Sahar Saleem

OBJECTIVE: To identify causes of the autosomal-recessive malformation, diencephalic-mesencephalic junction dysplasia (DMJD) syndrome.

METHODS: Eight families with DMJD were studied by whole-exome or targeted sequencing, with detailed clinical and radiological characterization. Patient-derived induced pluripotent stem cells were derived into neural precursor and endothelial cells to study gene expression.

RESULTS: All patients showed biallelic mutations in the nonclustered protocadherin-12 (PCDH12) gene. The characteristic clinical presentation included progressive microcephaly, craniofacial dysmorphism, psychomotor disability, epilepsy, and axial hypotonia with variable appendicular spasticity. Brain imaging showed brainstem malformations and with frequent thinned corpus callosum with punctate brain calcifications, reflecting expression of PCDH12 in neural and endothelial cells. These cells showed lack of PCDH12 expression and impaired neurite outgrowth.

INTERPRETATION: DMJD patients have biallelic mutations in PCDH12 and lack of protein expression. These patients present with characteristic microcephaly and abnormalities of white matter tracts. Such pathogenic variants predict a poor outcome as a result of brainstem malformation and evidence of white matter tract defects, and should be added to the phenotypic spectrum associated with PCDH12-related conditions. Ann Neurol 2018;84:646-655.

Ancient Egypt had an advanced elaborate medical education and practice ruled by a competent bureaucracy that apprenticed physicians to be practicing healers. In modern history, the Faculty of Medicine at Cairo University (Kasr Al-Ainy), established in 1827, continues the glory of Egypt in medical education as one of the biggest and oldest medical schools in Africa and the Middle East. Its central Radiology Department, with its total 77 radiologists, is responsible for clinical services as well as for providing multiple calibre radiology education programs for about 100 trainees annually from Egypt and neighbouring countries. Radiology education programs are planned for radiology residents to obtain master’s degree (M.Sc.), for assistant lecturers to obtain medical doctorate (M.D.) and for visitor trainees. Objectives of radiology education programs include knowledge, practical skills, intellectual capabilities and communications with medical societies and communities. Trainees are assessed to determine if learning objectives have been fulfilled on a daily, weekly and biannual basis. Radiology education programs are measured for professional performance through the university’s self-assessment studies; national assessment is measured through the National Authority for Quality Assurance and Accreditation in Education (NAQAAE), Egypt, and international assessment is measured through the World Federation for Medical Education (WFME).