Ahmed Alaqeel

Accelerating matchmaking of novel dysmorphology syndromes through clinical and genomic characterization of a large cohort

Purpose:Dysmorphology syndromes are among the most common referrals to clinical genetics specialists. Inability to match the dysmorphology pattern to a known syndrome can pose a major diagnostic challenge. With an aim to accelerate the establishment of new syndromes and their genetic etiology, we describe our experience with multiplex consanguineous families that appeared to represent novel autosomal recessive dysmorphology syndromes at the time of evaluation.Methods:Combined autozygome/exome analysis of multiplex consanguineous families with apparently novel dysmorphology syndromes.Results:Consistent with the apparent novelty of the phenotypes, our analysis revealed a strong candidate variant in genes that were novel at the time of the analysis in the majority of cases, and 10 of these genes are published here for the first time as novel candidates (CDK9, NEK9, ZNF668, TTC28, MBL2, CADPS, CACNA1H, HYAL2, CTU2, and C3ORF17). A significant minority of the phenotypes (6/31, 19%), however, were caused by genes known to cause Mendelian phenotypes, thus expanding the phenotypic spectrum of the diseases linked to these genes. The conspicuous inheritance pattern and the highly specific phenotypes appear to have contributed to the high yield (90%) of plausible molecular diagnoses in our study cohort.Conclusion:Reporting detailed clinical and genomic analysis of a large series of apparently novel dysmorphology syndromes will likely lead to a trend to accelerate the establishment of novel syndromes and their underlying genes through open exchange of data for the benefit of patients, their families, health-care providers, and the research community.Genet Med 18 7, 686–695.

Epilepsy; what do Saudi's living in Riyadh know?

PURPOSE Epilepsy is very common in the Kingdom of Saudi Arabia, with a prevalence of 6.54 per 1000. The present study was conducted to investigate the level of public awareness, and the attitudes and knowledge regarding epilepsy in the Saudi population in Riyadh - capital city of Saudi Arabia. METHODS A survey consisting of 19 questions pertaining to epilepsy awareness was distributed to Saudi citizens living in Riyadh older than 15 years of age in malls, supermarkets, health clubs, mosques, universities and schools. RESULTS Of the 7078 respondents who completed the questionnaire, 6756 (95.5%) had heard about epilepsy, 3024 (42.7%) had witnessed what they believed to be a seizure and 5164 (73%) would allow their children to interact with an individual who had epilepsy. However, 5382 (76%) respondents would not want their children to marry an individual with epilepsy, 1004 (14.2%) believed that epilepsy was infectious and 574 (8.1%) believed that epilepsy was a type of mental illness. A total of 1509 (21.3%) respondents were not aware of a single potential cause of epilepsy, 3493 (50.6%) would not seek medical advice if one of their relatives had epilepsy, 2221 (31.4%) did not know how to deal with an individual experiencing an epileptic episode and 6554 (92.6%) did not know that surgery was a treatment option for individuals with epilepsy in Saudi Arabia. Of the 7078 respondents, 3237 (45.7%) would not abide by a physicians advice not to operate a motor vehicle because of their illness, of whom 1631 (50.4%) cited problems with the public transportation system as a reason for disregarding the doctors advice. The effect of age and level of education were statistically significant on most of the study variables. CONCLUSION The level of epilepsy awareness in the Saudi population needs improvement.

Epilepsy: What do health-care professionals in Riyadh know?

PURPOSE The objective of this study was to report on the knowledge of epilepsy, as well as attitudes and practices toward individuals with epilepsy, among health-care professionals in Riyadh, the capital city of Saudi Arabia. METHODS A survey consisting of 23 questions pertaining to epilepsy awareness was distributed to health education workers (n=51), nutritionists (n=56), physicians (n=265), dentists (n=58), pharmacists (n=41), nurses (n=224), physiotherapists (n=65), and fifth-year medical students (n=62) in three tertiary hospitals in Riyadh. RESULTS Of the 822 respondents who completed the questionnaire, 100% had heard about epilepsy, and 92.6% would allow their children to interact with an individual who has epilepsy. However, 67% of respondents would not want their children to marry an individual with epilepsy, 97.9% of respondents believed that individuals with epilepsy should have the same employment opportunities as the general population, 10.5% believe that supernatural power is the cause of epilepsy, 67.2% did not know how to deal with an individual experiencing an epileptic episode, and 56% did not know that surgery was a treatment option for individuals with epilepsy in Saudi Arabia. Of the 822 respondents, 39% would not abide by a physicians advice not to operate a motor vehicle because of their illness, 91% of whom cited problems with the public transportation system as a reason for disregarding the doctors advice. When asked if the participants had access to any information on how to deal with epilepsy during their professional training, 60.3% had access to such information during their graduate studies. Ninety-eight percent of those with access to this information were physicians and health-care educators (p<0.001). Physicians and health-care educators were significantly more aware of epilepsy than any of the other groups. CONCLUSION The level of epilepsy awareness among health-care professionals in Riyadh needs improvement.

T (brachyury) is linked to a Mendelian form of neural tube defects in humans

A large consanguineous family in which four members were born with isolated myelomeningocele was recruited as part of our ongoing effort to characterize Mendelian phenocopies of complex disorders (KFSHRC IRB Protocol #2121053) (Fig. 1a). Only one region of homozygosity (ROH) shared by the four affected members of the family was identified on chromosome 6 (163,540,399– 166,657,970), and linkage analysis confirmed this locus and assigned it a significant LOD score of 4.5 (Fig. 1b, c). Exome sequencing of one of the affected members produced full coverage of all coding sequences within the linkage interval but only one homozygous novel missense variant was identified therein. This variant (NM_003181.3: c.466G>T; p.Gly156Cys) is in T (Fig. 1d), the murine homologue of which has been shown to be important for the formation and differentiation of the mesoderm and the axial development (Abe et al. 2000). The affected Gly156 residue is invariant in humans (as per 1000 Genomes and ExAC Browser) and vertebrates down to Zebrafish, and resides within the highly conserved T-box (Fig. 1e, f). It is also highly predicted to be pathogenic based on PolyPhen (0.999) and SIFT (0), and is absent in >600 in-house Saudi exomes, 173 Saudi controls (including 83 from the same tribe) by direct sequencing, and in the Exome Variant Server (EVS). Nine unaffected siblings as well as the parents were also recruited in this family and the novel variant was sequenced to check segregation. The variant was heterozygous or absent in the parents and six unaffected siblings; however, three of the unaffected siblings were homozygous to this variant. X-ray examination of the spine of those apparently non-penetrant individuals showed that one of them (VII:1) has spina bifida occulta, while the other two did not have gross abnormalities although it was not possible to conduct MRI/CT examination of the spine to conclusively confirm non-penetrance. To The Editor,

Stroke Awareness in the Saudi Community Living in Riyadh: Prompt Public Health Measures Must Be Implemented

BACKGROUND Stroke is very prevalent in the Kingdom of Saudi Arabia, approaching 43.8 per 100,000 people. Stroke outcome is known to be affected by the level of stroke awareness in the community. We conducted this study to assess the level of stroke awareness in the Saudi population. METHODS A validated survey of 11 questions was used to assess the level of stroke awareness among the Saudi population. The survey was distributed in a 1-month period to every adult Saudi citizen visiting 10 shopping centers, 10 large supermarkets, 4 hospitals, and 2 universities. RESULTS Two thousand eight hundred sixty-two people completed the questionnaire (a 78% response rate). One thousand eight hundred forty-four people (64%) were able to define stroke correctly. One thousand four hundred twenty-eight people (49.9%) named mass media as the source of their knowledge. One thousand three hundred one (45.9%) believe stroke and brain death share the same pathologic mechanism and outcome, particularly those <40 years of age (P < .05). Six hundred twenty-two (21.7%) of the respondents correctly chose ≥5 risk factors and made ≤1 error. Five hundred twenty-seven (18.4%) of the participants in this study were able to correctly identify ≥3 symptoms of the list and make ≤1 error. CONCLUSIONS There is an alarming deficit in the level of stroke awareness in the Saudi population. Urgent public health measures to correct this deficiency are promptly needed.

Causes and patterns of adult traumatic head injuries in Saudi Arabia: implications for injury prevention.

BACKGROUND AND OBJECTIVES Data on the epidemiology of traumatic head injuries (THI) is essential for any organized prevention program. Such data are few in the developing world. Our primary goal was to study the causes, descriptive features, and outcomes of THI in adults in Saudi Arabia. DESIGN AND SETTINGS The present study is a retrospective review. METHODS This retrospective review included all consecutive cases of adults with THI (>18 years) who were admitted to a major trauma centre in Riyadh, Saudi Arabia, from May 2001 to July 2010. Patients were identified through a trauma database, which includes cases that required hospital admission or died in the emergency department. RESULTS A total of 1870 patients met the inclusion criteria with a mean age of 32.6 years and a male predominance (91.2%). Most injuries were secondary to motor vehicle collisions (MVC; 69.4%). Pedestrian injuries were second (16.8%) and had 40% risk of mortality (odds ratio 0.62, 95% CI 0.48–0.8). Most patients (56.7%) had a severe THI (Glasgow coma score, GCS < 8). The overall mortality rate was 30%. Mortality was significantly associated with older age (P=.0001), lower GCS (P=.0001), and a higher injury severity score (ISS; P=.0001). CONCLUSION The most common causes of hospital admission following injury were MVC and pedestrian injuries. Both were also the most common causes for injury-related deaths. Safety on the roads should be the primary target for any organized injury prevention programs to be successful.

Causes and patterns of spine trauma in children and adolescents in Saudi Arabia: implications for injury prevention

BACKGROUND AND OBJECTIVES Knowledge regarding traumatic spine injuries (TSIs) is essential for effective prevention strategies, particularly in the developing world, where majority of the population is younger and organized prevention programs are scarce. Therefore, our objective was to describe TSI mechanisms, demographics, patterns, and outcomes in children and adolescents. DESIGN AND SETTINGS Retrospective chart review in a major trauma center from May 2001 to May 2009 in Riyadh, Saudi Arabia. PATIENTS AND METHODS Detailed chart reviews were done for all consecutive TSI patients ≤18 years old. Cases were identified through the trauma database registry that included admitted patients. RESULTS Of the 3796 cases identified, 120 cases (3.2%) sustained 141 TSIs (mean age: 13.5 years; males: 83.8%). TSI was most common among children from 16 to 18 years old. Overall, motor vehicle collision (MVC) was the most common injury mechanism (60.8%). However, younger patients (<12 years) sustained more pedestrian injuries (40.6%). Among MVC cases with known seat belt statuses (43.8%), 90.6% were not wearing seat belts. The cervical spine level was the most commonly affected (55.8%) region, especially in children <12 years old (88%). More than 1 affected spinal level was found in 23.3% cases. Spinal cord injuries were found in 19.2% cases. Overall, mortality was 8.3%, and half of these mortalities were secondary to pedestrian injuries. A total of 22.7% of cases were discharged with neurological deficits. CONCLUSION The high frequency and severity of MVC and pedestrian injuries observed in the present study raise significant concerns regarding the safety of children on the roads. Spine involvement was age specific; younger patients tended to have more cervical injuries, and older patients exhibited more thoracic spine involvement.

Focal brainstem gliomas Advances in intra-operative management

Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals.