Olfactory bulb and olfactory tract abnormalities in acrocallosal syndrome and Greig cephalopolysyndactyly syndrome.

We describe association of olfactory bulb and olfactory tract abnormalities in a child with acrocallosal syndrome caused by kinesin family membrane 7 (KIF7) mutation in sonic hedgehog pathway. The child also had fontanellar bone in the anterior fontanelle, short sagittal suture, sagittal synostosis, hippocampal malrotation and Joubert malformation. Fontanellar bone has been described in GLI3 mutation and mutant mice models but has not been reported in KIF7 mutation. We briefly review the role of sonic hedgehog pathway and its components KIF7 and GLI3 in forebrain and olfactory system development and also describe olfactory system abnormality in a child with GLI3 mutation.

Corpus callosum agenesis, severe mental retardation, epilepsy, and dyskinetic quadriparesis due to a novel mutation in the homeodomain of ARX.

We report on a patient with agenesis of the corpus callosum (ACC), severe mental retardation, infantile spasms and subsequent intractable epilepsy, spastic/dyskinetic quadriparesis, severe limb contractures, and scoliosis. This complex, newly described phenotype, is due to a novel non-conservative missense mutation in the ARX homeodomain (c.1072A>T; p.R358W), inherited from the unaffected mother. Differently from previously reported non-conservative mutations falling within the same domain, p.R358W did not cause XLAG. It is therefore possible that differences in clinical manifestations between our patient and those with XLAG, are related to the different position of the amino acid substitution in the homeodomain, or to the different chemical properties introduced by the substitution itself. To test the hypothesis that the patient's mother was asymptomatic because of non-random X chromosome inactivation (XCI), we performed DNA methylation studies of the human androgen receptor gene, demonstrating skewing of the XCI ratio (85:15). The complex phenotype described here combines different traits that had previously been linked to various ARX mutations, including conservative missense mutations in the homeodomain and expansion in the first ARX polyalanine tract and contributes to the expanding pleiotropy associated with ARX mutations.

Prevalence and timing of pregnancy termination for brain malformations.

OBJECTIVE: To determine the prevalence and the timing of pregnancy termination relative to the type of central nervous system (CNS) malformations. Design Retrospective cohort study. SETTING: Multidisciplinary centre for prenatal diagnosis in the Languedoc-Roussillon region, France. POPULATION: A cohort of 481 pregnancy terminations performed between 2005 and 2009. METHODS: Detailed post-termination fetal and neuropathological analyses were carried out to identify the CNS malformations. Then, the prevalence and timing of pregnancy termination were assessed relative to the identified malformations. RESULTS: About one-third of pregnancy terminations (143/481) were performed for severe CNS malformations. Up to 24 weeks of gestation (WG), pregnancy terminations (56.6%) were carried out mainly for defects occurring during the two major first steps of CNS development (neurulation and differentiation of cerebral vesicles). After 24 WG, pregnancy terminations (43.3%) were mainly performed for corpus callosum agenesis (16/17), vermian agenesis (10/12) and gyral anomalies (13/15). For hindbrain malformations and gyral anomalies, there was a significant relationship between the timing of pregnancy termination and the presence of a severe ventriculomegaly at prenatal diagnosis (p=0.002 and p=0.02, respectively). CONCLUSION: By classifying CNS malformations according to the neuropathological analysis, the authors show that the timing and prevalence of pregnancy termination are distributed in a manner that is consistent with what is currently known on the development of brain. They are also influenced by the French prenatal screening policy and the variable expressivity of the brain malformations and associated lesions.

The role of ultrasonography in the diagnosis of fetal isolated complete agenesis of the corpus callosum: a long-term prospective study.

OBJECTIVE: To evaluate the role of a dedicated neurosonographer in prenatal diagnosis of isolated complete agenesis of the corpus callosum (iCACC) and to asses the postnatal outcome of these infants. METHODS: Prospective study between January 2004 to December 2004 at Fetal Maternal Medical Centre 'Artemisia', Rome, Italy. A detailed ultrasound scan was performed in fetuses affected by iCACC by a dedicated fetal neurosonographer (CG). In all cases, magnetic resonance imaging (MRI) within 5 weeks and 13-15 months after birth was performed. A comparison was made between prenatal findings following the ultrasound scan and postnatal MRI. In these cases, a follow-up of 4-years was performed with a neurological evaluation. RESULTS: Among 23 cases of ACC diagnosed at our centre in the study period, CACC was diagnosed in 17 fetuses. Two were then excluded due to associated malformations, one was lost at follow-up and one patient opted to terminate her pregnancy. Newborn MRI confirmed the ultrasonographic diagnosis of iCACC in all 13 cases. A regular development was present in 92.3% of prenatally diagnosed iCACC. CONCLUSION: A dedicated neurosonographer could diagnose the iCACC with the same accuracy as MRI and in up to 90% of cases the newborn will have a regular development.

Benefits of examination by post mortem performed magnetic resonance imaging of foetus: haemorrhage in germinal matrix.

Post mortem magnetic resonance imaging is demonstrated as a supplementary method to classic pathological-anatomical autopsy in determining anomalies of the foetus. Frequently it plays a key role; primarily where the possibilities of performing autopsy are somehow limited (autolysis, ventricular dilatation). Specification of the final diagnosis subsequently enables us to improve prenatal diagnostics, both by means of magnetic resonance imaging and primarily by correlation with the prenatal ultrasound scan; this feedback improves the later method. This case report demonstrated that post mortem magnetic resonance imaging, in contrast with prenatal ultrasound examination, showed extensive haemorrhage in the germinal matrix, and also illustrated indirect symptoms testifying to agenesis of the corpus callosum. Prenatal ultrasound examination showed only hydrocephalus and absence of septum pellucidum. Pathological-anatomical autopsy of the brain was insufficient with regard to advanced autolysis and brain haemorrhage.

Aicardi syndrome mimicking intrauterine hydrocephalus.

Congenital enlargement of the cerebral ventricles is now commonly recognized in utero due to the availability of high resolution prenatal ultrasonography. It is important to distinguish between congenital hydrocephalus and ventricular enlargement due to malformations, infections or other destructive processes because these disorders can have markedly different prognoses. We report an infant diagnosed with Aicardi syndrome in the newborn period based on brain MRI and ophthalmological findings after she was referred for evaluation of hydrocephalus seen on fetal ultrasound. Aicardi syndrome most commonly comes to medical attention because of seizures later in infancy.

Prenatal and postnatal follow-up of a fetal interhemispheric arachnoid cyst with partial corpus callosum agenesis, asymmetric ventriculomegaly and localized polymicrogyria. Case report.

We report a case of a fetal interhemispheric arachnoid cyst associated with partial callosal agenesis and asymmetric ventriculomegaly. After second trimester ultrasound diagnosis and evaluation, magnetic resonance imaging (MRI) at 28 weeks showed polymicrogyria laterally to the cyst. The parents decided to continue the pregnancy. The diagnosis was confirmed after birth by transfontanellar ultrasound examination and MRI. In the neonatal period, the child was sleepy and showed axial hypotonia. At 1 month of age, he had a normal neurological examination. Cyst-peritoneal shunting was performed at 5 weeks of age because the cyst increased markedly in size, and shunt revision was required at 8 months of age. At 17 months, he had mild left-side hemiparesis but he could walk alone and had begun to speak. To date, the child never experienced seizures. We review other published cases and discuss the postnatal outcome of this rare association.