Clinical evaluation revealed that, in addition to bilateral eye defects, SOX2 mutations were associated with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, variable defects affecting the corpus callosum and mesial temporal structures, hypothalamic hamartoma, sensorineural hearing loss, and esophageal atresia.
A previously unreported case with severe bilateral microphthalmia and oesophageal atresia has a de novo missense mutation, R74P, that alters a highly evolutionarily conserved residue within the high mobility group domain, which is critical for DNA-binding of SOX2.
Duplications and polyalanine expansions within the transcription factor SOX3 have recently been described in association with infundibular hypoplasia, hypopituitarism and variable mental retardation, whilst mutations in SOX2 are associated with variable hypopituitarism in association with learning difficulties, oesophageal atresia and anophthalmia.
Second study on the recurrence risk of isolated esophageal atresia with or without trachea-esophageal fistula among first-degree relatives: no evidence for increased risk of recurrence of EA/TEF or for malformations of the VATER/VACTERL association spectrum.
Shared clinical features in this group of patients include microcephaly, prenatal onset growth restriction, heart defects, tracheoesophageal fistula, and esophageal atresia (TEF/EA), skeletal anomalies, and moderate to severe global developmental delay.
Recently, the EFTUD2 gene was identified in patients with mandibulofacial dysostosis associated with microcephaly, intellectual disability and esophageal atresia.
Phenotype analysis of Polish patients with mandibulofacial dysostosis type Guion-Almeida associated with esophageal atresia and choanal atresia caused by EFTUD2 gene mutations.
Whole exome sequencing identifies a mutation in EYA1 and GLI3 in a patient with branchio‑otic syndrome and esophageal atresia: Coincidence or a digenic mode of inheritance?
Haploinsufficiency of NOG gene has been implicated in the development of conductive hearing loss, skeletal anomalies including symphalangism, contractures of joints, and hyperopia in our patient and may also contribute to the development of tracheo-esophageal fistula and/or esophageal atresia.
Results suggest that the GSTM1(-/-) null genotype may play an important role in the development of EA during early embryogenesis as a consequence of altered detoxification processes both in children and in the mothers.
In this study, we analyzed the sequence variants of coding regions for a set of esophageal atresia-related genes including MYCN, SOX2, CHD7, GLI3, FGFR2 and PTEN for mutations using PCR-based target enrichment and next-generation sequencing in 27 patients with esophageal atresia.
We propose to consider a role for selected genes such as AATF (cell proliferation and apoptosis) and TADA2L (Wnt pathway) at the 17q12 region as well as developmental and transcriptional pathways represented by these genes, in the development of OA/TOF and VATER association.
Loss of proprotein convertase subtilisin/kexin type 5 (Pcsk5) results in multiple developmental anomalies including cardiac malformations, caudal regression, pre-sacral mass, renal agenesis, anteroposterior patterning defects, and tracheo-oesophageal and anorectal malformations, and is a model for VACTERL/caudal regression/Currarino syndromes (VACTERL association - Vertebral anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula and/or Esophageal atresia, Renal & Radial anomalies and Limb defects).