Holoprosencephaly spectrum among Egyptian patients: clinical and cytogenetic study

We report 24 patients with holoprosencephaly (HPE) spectrum screened for Del 7q36 and subtelomere 13q. They were divided according to the type of HPE into: 6 alobar, 15 semilobar, 1 lobar and 2 middle interhemispheric variant (MIH). All patients presented with global developmental delay. Microcephaly was in 83.3% and midfacial developmental defects were in the form of; cyclopia, arrhinia and agnathia in 2 patients (8.3%), premaxillary agenesis in 2 patients (8.3%), cleft lip and palate in 7 patients (29.2%), hypotelorism in 8 patients (33.3%) and hypertelorism in 9 patients (37.5%). The neurological deficits were as follows: abnormal tone and spasticity were present in all of them with exceptional of a single patient with MIH who presented with hypotonia and was able to walk independently at the age of 3 years, athetoid and/or dystonic movements of limbs in 22 patients, seizures in twelve patients (50%) and abnormal EEG in 15 patients (62.5%). Poor temperature regulation was found in 50% of patients and diabetes insipidus was documented in 3 patients (12.5%). The MRI showed complete or partial fusion of basal ganglia and thalami in 21 patients (87.5%) and 19 patients (79.2%) respectively, fused mesencephalon in 8 patients (33.3%), incomplete separation of mesencephalon from diencephalon in 4 patients (16.7%), dorsal cyst in 10 patients (41.7%), abnormal gyral pattern anteriorly in 15 patients (62.5%), anterior located sylvian fissures in 22 patients (99.7%), complete or partial agenesis of the corpus callosum (ACC) in all patients and Dandy-Walker malformation (DWM) in three patients (12.5%). A small occipital cephalocele was detected clinically and radiological as atretic type in MIH patient. Karyotype analysis demonstrated 47, XY+13 in a patient with alobar holoprosencephaly, 46, XY,t(12;13) (q13q24.1;q14q33) in a semilobar case associated with DWM, 46, XY, del(13)(q34) in one semilobar case and three cases had del 7q36 using FISH technique in two semilobar cases and one lobar case. Conclusion: This study highlights the clinical spectrum in patients with HPE and report a case of HPE and DWM associated with t(12;13). Neuroimaging delineated the pathogenesis underlying developmental defects in HPE. Accurate molecular diagnosis is crucial for further understanding of the pathogenesis of HPE.