VACTERL with hydrocephalus and branchial arch defects: Prenatal, clinical, and autopsy findings in two brothers

Froster, Ursula G.; Wallner, Stephanie; Reusche, E.; Schwinger, E.; Rehder, Helga

doi:10.1002/(sici)1096-8628(19960315)62:2<169::aid-ajmg10>3.0.co;2-m

Cited by 29 publications

(17 citation statements)

References 8 publications

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“…Moreover, increased sister chromatid exchange and increased chromosome breakage in response to alkylating agents have been reported in this phenotype, further substantiating a possible link with Fanconi anaemia and, indeed, mutation of the FAC gene has been observed in affected twins 1114 18 However, the complex aetiology of the VATER-hydrocephalus phenotype is signalled by reports consistent with X linked inheritance18 and by variations in the phenotype reported, which have included abnormal ears, branchial arch defects, aqueduct stenosis, pancreatic hypoplasia, and abnormal lung lobulation 1617 19 Savarirayan et al ,20 in describing a case of Baller-Gerold syndrome, emphasise the potential for diagnostic error in making a diagnosis of Baller-Gerold syndrome or VACTERL association in children with this spectrum of anomalies without first excluding conditions such as Fanconi anaemia and Roberts syndrome, for which diagnostic tests are available.…”

supporting

confidence: 60%

“…Similarly, reports of affected sibs with the VATER-hydrocephalus phenotype15 16 and parental consanguinity in the parents of three affected males17support a likely autosomal recessive single gene aetiology in at least a proportion of cases with this phenotype. Moreover, increased sister chromatid exchange and increased chromosome breakage in response to alkylating agents have been reported in this phenotype, further substantiating a possible link with Fanconi anaemia and, indeed, mutation of the FAC gene has been observed in affected twins 11…”

mentioning

confidence: 91%

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A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association

Reardon

2001

Journal of Medical Genetics

106

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Mutations of the PTEN gene are associated with hamartoma-neoplasia syndromes. While germline mutations at this chromosome 10q22-23 locus have been observed in patients with Cowden syndrome (CS) and Bannayan-RileyRuvalcaba syndrome (BRR), both of which phenotypes are associated with hamartomata and neoplasia, somatic mutation of PTEN has been established in a wide variety of sporadically occurring neoplasia. CS and BRR share some clinical features, specifically hamartomata and lipomatosis. Investigation of other clinically distinct syndromes associated with lipomatosis and overgrowth has established germline and germline mosaic PTEN mutations in several patients with Proteus syndrome. To this expanding array of clinically distinct phenotypes associated with PTEN mutations, we now report a novel heterozygous germline mutation, H61D, in a patient with features of VATER association with macrocephaly and ventriculomegaly. (J Med Genet 2001;38:820-823)

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supporting

confidence: 60%

mentioning

confidence: 91%

A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association

Reardon

2001

Journal of Medical Genetics

106

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“…VACTERL‐H is a heterogeneous phenotype that can arise as a consequence of mutations in autosomal recessive FA genes and possibly other loci [Froster et al, 1996; Cox et al, 1997; Grech et al, 2000]. Two additional X‐linked pedigrees with affected males in two generations have been described [Genuardi et al, 1993; Lomas et al, 1998].…”

Section: Discussionmentioning

confidence: 99%

X‐linked VACTERL with hydrocephalus syndrome: Further delineation of the phenotype caused by FANCB mutations

McCauley

Masand

McGowan

et al. 2011

American J of Med Genetics Pt A

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X-linked VACTERL-hydrocephalus syndrome (X-linked VACTERL-H) is a rare disorder caused by mutations in the gene FANCB which underlies Fanconi Anemia (FA) complementation group B. Cells from affected males have increased chromosome breakage on exposure to DNA cross-linking agents. Only five FANCB mutations found in six affected males, including an affected uncle and nephew, have been reported. We have identified FANCB mutations in a further four affected families. The VACTERL-H phenotype segregates as an X-linked recessive trait in three of these. Each mutation is predicted to truncate the FANCB open reading frame and results in highly skewed X-inactivation in unaffected carrier females. Phenotypic data were available on six affected males. Comparison of the clinical findings in our patients with published clinical data (total 12 patients) shows that ventriculomegaly, bilateral absent thumbs and radii, vertebral defects, renal agenesis, and growth retardation are the major phenotypic signs in affected males. Less frequent are brain, pituitary, ear and eye malformations, gastrointestinal atresias (esophageal, duodenal and anal), tracheoesophageal fistula, lung segmentation defects, and small genitalia. Three of six of our patients survived the perinatal period. One boy lived up to 2 years 10 months but developed aplastic anemia and died of renal failure. These data show that loss-of-function FANCB mutations result in a recognizable, multiple malformation phenotype in hemizygous males for which we propose clinical criteria to aid diagnosis.

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“…It has a prevalence of 0.4–1.8% in the general population [Klin et al, 1996; Taylor et al, 1996; Janssen et al, 2000]. Until now, reported syndromic associations of vascular ring have included Down syndrome [Goldstein, 1965; Lo et al, 1989; Chaoui et al, 2005], Ullrich–Turner syndrome [Ho et al, 2004], 22q11 deletion [Momma et al, 1999; McElhinney et al, 2001a,b; Rauch et al, 2004; Park et al, 2007], as well as single patients reported for each of X‐linked VACTERL with hydrocephalus (MIM 314390) [Froster et al, 1996], a branchial cleft syndrome [Legius et al, 1990], MIDAS (microphthalmia, dermal aplasia, sclerocornea) syndrome (MIM 309801) [Happle et al, 1993] and Plummer–Vinson syndrome [Prokopenko, 1988].…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf–Hirschhorn syndrome

Müller

Kunath

et al. 2007

American J of Med Genetics Pt A

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Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS.

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VACTERL with hydrocephalus and branchial arch defects: Prenatal, clinical, and autopsy findings in two brothers

Cited by 29 publications

References 8 publications

A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association

A novel germline mutation of the PTEN gene in a patient with macrocephaly, ventricular dilatation, and features of VATER association

X‐linked VACTERL with hydrocephalus syndrome: Further delineation of the phenotype caused by FANCB mutations

Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf–Hirschhorn syndrome

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