EGYPT: The alarming childhood neurodevelopmental disorders situation is bringing neuroimaging genetics and community health into the ENGINES.

Dear colleagues,

Egypt is facing an alarming gap between innovations in childhood learning and developmental disabilities (LDD) research and their delivery to communities. This gap is now attaining public health significance. Egypt is the most populous country in the Middle East (~82 million inhabitants) with the highest rate (25-60%) of consanguinity through marriages (Alwan and Modell, 1997) most of them are cousin marriages (i.e., parental consanguinity). This high consanguinity rate results in complex LDD neurogenetic disorders (Temtamy et al., 1994). Birth incidence of malformations in Egyptian newborns ranges between 1.16 and 3.17% (Temtamy et al., 1994). In a study of 3000 consecutive neonates delivered in a maternity hospital in Cairo, parental consanguinity was found in 31.8% of all cases and in 55% of malformed cases, thus illustrating the effects of consanguinity and LDD (Temtamy et al., 1998). In another study, Mokhtar et al., (1998) studied 660 adult patients at the Medical Research Centre in Alexandria, and found that neurogenetic disorders were detected in 45.2%; of these 33.6% had autosomal recessive disorders, 13.4% had autosomal dominant disorders, 6.7% had X-linked disorders, 5.0% had multifactorial disorders, 8.4% had chromosomal abnormalities, 3.4% were due to teratogens and 19.5% were sporadic. A third study investigated 20,500 school-age Egyptian males and found a high fragile x syndrome (FXS) prevalence (~1/1000) (Meguid et al., 2007). Of note, FXS is the main cause of mental retardation and is estimated worldwide to be ~1/4000-8000 (Crawford et al. 2001). Furthermore, disorders of sex development with birth of an infant with ambiguous genitalia, is not uncommon in Egypt (1:3000 live-births). Consanguinity in this group has been estimated to ~61%. In addition, the frequently reported parental consanguinity emphasizes the major role of the single gene inheritance in Micro syndrome (microcephaly, mild microphthalmia, microcornea, congenital cataracts and hypogenitalism) (Abdel-Salam et al. 2007). Similarly, in Dandy-Walker malformation (brain stem dysgenesis and abnormal gyral pattern with psychomotor retardation) parents' consanguinity suggest an autosomal recessive inheritance pattern in Egypt (Abdel-Salam et al. 2006). Increased risk of congenital heart diseases among Down syndrome patients is significantly associated with parental consanguinity and maternal parents' consanguinity (Mokhtar and Abdel-Fattah 2001). Overall, LDD, partly due to consanguinity, constitute an enormous socio-emotional and financial burden on the Egyptian healthcare system and public.

Notwithstanding the preceding facts, the LDD alarming gap is growing and deepening, widening public fear and ignorance. On one hand, Egypt prioritizes the control and eradication of infectious diseases and reproductive, maternal health. On the other hand, LDD research in Egypt receives scant attention and almost no funding from donor agencies that specialize in addressing the problems of developing nations. In this context, we have developed the Egyptian Neuroimaging Genetics Initiative Network with Switzerland (ENGINES), which is urgently seeking your support. Indeed, LDD in Egypt mandate demands that we harness powerful public and scientific tools to achieve better understanding, treatment and ultimately prevention of these disabling childhood chronic conditions. The ENGINES will intervene on those underlying forces that challenge one of the most important global health issues (i.e., LDD), by establishing a scientific-public collaboration to develop and apply global health knowledge for evidence-informed policy and practice.

Therefore, the primary objective of the ENGINES is to develop, implement and sustain novel technologies, i.e., neuroimaging the genetics, cognition and behavior, for the diagnosis, characterization and treatment of LDD by integrating data from multiple levels of analyses.
I. ORGANIZE AN ANNUAL EGYPTIAN SCIENTIFIC-PUBLIC CONFERENCE: the title of the first conference would be: INVEST IN EGYPTIAN SCIENCE: Repair the Brain Campaign. The target audience will be politicians, businessmen, media representers, famous artists, families with children with LDD, general practitioners, pediatricians, neurologists, psychiatrists, psychologists, social workers, and special education personnel. The goal is to create ties between academia, industry and the Egyptian public, and provide a fertile environment for innovation and the practical application of new discoveries (i.e., translational medicine). This perspective will unite the financial generosity of the private sector with the scientific vision of translational medicine ensuring that breakthroughs in science become breakthroughs for children with LDD. The INVEST IN EGYPTIAN SCIENCE campaign will emphasize that working together will help Egyptians achieve the ENGINS goals (listed below). At this point, it is worth noting that taking into consideration Egypt’s history, geography, political and cultural impact in the region, we anticipate that the ENGINS vision will attract the interest and active participation of the public and scientists from all around the Middle East.

II. ESTABLISH TWO CHILDHOOD INTERDISCIPLINARY LEARNING AND DEVELOPMENTAL DISABILITIES (CHILD) centers within the ENGINS in Cairo and Alexandria (as a start then apply the CHILD centers to the remaining 27 governorates) to (i) ensure that a diverse and highly trained workforce is available to assume continued leadership roles; (ii) improve human health, by conducting translational research to translate LDD scientific discoveries into practical applications; and (iii) improve the Egyptian public awareness regarding LDD and medical research. The CHILD centers would enable Egyptian researchers to innovate in their own translational research efforts and to transform their own environment to promote the development and advancement of LDD translational medicine to serve the Egyptian public. The first CHILD center will be created at the National Research Center, Department of Children with Special Needs under the supervision of Dr. Nagwa Meguid in Cairo, and the second one will be created in Alexandria University, Faculty of Medicine, Department of Community Health under the supervision of Dr. Amira Seif Eldine. To work effectively, these CHILD centers will need a well-trained interdisciplinary task force of developmental psychologists, occupational and speech therapists, early child educators, social workers and biomedical engineers (Dr. Yasser Kadah from Cairo University, Faculty of Engineering). The CHILD centers, in close collaboration with the University of Lausanne (Drs. Fahim, Frackowiak and Jacquemont) and McGill University (Alan C. Evans) will achieve the following:

1) ASCERTAIN THE PREVALENCE OF LDD IN EGYPT: It is of primordial scientific and public importance to collect, classify and maintain accurate and comprehensive information on LDD in a high populated and genetically variant country as Egypt, taking into account its high consanguinity rate. Furthermore, such an epidemiological approach would allow us to gather specific medical, behavioral and socio-economic data (for example, cancer, obesity, genetic and environmental factors related to the disorders). Epidemiological data will be used to plan and evaluate prevention and treatment strategies. Moreover, the gathered epidemiological date would give us some clues to LDD possible etiological factors. Another significant contribution to the epidemiological part of the ENGINES project is the monitoring of time trends to show which disorders are increasing or decreasing in incidence and which are changing in their distribution. This information is needed to identify emerging problems. Noteworthy, we will respect and protect the right to privacy of the patient and ensure the appropriate use of this confidential health data.

2) BUILD THE EGYPTIAN PUBLIC TRUST IN THE ENGINES: by building relationships with patients: Listen to family concerns. Compassion in LDD science is desperately needed: to treat patients and their families with empathy (as a person, not a subject number). To have their privacy/confidentiality protected. To let them hear about the study results. Focus on educational strategies to help patients and communities better understand LDD. Parents of children with LDD exhibit some health and psychosocial problems. While addressing children’s behavior problems, CHILD center professionals should also consider the family physical and psychosocial health, as this may also have an impact on LDD children’s welfare.

3) BUILD THE EGYPTIAN GENRAL PRACTITIONERS TRUST IN THE ENGINS: Educating local physicians (GPs) about LDD and the CHILD centers by teaching and developing course materials for science and education. This step would allow a wider Egyptian scientific community to play a role in the scientific-public awareness, which is an integral part of the ENGINES process. For example, GPs education will improve early detection with proper diagnosis and provide parents with important information about future reproductive risks.

4) CREATE, ADVOCATE FOR AND IMPLEMENT LDD NEUROREHABILITATION AS A TREATMENT:
• Advocate for and insist on children with LDD access to quality preschool interventions nationwide.
• Apply Cognitive Rehabilitation for Children with LDD (i.e., verbal understanding, socio-emotional understanding, joint attention, and nonverbal cognition) in the CHILD centers.
• Apply Motor and Sensory Rehabilitation for Children with LDD in the CHILD centers.
• Family education and support systems for all children with LDD in the CHILD and local community centers.


In essence, the ENGINES will pool knowledge and resources to bridge the LDD gap in Egypt, a bridge, which will ultimately be extended to other Middle Eastern countries. In addition to building the infrastructure to support LDD clinical and translational research, the ENGINES acknowledges the impact and importance of scientific-public collaboration and the need for an integrated international policy and strategy to tackle the alarming LDD public health situation, thus multiplying the impact of our philanthropy.

Sincerely,
Cherine FAHIM, Ph.D