VACTERL

Congenital Abnormalities Terminology:

Single Congenital Abnormalities [1]
Term
Malformation
s
Deformations

Disruptions
Dysplasias

Definition
defects of organs or body parts due to an
intrinsically abnormal developmental
process. partially, abnormal, absent
formation
abnormalities of the position of body parts
due to extrinsic intrauterine mechanical
forces that modify a normally formed
structure
defects of organs or body parts that result
from destruction of or interference with
normal development
anomalies that result from the abnormal
organization of cells into tissues.

Example
HOXD3 mutations,
Retinoic acid
Clubfoot, congenital
dysplasia of the hip
Amniotic band
sequence
FGFR3
achondroplasia

Multiple Congenital Anomalies [1]

Term
Syndrome

Definition
pattern of anomalies that occur together and
are pathogenetically related
a pattern of anomalies in which a single
known defect in development causes a
cascade of subsequent abnormalities

Sequence

Developme
ntal field
defect
Associatio
n

pattern of anomalies caused by disturbance

of a region of the embryo that develops in a
contiguous physical space
two or more anomalies that are not
pathogenetically related and occur
together more frequently than expected by
chance

Example
Turner syndrome,
Cornelia de Lange
Potter syndrome
(oligohydraminos),
Prune-belly
sequence (urethral
malformations)
Holoprosencephaly,
Bladder exstrophy
VATER/VACTER

VACTERL:
-

Association of congenital abnormalities.

Diagnosis based on exclusion. 3 congential malformation

VATERassociationwasfirstnamedintheearly1970s.Changedto
VACTERL:Vascularanomalies,CardiacmalformationsandLimbanomalies
V = vertebral anomalies (60-80%)
A = anorectal malformation/ ARM (55-90%)
C = congenital cardiac defects (40-80%)

TE = trachea-esophageal anomalies (50-80%)

R = renal-urinary defects (50-80%)
L = limb defects (40-50%)
Background

1 in 10,000 -40,000 live births

More common in males
Causes: Multifactorial. No known underlying cause
Not associated with neurocognitive impairment
other associated problems [2]
o single umbilical artery
o duodenal atresia
o Meckel diverticulum
In a Cohort study of 107 patients, 11 adult patients were identified with
VACTERL [3]
o 25% of malformations were not identified during childhood.
40% of vertebral, 50% of cardiac, and 50% of renal
anomalies
o 50% of VACTERL diagnosis of VACTERL was not made until
adulthood
Patients may experience long-term sequelae that may not be evident
until adulthood or which are different in nature from the issues they
experienced in childhood.
o Thus uniform diagnostic work-up is advised in patients in whom
a diagnosis of VACTERL association is considered [3]

Treatment [4]
Surgical correction of the specific congenital anomalies (typically anal
atresia, certain types of cardiac malformations, and/or tracheoesophageal fistula) in the immediate postnatal period.
Monitor and manage for adult onset VACTERL
Prognosis [4] - Dependent on long-term medical management of sequelae
of the congenital malformations
Feature
Vertebral
anomalies
Anal atresia

Early potential
medical
complications
Scoliosis, tethered cord,
syrinx
Obstruction

Cardiac
malformation
s
Tracheoesophageal
fistula

Compromised
cardiopulmonary
function, dysrhythmias
Inability to feed,
respiratory compromise,
pneumonia

Late potential medical

complications
Progressive scoliosis, back pain,
osteoarthritis, tethered cord, syrinx
Incontinence, constipation, other
dysmotility, sexual dysfunction
Compromised cardiac function,
dysrhythmias
Gastro-esophageal reflux, increased
risk of gastro-esophageal cancers
(related to reflux), reactive airway
disease (differentiate from asthma

Renal
anomalies

Limb
abnormalities

Vesicoureteral reflux,
hydronephrosis, urinary
tract infections (also
related to anorectal
malformations)
Functional impairment

via PFT)
Urinary tract infections (also related
to anorectal malformations),
nephrolithiasis, Impaired renal
function
Functional impairment

Differential diagnosis [4]

Condition

Alagille
syndrome

Baller-Gerold
syndrome
CHARGE
syndrome

Currarino
syndrome
DiGeorge
syndrome

Features in
common with
VACTERL
association
Vertebral and
cardiac
anomalies; may
have renal
anomalies

Radial
anomalies, may
have anal
anomalies
Cardiac
malformations,
GU anomalies;
may also include
TEF

Sacral
malformations,
ARM
Cardiac
malformations,
renal anomalies,
other VACTERLtype anomalies

Features distinct
from VACTERL
association
Bile duct paucity and
cholestasis,
ophthalmologic
anomalies,
neurological
anomalies,
characteristic facial
appearance
Craniosynostosis, skin
anomalies
Colobomata, choanal
atresia,
neurocognitive and
growth impairment,
ear anomalies, cranial
nerve dysfunction,
characteristic facial
features
Presacral mass
Hypocalcemia, palatal
anomalies, learning
difficulties, immune
dysfunction,
neuropsychiatric
disturbances,
characteristic facial
features

Causes
Heterozygous
mutations in JAG1,
NOTCH2

Heterozygous
mutations
In RECQL4
Heterozygous
mutations in CHD7

Heterozygous
mutations/ deletions
of HLXB9
Deletion of one copy
of chromosome
22q11.2

Fanconia
anemia

Feingold
syndrome

Fryns
syndrome

Holt-Oram
syndrome
Mllerian
duct aplasia,
renal
aplasia, and
cervicothoracic
somite
dysplasia
Oculoauriculovertebral
syndrome

Opitz G/BBB
syndrome

Pallister-Hall
syndrome

All features of
VACTERL may
occur; radial
anomalies are
considered key
feature
GI atresia,
cardiac defects,
renal anomalies

GI
malformations,
cardiac defects,
GU anomalies
Cardiac
malformations,
limb
malformations
Vertebral
anomalies, renal
anomalies, GU
anomalies and
ARM; may also
have cardiac
and limb
anomalies
Vertebral
anomalies,
cardiac
abnormalities,
limb
abnormalities,
urogenital
anomalies
Anal anomalies,
heart defects,
TEF,
hypospadias
Imperforate
anus, renal
anomalies, limb
anomalies
(postaxial
polydactyly

Hematologic
anomalies,
pigmentation
anomalies
Brachymesophalangy,
toe syndactyly,
microcephaly,
cognitive impairment,
characteristic facial
appearance
Diaphragmatic
defects,
Neurocognitive
impairment,
characteristic facial
appearance
Cardiac conduction
disease (also reported
in VACTERL
association)
Syndactyly and
hearing loss have been
described

Recessive or X-linked
mutations in
multiple genes;
typically detected by
chromosomal
breakage studies
Heterozygous
mutations
In MYCN

No wellcharacterized
unifying causes

Heterozygous
mutations
In TBX5
Unknown; likely
heterogeneous

Ear anomalies
(microtia), hemifacial
microsomia,
neurocognitive
impairment, facial
clefts

Unknown; likely
heterogeneous

Hypertelorism,
syndactyly

X-linked form:
heterozygous/
hemizygous
mutations in MID1;
AD form: deletion
22q11.2
Heterozygous
mutations
In GLI3

Hypothalamic
hamartoma, bifid
epiglottis (ranging to
more severe types of
clefts), nail hypoplasia

TownesBrocks
syndrome

VACTERL-H

should serve as
a clue for the
PallisterHall syndrome)
Imperforate
anus, thumb
anomalies, renal
anomalies,
cardiac
anomalies
All core
component
features

Dysplastic ears,
hearing loss

Heterozygous
mutations
In SALL1

Hydrocephalus

Heterozygous
mutations
In PTEN,
heterozygous/hemiz
ygous mutations in
ZIC3; X-linked and
recessive forms have
been described

References
1. www.uptodate.com+approach-to-congenital-malformations?
source=search_result&search=approach+to+congenital+malformation&sele
ctedTitle=1~150
2. Solomon BD, Baker LA, Bear KA, et al. An approach to the identification of
anomalies and etiologies in neonates with identified or suspected VACTERL
(vertebral defects, anal atresia, tracheo-esophageal fistula with esophageal
atresia, cardiac anomalies, renal anomalies, and limb anomalies) association.
J Pediatr. 2014 Mar;164(3):451-7.e1
3. Long-term outcomes of adults with features of VACTERL association. Manu
S. Raam, Daniel E. Pineda-Alvarez, Donald W. Hadley, Benjamin D. Solomon
Eur J Med Genet. 2011 JanFeb; 54(1): 3441.
4. Solomon BD. VACTERL/VATER Association. Orphanet J Rare Dis. 2011 Aug
16;6:56