Marwa Saleh

Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield

Intellectual disability (ID) is a measurable phenotypic consequence of genetic and environmental factors. In this study, we prospectively assessed the diagnostic yield of genomic tools (molecular karyotyping, multi-gene panel and exome sequencing) in a cohort of 337 ID subjects as a first-tier test and compared it with a standard clinical evaluation performed in parallel. Standard clinical evaluation suggested a diagnosis in 16% of cases (54/337) but only 70% of these (38/54) were subsequently confirmed. On the other hand, the genomic approach revealed a likely diagnosis in 58% (n=196). These included copy number variants in 14% (n=54, 15% are novel), and point mutations revealed by multi-gene panel and exome sequencing in the remaining 43% (1% were found to have Fragile-X). The identified point mutations were mostly recessive (n=117, 81%), consistent with the high consanguinity of the study cohort, but also X-linked (n=8, 6%) and de novo dominant (n=19, 13%). When applied directly on all cases with negative molecular karyotyping, the diagnostic yield of exome sequencing was 60% (77/129). Exome sequencing also identified likely pathogenic variants in three novel candidate genes (DENND5A, NEMF and DNHD1) each of which harbored independent homozygous mutations in patients with overlapping phenotypes. In addition, exome sequencing revealed de novo and recessive variants in 32 genes (MAMDC2, TUBAL3, CPNE6, KLHL24, USP2, PIP5K1A, UBE4A, TP53TG5, ATOH1, C16ORF90, SLC39A14, TRERF1, RGL1, CDH11, SYDE2, HIRA, FEZF2, PROCA1, PIANP, PLK2, QRFPR, AP3B2, NUDT2, UFC1, BTN3A2, TADA1, ARFGEF3, FAM160B1, ZMYM5, SLC45A1, ARHGAP33 and CAPS2), which we highlight as potential candidates on the basis of several lines of evidence, and one of these genes (SLC39A14) was biallelically inactivated in a potentially treatable form of hypermanganesemia and neurodegeneration. Finally, likely causal variants in previously published candidate genes were identified (ASTN1, HELZ, THOC6, WDR45B, ADRA2B and CLIP1), thus supporting their involvement in ID pathogenesis. Our results expand the morbid genome of ID and support the adoption of genomics as a first-tier test for individuals with ID.

Fundamental Frequency Stability in Functional Dysphonia

Functional dysphonia is a term applied to voice disorders for which there is an absence of apparent structural change in the larynx. The aim of this work was to investigate how functional dysphonia may differ acoustically from other types of dysphonia. Fundamental frequency profiles for steady vowels were generated using a software program called GLIMPES (Glottal Imaging by Processing External Signals). The fundamental frequency variations were found to be unimodal in normal individuals. In contrast, the variations for dysphonic patients were sometimes bi-modal or multi-modal due to the presence of subharmonics or low-frequency modulations. The appearance of these patterns was generally related to the severity of the dysphonia rather than to its etiology.

Early Phonological Development in Arabic Egyptian Children: 12–30 Months

Phonological development is a dynamic process that operates on three levels: universal development, specific language development, and specific child development. An intricate relationship between the three factors delineates the course of acquisition of each child’s phonemic inventory. This study is designed to investigate the phonemic inventory and the phonological processes used by Arabic Egyptian children in order to evaluate cross-linguistic similarities and differences. Thirty Egyptian children with Cairene dialect, in the age period between 12 and 30 months, were included and divided into three groups, each covering a 6-month interval. A 1-hour tape recording for each child was done, followed by analysis of the phonemic inventory and phonological processes. Phonemic inventories showed universal similarities, with frequent occurrence of stops, nasals, and glides mostly in the form of bilabial and alveolar sounds. This is besides a specific tendency for early frequent production of laryngeal phonemes. Glottal replacement was found to be a common and naturally occurring phonological process, leading to frequent occurrence of glottal stop /U/ in the inventories of Egyptian children. The final position of the word showed the highest degree of correct phoneme production.

The Arabic Vowels: Features and Possible Clinical Application in Communication Disorders

Most scholars, old and modern, agree that the vowel system of the Arabic language is composed of 3 vowels only, namely /i/, /Ε/ and /u/. The spoken Cairo dialect suggests that there are 6 identifiable vowels, with a short and long variant for each. Objective: The aim of this study is to test the validity of the notion that there are 6 × 2 distinct vowels, with a more central one. Subjects and Methods: Spectral analysis was used to measure F1 and F2 for the vowels of 14 real words. Data was collected from 60 healthy adult informants, 30 males and 30 females. They were native Egyptians speaking the colloquial Cairene dialect. Results: The values of the 6 long and short vowels plus the central one are presented. A significant difference was found between each of them. The long and short vowels differed only in the duration but did not differ in their formant values. Conclusion: The study illustrates the distinctive features of the vowels of the Arabic language. Each of the 7 vowels represents a distinct entity. This will have important implications in assessment and management of language, speech and voice disorders in children and adults.

Spectrographic analysis of Egyptian Cairene /r/: Is it a trill or a tap?

Abstract The /r/ phoneme is variable in manner and place of articulation, and difficult to correct worldwide. Variability could exist within the same language. The objective of this study was to determine whether Egyptian Cairene /r/ was a trill or a tap and, if both forms were present, whether they were affected by word position or adjacent vowels/consonants. The information obtained was intended to improve correction of /r/ in faulty articulation. Spectrographic analysis was done for 50 Cairene subjects, who produced /r/ in different word positions in carrier phrases. Results have shown presence of both forms in the speech of every subject, but taps were more common than trills. Trills were more common in geminated /r/, in word-medial syllable final position, especially when preceded with /e/, /æ/ or /α/, and in word-medial syllable initial position, especially when preceded by non-back consonants.

Oropharyngeal Dysphagia and Diabetes Mellitus: Screening of 200 Type 1 and Type 2 Patients in Cairo, Egypt

Background: Although diabetes mellitus is a well-researched systemic endocrinal disease, literature is scarce addressing the co-occurrence of oropharyngeal dysphagia with diabetes. Objective: The aim of this work was to screen Egyptian diabetic patients for symptoms suggestive of oropharyngeal dysphagia using the validated Arabic version of the Eating Assessment Tool (A-EAT-10). Participants and Methods: 200 Egyptian adult diabetic patients, aged from 18 to 59 years participated in the study. The inclusion criteria were being diabetic patients of type 1 or type 2. Patients were asked to complete the A-EAT-10 questionnaire. Results: Age progression and being female were found to be risk factors for dysphagia among diabetic patients participating in this study. The most common symptom among diabetic patients who complained of dysphagia was “I cough when I eat.” Conclusion: The present study suggests the presence of oropharyngeal swallowing problems among patients with diabetes mellitus.

Development and Standardization of a Test for Pragmatic Language Skills in Egyptian Arabic: The Egyptian Arabic Pragmatic Language Test (EAPLT)

Objective: The aim of this study was to standardize an Egyptian Arabic Pragmatic Language Test (EAPLT) using linguistically and socially suitable questions and pictures in order to be able to address specific deficits in this language domain. Participants and Methods: Questions and pictures were designed for the EAPLT to assess 3 pragmatic language subsets: pragmatic skills, functions, and factors. Ten expert phoniatricians were asked to review the EAPLT and complete a questionnaire to assess the validity of the test items. The EAPLT was applied in 120 typically developing Arabic-speaking Egyptian children (64 females and 56 males) randomly selected by inclusion and exclusion criteria in the age range between 2 years, 1 month, 1 day and 9 years, 12 months, 31 days. Children’s scores were used to calculate the means and standard deviations and the 5th and 95th percentiles to determine the age of the pragmatic skills acquisition. Results: All experts have mostly agreed that the EAPLT gives a general idea about children’s pragmatic language development. Test-retest reliability analysis proved the high reliability and internal consistency of the EAPLT subsets. A statistically significant correlation was found between the test subsets and age. Conclusion: The EAPLT is a valid and reliable Egyptian Arabic test that can be applied in order to detect a pragmatic language delay.

Videokymographic Visualization of Phonasthenia: A Nonorganic Voice Disorder

Background: Phonasthenia is a voice disorder where the larynx looks essentially normal and dysphonia is not heard but felt by the patient. This study aims to use videokymography (VKG) to detect any abnormalities in the vibratory pattern in phonasthenia and to find out whether or not these abnormalities change after vocal loading. Methods: Thirty-seven phonasthenic patients and 31 normal subjects participated in a detailed protocol, including analysis of subjective complaints and videokymographic quasi-objective parameters (baseline) followed by loading their voices through prolonged loud reading for 45 min. A second evaluation (experimental) was done after loading. Results: Before vocal loading, patients had significantly more symptoms in all questionnaire questions and higher maximum width difference in VKG than controls. When pre- and postloading values were compared, both groups experienced more symptoms after loading (significant in most of the questions), while the pre- and post-VKG parameters did not show significant differences neither in patients nor controls. On comparing their percent change, the only statistically significant difference between the 2 groups was a greater change in the total score of the questionnaire in the control group. Conclusion: Patients had more vocal fatigue symptoms and more amplitude asymmetry between left and right vocal folds than normal subjects.

MRI Surface-Based Brain Morphometry in Egyptian Autistic and Typically Developing Children

Objectives: The verbal abilities of autistic children differ from those of typically developing ones and they also differ among autistic children themselves. Neuroanatomical changes and an abnormal organization of functional networks are expected to accompany such a neurodevelopmental disorder. The aim of this study was to delineate the brain neuroanatomical changes in Egyptian children with autism and to compare them with previous studies in order to add more insight into the global brain imaging deviations linked to autism. Patients and Methods: Twenty-five autistic children and 25 typically developing children underwent MRI. Further analysis was performed using surface-based morphometry to obtain cortical thickness, brain volume, and cortical complexity. Results: MRI analysis results revealed significantly greater cortical thickness, cortical complexity, and gray matter volume in the autistic as compared to the control group. On the other hand, the white matter volume was significantly smaller. Conclusion: These findings generally align with findings in previous studies, except for occasional differences.