, inflammation and carcinogenesis. 2q24.1 deletions are extremely rare, and only 1 patient with a de novo deletion encompassing only NR4A2 gene was reported so far. We report 3 additional patients with a de novo deletion encompassing NR4A2: 2 patients have deletions encompassing only NR4A2 gene and 1 patient has a deletion including NR4A2 and the first exon of GPD2. Our patients presented a neurodevelopmental disorder including language impairment, developmental delay, intellectual disability and/or autism spectrum disorder. We suggest that NR4A2 haploinsufficiency is implicated in neurodevelopmental disorder with high penetrance.
Duarte galactosemia is not classic galactosemia, but rather an example of biochemical variant galactosemia that results in approximately 25% residual activity of galactose-1-phosphate ...uridylyltransferase (GALT) enzyme. In contrast, classic galactosemia is associated with complete or near complete absence of GALT activity. While infants with classic galactosemia are placed on galactose-restricted diets to prevent the acute and long-term manifestations of their metabolic disorder, while individuals with Duarte variant galactosemia (Duarte-2 galactosemia) do not require diet therapy. The long-term complications that are seen in classic galactosemia such as cerebellar ataxia, and hypergonadotropic hypogonadism do not occur in Duarte-2 galactosemia. While Duarte galactosemia does not appear to be a metabolic disease, it may have an impact on early neurodevelopmental outcomes.
This study examined developmental outcomes and the need for special services in individuals with Duarte-2 galactosemia in comparison to individuals with classic galactosemia. We performed a medical record review of individuals with GALT deficiency who were evaluated at Boston Children's Hospital and enrolled in our study of outcomes in galactosemia. This included 95 participants, 21 with Duarte-2 galactosemia and 73 with classic galactosemia. Duarte-2 participants had developmental test scores within the average range. However, 42% of subjects with Duarte-2 galactosemia had participated in early intervention and/or special education and 32% received speech therapy. Their pattern of strengths and weaknesses in cognitive/language/motor domains was similar to that noted in participants with classic galactosemia, albeit to a milder degree. The data indicate that in children with Duarte-2 variant galactosemia, the cognitive/language and motor skills were within normal limits with their cognitive/language skills developing earlier than their motor skills during their first year of life. A history of diet treatment was not related to the use of special services. These results suggest that Duarte-2 galactosemia increases the risk for early mild developmental delays irrespective of treatment history, which resolves over time, and highlights the need to further assess neurodevelopment in early infancy, in Duarte-2 galactosemia. As Duarte-2 galactosemia is not a bona fide biochemical genetic disease, we hypothesize that elements in the genomic space that include the GALT gene are responsible for a transient delay in language-related motor skills during early infancy.
Introduction
Auditory neuropathy spectrum disorder (ANSD) is a distinct type of SNHL that is characterized by the presence of otoacoustic emissions and/or cochlear microphonics. Cochlear implantation ...was initially not recommended for ANSD children, later studies showed variable outcomes among ANSD. CI is currently the intervention option of choice for many children with ANSD who are unable to obtain benefit from conventional amplification.
Aim and Objectives
To review experiences with some of the preoperative and postoperative findings in a child who was diagnosed with auditory neuropathy and provided with cochlear implant. To describe changes in auditory function, which enabled to have significant improvement in hearing and communication skills through auditory verbal therapy (AVT) and regular follow ups.
Study Design
Pre and postoperative, findings in cochlear implant recipient who was diagnosed with ANSD. Child received complete medical examinations, including related consultations in audiology, otorhinolaryngology, paediatrics, neurology, psychology, speech language pathology, and radiology.
Methodology/Case Report
A 3-year-old-female have brought to the hospital with a C/o not responding to sounds, name call and unable to speak. Medical and Audiological evaluations were initiated. The hearing assessments of the child included appropriate behavioural audiometric techniques, objective measures of middle ear function, acoustic reflex studies, transient evoked (TEOAE), distortion product (DPOAE) otoacoustic emissions and auditory brainstem responses (ABR). Implanted with (HiRes Ultra CI HiFocus SlimJ Electrode), and objective measures were recorded intraoperatively electrode impedances and neural response telemetry (NRT) to assess the outcomes technically. These intraoperative objective measures were used to help program the speech processor for the child. Postoperatively, child has had regular follow-up with otorhinolaryngologist to assure complete healing of the surgical incision, to assess their general medical conditions, and audiologist for switch-on (speech processor) followed by mapping. The hearing and communication skills have been assessed, also continued Auditory Verbal Therapy (AVT) on a regular basis. Postoperatively, objective measures were recorded in regular intervals and monitored with therapy outcomes.
Results
The child has shown significant improvement in sound detection, speech perception abilities, communication skills and shown evidence of progression of good NRT results, which were recorded and had no postoperative complications.
Conclusion
Experience with cochlear implantation for child diagnosed with ANSD that effectively received and benefited from CI. A detailed and careful evaluations, audiological follow-ups and tailored rehabilitation plans, can be considered as a beneficial management approach for CI, especially who diagnosed with ANSD. The regular use of cochlear implant in this diagnosis can lead to a clear increase in speech comprehension, development and overall progress in quality of life. Success or lack of success with a CI appears to be somewhat dependent on the specific site of lesion (pre- or post-synaptic). Currently there are no clinical measures available to diagnose the specific site of lesion. Indeed, CI appears to be an effective rehabilitation modality for ANSD patients. This may be explained by the fact that the implanted electrode delivers synchronized electrical impulses directly to the auditory nerve, bypassing the presynaptic IHCs and its synapse involved in the unsynchronized firing of the auditory nerve described in ANSD. However, genetic studies that have proven to be essential in the knowledge of underlying mechanisms of ANSD represent a promising therapeutic approach in the management of ANSD.
Abstract Objective Auditory Verbal Therapy (AVT) is one of the primary treatment approaches for developing spoken language in children with hearing impairment (HI), but its outcomes have not been ...thoroughly investigated. The current study aimed to systematically review past studies investigating AVT outcomes in children with HI. Methods A systematic search was conducted in six databases. Fourteen articles that met the final inclusion criteria were grouped under three categories based on the outcome measures: receptive and expressive language development, auditory/speech perception and mainstreaming. Results Articles under “receptive and expressive language development” category indicated AVT can even help children with HI beyond three years of age to develop age appropriate language skills and catch up with their hearing peers. Articles under “auditory /speech perception” category suggested that children receiving AVT can learn to recognize words accurately even in presence of background noise. Articles grouped under “mainstreaming” category indicated that children receiving AVT can be successfully mainstreamed. Conclusion Although studies suggest that AVT can have a positive impact on developing speech and language skills in children with HI, it is difficult to generalize these findings due to limited evidence. Future studies should utilize well-controlled group designs to minimize the role of external variables as well as strengthen the evidence-base for AVT.
Ephrin receptor and their ligands, the ephrins, are widely expressed in the developing brain. They are implicated in several developmental processes that are crucial for brain development. Deletions ...in genes encoding for members of the Eph/ephrin receptor family were reported in several neurodevelopmental disorders. The ephrin receptor A7 gene (EPHA7) encodes a member of ephrin receptor subfamily of the protein‐tyrosine kinase family. EPHA7 plays a role in corticogenesis processes, determines brain size and shape, and is involved in development of the central nervous system. One patient only was reported so far with a de novo deletion encompassing EPHA7 in 6q16.1. We report 12 additional patients from nine unrelated pedigrees with similar deletions. The deletions were inherited in nine out of 12 patients, suggesting variable expressivity and incomplete penetrance. Four patients had tiny deletions involving only EPHA7, suggesting a critical role of EPHA7 in a neurodevelopmental disability phenotype. We provide further evidence for EPHA7 deletion as a risk factor for neurodevelopmental disorder and delineate its clinical phenotype.
Mapping of the 6q16.1 deletions encompassing EPHA7 (highlighted in blue) in our patients (red bar). Four out of 12 patients have deletions encompassing only EPHA7 and share a similar phenotype, suggesting the role of EPHA7 deletion as a risk factor for neurodevelopmental disorder with developmental delay/intellectual disability, speech delay, behavioral anomalies, and/or microcephaly. The deletions were inherited in nine out of 12 patients, suggesting variable expressivity and incomplete penetrance.
Non‐recurrent deletions in 2q24.1, minimally overlapping two genes, NR4A2 and GPD2, were recently described in individuals with language impairment and behavioral and cognitive symptoms. We herewith ...report on a female patient with a similar phenotype of severe language and mild cognitive impairment, in whom we identified a de novo deletion covering only NR4A2. NR4A2 encodes a transcription factor highly expressed in brain regions critical for speech and language and implicated in dopaminergic neuronal development. Our findings of a de novo deletion of NR4A2 in an individual with mild intellectual disability and prominent speech and language impairment provides further evidence for NR4A2 haploinsufficiency being causative for neurodevelopmental and particularly language phenotypes.
The way a young child uses language has an impact on their future life. Early language acquisition is a determinant in adult employment, mental health and relationships with others. At the same time ...there is a broad evidence base that play and learning in the natural environment is beneficial for young children's physical, emotional, social and cognitive development. However, literature about how these two contributions to children's early development intersect and combine, in particular whether and how early language learning in children aged between 3 and 7 years might be enhanced in nature, is harder to find. For this paper, we undertook a systematic literature review to explore and report on research within this important area. Based on an in-depth study of 181 articles, we found that scant literature exists about how children's language is developed within natural environments. Although this appears to be a topic that is discussed in practice-oriented publications, it was found that very few researchers are focusing on and reporting within this area. Twelve papers were thoroughly analysed and three themes identified and discussed; desire to communicate, communication skills and literacy skills. This paper concludes by suggesting areas for future research.