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Cite this page: Hill, M.A. (2021, April 17) Embryology VACTERL. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:VACTERL
Birth Defects Res. 2019 Mar 18. doi: 10.1002/bdr2.1493. [Epub ahead of print] HSPA6: A new autosomal recessive candidate gene for the VATER/VACTERL malformation spectrum. Kause F1, Zhang R1,2, Ludwig M3, Schmiedeke E4, Rissmann A5, Thiele H6, Altmueller J6,7, Herms S2,8,9, Hilger AC1,10, Hildebrandt F11, Reutter H1,12. Author information Abstract BACKGROUND: The VATER/VACTERL association refers to the nonrandom co-occurrence of at least three of the following component features (CFs): vertebral defects (V), anorectal malformations (ARM) (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). Patients presenting with two CFs have been termed VATER/VACTERL-like phenotypes.
METHODS: We surveyed the exome for recessive disease variants in three affected sib-pairs. Sib-pair 971 consisted of two brothers with ARM and additional hydronephrosis in one brother. Sib-pair 1098 consisted of two sisters with ARM. In family 1346, the daughter presented with ARM and additional hypoplasia of both small fingers and ankyloses. Her brother presented with unilateral isolated radial hypoplasia. Sib-pairs 971 and 1346 resembled a VATER/VACTERL-like phenotype.
RESULTS: We detected a novel maternally inherited missense variant (c.1340G > T) and a rare paternally inherited deletion of the trans-allele in HSPA6 in both siblings of family 1346. HSPA6 belongs to the heat shock protein (HSP) 70 family. Re-sequencing of HSPA6 in 167 patients with VATER/VACTERL and VATER/VACTERL-like phenotypes did not reveal any additional bi-allelic variants.
CONCLUSIONS: Until now, only TNF-receptor associated protein 1 (TRAP1) had been reported as an autosomal recessive disease-gene for the VATER/VACTERL association. TRAP1 belongs to the heat shock protein 90 family (HSP90). Both Hsp70 and Hsp90 genes have been shown to be important embryonic drivers in the formation of mouse embryonic forelimb tissue. Our results suggest HSPA6 as a new candidate gene in VATER/VACTERL-like phenotypes.
© 2019 Wiley Periodicals, Inc.
KEYWORDS: HSPA6; VATER/VACTERL association; anorectal malformations; autosomal recessive inheritance; whole-exome sequencing PMID: 30887706 DOI: 10.1002/bdr2.1493
A rare case of laryngeal cleft in association with VACTERL and malrotation
Radiol Case Rep. 2018 Dec 6;14(3):315-319. doi: 10.1016/j.radcr.2018.11.002. eCollection 2019 Mar.
Jesse C1, Jonathan S1, Jeremy N1, June K1. Author information Abstract We report a rare case of a neonatal girl who presented with coughing and dyspnea immediately after feeds. At birth, she was noted to have an imperforate anus with a posterior fourchette fistula from which she was stooling. Initial imaging with radiography showed a normal bowel gas pattern; however, lumbar vertebral anomalies were noted. An upper GI series was performed and revealed a laryngeal cleft and malrotation. Ultrasound confirmed malrotation with an abnormal SMA-SMV relationship. Since laryngeal cleft is a rare condition and may not be known to most radiologists, its incidence is likely underestimated. It is important to note the association of laryngeal clefts with VACTERL and malrotation. In addition, it is essential not to confuse a laryngeal cleft with a tracheoesophageal fistula since the management differs.
KEYWORDS: Laryngeal cleft; Laryngotracheoesophageal cleft; Malrotation; VACTERL PMID: 30546815 PMCID: PMC6287062 DOI: 10.1016/j.radcr.2018.11.002
Orphanet J Rare Dis. 2011 Aug 16;6:56. doi: 10.1186/1750-1172-6-56.
VACTERL/VATER association is typically defined by the presence of at least three of the following congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities. In addition to these core component features, patients may also have other congenital anomalies. Although diagnostic criteria vary, the incidence is estimated at approximately 1 in 10,000 to 1 in 40,000 live-born infants. The condition is ascertained clinically by the presence of the above-mentioned malformations; importantly, there should be no clinical or laboratory-based evidence for the presence of one of the many similar conditions, as the differential diagnosis is relatively large. This differential diagnosis includes (but is not limited to) Baller-Gerold syndrome, CHARGE syndrome, Currarino syndrome, deletion 22q11.2 syndrome, Fanconi anemia, Feingold syndrome, Fryns syndrome, MURCS association, oculo-auriculo-vertebral syndrome, Opitz G/BBB syndrome, Pallister-Hall syndrome, Townes-Brocks syndrome, and VACTERL with hydrocephalus. Though there are hints regarding causation, the aetiology has been identified only in a small fraction of patients to date, likely due to factors such as a high degree of clinical and causal heterogeneity, the largely sporadic nature of the disorder, and the presence of many similar conditions. New genetic research methods offer promise that the causes of VACTERL association will be better defined in the relatively near future. Antenatal diagnosis can be challenging, as certain component features can be difficult to ascertain prior to birth. The management of patients with VACTERL/VATER association typically centers around surgical correction of the specific congenital anomalies (typically anal atresia, certain types of cardiac malformations, and/or tracheo-esophageal fistula) in the immediate postnatal period, followed by long-term medical management of sequelae of the congenital malformations. If optimal surgical correction is achievable, the prognosis can be relatively positive, though some patients will continue to be affected by their congenital malformations throughout life. Importantly, patients with VACTERL association do not tend to have neurocognitive impairment.
PMID: 21846383 PMCID: PMC3169446 DOI: 10.1186/1750-1172-6-56
|Vertebral anomalies||X-ray; ultrasound and/or MRI of the spine||X-ray may not show subtle spinal anomalies, and will be unable to detect associated anomalies such as tethered cord or syrinx|
|Anal atresia||Physical examination/observation, abdominal ultrasound for genitourinary anomalies||Additional testing is typically required to define anatomy, especially if concomitant genitourinary anomalies are present|
|Cardiac malformations||Echocardiogram||Other, more precise techniques, such as cardiac CT or MRI may be helpful to further detail anomalies|
|Tracheo-esophageal fistula||Physical examination/observation (contrast studies are rarely required)||Patients with VACTERL association but without true TEF may still present with swallowing/breathing anomalies, and clinicians should have a low index of suspicion for confirmatory radiological testing|
|Renal anomalies||Renal ultrasound||Further testing, such as a voiding cystouerethrogram, may be required in the presence of renal anomalies or if there is other evidence of issues such as vesicoureteral reflux|
|Limb anomalies||Physical examination, X-ray||Important not to overlook, as the presence of limb anomalies often prompts testing for Fanconi anemia|
|Suggested testing for patients (in addition to a careful physical examination by an experienced clinician) suspected to have VACTERL association. Specific modalities used should be dictated by the risk-benefit ratio for the specific situation.|
|Table reference  Links: VACTERL | vertebra | heart | renal | limb|