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TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands.

The combination of pulmonary agenesis/dysgenesis/hypoplasia, microphthalmia/anophthalmia, and a diaphragmatic defect (agenesis or eventration) is a rare syndrome presumed to have an autosomal recessive mode of inheritance based on a report of affected siblings born to unaffected parents [Seller et al., 1996]. The condition is known as Spear syndrome and Matthew-Wood syndrome, although genetic heterogeneity cannot be ruled out. We report on eight patients with this condition including a living child, three sibs and three isolated cases. Most presented with fetal ultrasound findings of microphthalmia/anophthalmia, and diaphragmatic eventration/hernia and in five, cardiac abnormalities were also found. The earliest detection was at 20 weeks gestation. This is the second report of sibs affected with this condition, which supports an autosomal recessive mode of inheritance. We present the first and only reported living patient with this condition and expand the intrafamilial, interfamilial, and ethnic variability of this condition. We suggest changing the condition's name to PDAC to reflect the most important components of this condition.

Limb malformations are frequent. These malformations are isolated or associated with anomalies of other developmental fields and accurate diagnostic is essential for prognosis evaluation, treatment and genetic counseling. Animal embryology and molecular biology techniques, have given us a better understanding of the processes of growth and patterning of the limb buds. The key genes that are involved in these processes have been identified and their interactions recognized. Human genetics has been able to identify, or at least localize, several genes implicated in limb development. We here review the present knowledge on these genes and their mutations responsible for limb anomalies.

Unlabelled: Dyggve-Melchior-Clausen syndrome (DMCS) is an autosomal recessive skeletal dysplasia. Clinical and radiological similarities with Morquio's syndrome can initially lead wrongly to this diagnosis., Case Report: A nine-year-old boy had mental retardation and progressive postnatal dwarfism. Platyspondyly and dysplastic epiphyses and metaphyses resembled those of Morquio's disease; however, clinical and radiological data led to the diagnosis of DMCS., Conclusion: Clinical and paraclinical features allowing the differentiation of Morquio's syndrome and DMCS are discussed. Initial clinical presentation may be similar, but the intellectual prognosis is different.