Microcephaly, malformation of brain development and intracranial calcification in sibs: Pseudo‐TORCH or a new syndrome

• Published in: American journal of medical genetics. Part A 2008-11, Vol.146A (22), p.2929-2936
• Main Authors: Abdel‐Salam, Ghada M.H., Zaki, Maha S., Saleem, Sahar N., Gaber, Khaled R.
• Format: Article
• Language: English
• Subjects: abnormal gyral pattern; Abnormalities, Multiple - genetics; Abnormalities, Multiple - pathology; autosomal recessive inheritance; band‐like calcification; basal ganglia calcification; Biological and medical sciences; Brain - abnormalities; Brain - pathology; brain stem calcification; Calcinosis - genetics; Consanguinity; Diagnosis, Differential; dysplastic ventricles; Fatal Outcome; Female; fetal MRI; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant; Infant, Newborn; Male; Malformations of the nervous system; Medical genetics; Medical sciences; microcephaly; Microcephaly - genetics; Nervous system (semeiology, syndromes); Neurology; Pedigree; prenatal diagnosis; Siblings; Syndrome; uncontrolled seizures
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32549

We report on five sibs affected by congenital microcephaly, growth retardation, sloping forehead, bitemporal grooving and micrognathia. Generalized tonic‐clonic seizures started very early in life. Postnatal brain computerized tomography (CT) presented cortical band‐like calcification, calcification of basal ganglia and brain stem while brain magnetic resonance imaging (MRI) revealed abnormal gyral pattern, marked loss of white matter, dysplastic ventricles, polymicrogyria, hypogenesis of corpus callosum and cerebellar hypoplasia. No abnormalities of the internal organs, eye, or skeleton were found to be associated with this syndrome. Fetal Magnetic resonance imaging helped reaching the diagnosis in utero in one patient. Three patients died in the first years of life while the others within days after birth preceded by high fever and status epilepticus. These patients present many overlapping features with pseudo TORCH syndrome, however, the imaging findings are quite different. We propose that the distinct pattern in these sibs constitutes genetic disorder of microcephaly, developmental brain malformation and intracranial calcification of likely autosomal recessive inheritance. © 2008 Wiley‐Liss, Inc.