Oesophageal atresia with tracheoesophageal fistula and anal atresia in a patient with a de novo microduplication in 17q12

Tracheoesophageal Fistula (TOF) is a congenital anomaly for which the cause is unknown in the majority of patients. OA/TOF is a variable feature in many (often mono-) genetic syndromes. Research using animal models targeting genes involved in candidate pathways often result in tracheoesophageal phenotypes. However, there is limited overlap in the genes implicated by animal models and those found in OA/TOF-related syndromic anomalies. Knowledge on affected pathways in animal models is accumulating, but our understanding on these pathways in patients lags behind. If an affected pathway is associated with both animals and patients, the mechanisms linking the genetic mutation, affected cell types or cellular defect, and the phenotype are often not well understood. The locus heterogeneity and the uncertainty of the exact heritability of OA/TOF results in a relative low diagnostic yield. OA/TOF is a sporadic finding with a low familial recurrence rate. As parents are usually unaffected, de novo dominant mutations seems to be a plausible explanation. The survival rates of patients born with OA/TOF have increased substantially and these patients start families; thus, the detection and a proper interpretation of these dominant inherited pathogenic variants are of great importance for these patients and for our understanding of OA/TOF aetiology.

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Not all neonates with oesophageal atresia and tracheoesophageal fistula are a surgical emergency

Journal of Pediatric Surgery ◽

10.1016/j.jpedsurg.2018.10.074 ◽

2019 ◽

Vol 54 (2) ◽

pp. 244-246

Author(s):

Andrea Thompson ◽

Hemanshoo Thakkar ◽

Hammad Khan ◽

Iain E. Yardley

Keyword(s):

Tracheoesophageal Fistula ◽

Oesophageal Atresia ◽

Surgical Emergency

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Mandibulofacial dysostosis with microcephaly: a syndrome to remember

BMJ Case Reports ◽

10.1136/bcr-2019-229831 ◽

2019 ◽

Vol 12 (8) ◽

pp. e229831 ◽

Cited By ~ 2

Author(s):

Joana Brandão Silva ◽

Diana Soares ◽

Miguel Leão ◽

Helena Santos

Keyword(s):

Congenital Malformations ◽

Tracheoesophageal Fistula ◽

Oesophageal Atresia ◽

Cerebral Atrophy ◽

Rare Condition ◽

Pathogenic Mutation ◽

Heterozygous Carrier ◽

Short Neck ◽

Lower Lip ◽

Mandibulofacial Dysostosis

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare condition that causes abnormalities of the head and face. Other major extracranial malformations may also be found. The authors present a case of an MFDM in a 35 weeks newborn with antenatal growth restriction. The patient required resuscitation at birth and was diagnosed with oesophageal atresia with tracheoesophageal fistula at day 1. At physical examination he presented multiple congenital malformations including prominent forehead, plagiocephaly, low-set ears, malformed auricles, hypertelorism, downward-slanting eyes, micrognathia, everted lower lip, short neck, wide-spaced nipples and inguinal hernia. Imaging investigation showed dysplasia of the inner ear with agenesis of the vestibular–cochlear nerves and global cerebral atrophy. Analysis of the EFTUD2 gene revealed that the patient was a heterozygous carrier of a pathogenic mutation (c.831_832del[p.Lys277Asnsf*7]), which has not been previously described. This case illustrates the challenges faced in diagnosing and treating MFDM patients.

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