Abdel-Salam et al. (2008) reported on a family in which five siblings were affected with a disorder characterized by congenital microcephaly, growth retardation, sloping forehead, bitemporal grooving, and micrognathia. The patients had an early-onset of tonic-clonic seizures. Brain imaging studies revealed cortical band-like calcification, calcification of basal ganglia and brain stem, abnormal gyral pattern, marked loss of white matter, dysplastic ventricles, polymicrogyria, corpus callosum hypogenesis, and cerebellar hypoplasia. Although the clinical features overlapped with that seen in TORCH syndrome, Abdel-Salam et al. (2008) noted that the imaging results were quite different. Three of the siblings died within the first year of their lives, and the two others within days of their birth. In the case of one patient, fetal MRI was able to prenatally detect the condition. Abdel-Salam et al. (2008) suggested that this was likely a genetic disorder of autosomal recessive inheritance. The next year, Abdel-Salam and Zaki (2009) described another family with two brothers affected with this same disease. The parents were healthy and consanguineous, while the boys had the typical features of congenital microcephaly that became more pronounced postnataly, refractory seizures, band-like intracranial calcification, polymicrogyria, dysplastic ventricles, and loss of white matter. The proband in this family was included in a study of six families (two of them Arab, including the Egyptian family) undertaken by O'Driscoll et al. (2010) to understand the genetic basis of BCLPMG. Autozygosity mapping and copy number analysis enabled O'Driscoll et al. (2010) to identify intragenic deletions and mutations in the OCLN gene in all studied families. The Egyptian family was found to have an intragenic deletion of exon 3, and also possibly exon 4, predicted to result in removal of some or all of a highly conserved domain in the protein.

[See also: Saudi Arabia > O'Driscoll et al., 2010].

Al-Dabbous et al. (1998) described a Kuwaiti Bedouin family with a rare autosomal recessive infection-like syndrome of microcephaly, intracranial calcification, and CNS disease. The proband was a female who presented with congenital microbrachycephaly, hypertonia, early onset tonic-clonic seizures, a palpable liver, and mild pulmonary stenosis. She had a delay in attaining her developmental milestones. CT brain revealed partial agenesis of the corpus callosum, atrophy, dilated ventricles, and scattered calcific foci in the caudate nuclei, thalami, and the periventricular white matter. Immunnological studies were negative for TORCH infection. Three of her cousins were also affected, and presented with spasticity. CT brain in their cases also showed microcephaly with intracranial calcification.

O'Driscoll et al. (2010) studied six families with BCLPMG, including a Saudi Arabian consanguineous family with at least one affected child. The proband in the Saudi family was a female who presented at birth with hypotonia and hyperreflexia had her first seizure at 6-weeks of age. She tested negative for congenital infection at birth. Brain imaging revealed bilateral symmetrical polymicrogyria in a perisylvian and temporal distribution with severe loss of cerebral volume, simplified gyration, and wide sylvian fissures. The study also showed bilateral calcification in the deep cortical gray matter, and variable calcification in the pons, thalami, and globus pallidus. Molecular analysis enabled the identification of a homozygous splice site change in the 5-6 intron (c.1037+5G>A) of the Occludin gene in the proband.