A Bohring

Ali Al Kaissi

AM Slavotinek

B Duhamel

BR Versiani

Franz Grill

G Currarino

HJ Lin

J Blumel

JP Welch

Klaus Klaushofer

KS Kuehl

LJ Perrot

M-L Martinez-Frias

N Highmore

NN Finer

PK Duraiswami

SA Lynch

SL Rusnak

Y Fukada

English

PubMed

Springer - Publisher Connector

BioMed CentralCases Journal
ssOpen AcceCase Report
Caudal regression syndrome and popliteal webbing in connection 
with maternal diabetes mellitus: a case report and literature review
Ali Al Kaissi*1, Klaus Klaushofer1 and Franz Grill2
Address: 1Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 4th Medical Department, 
Hanusch Hospital, Vienna, Austria and 2Orthopaedic Hospital of Speising, Paediatric Department, Vienna, Austria
Email: Ali Al Kaissi* - ali.alkaissi@osteologie.at; Klaus Klaushofer - klaus.klaushofer@osteologie.at; Franz Grill - franz.grill@oss.at
* Corresponding author    
Abstract
Introduction: Most cases of caudal regression are sporadic or associated with gestational/
maternal diabetes. The condition is thought to be part of a spectrum including imperforate anus,
sacral agenesis and sirenomelia. Infants of diabetic mothers have two to three times the average
incidence of congenital anomalies.
Case Presentation: We report on a 7-year-old boy from non-consanguineous family in Austria
was born with features of caudal regression syndrome. A constellation of malformation complex
such as caudal regression syndrome and anorectal malformation complex were evident at birth. Of
great interest was the abnormal articulation between the pelvis and the remaining abnormal spine.
Spinal-pelvic instability, dislocation of the hip, and knee-flexion contracture associated with
popliteal webbing were the major orthopaedic abnormalities.
Conclusion: We showed that an offspring of a diabetic mother was at significant risk of developing
caudal regression syndrome. Our present patient demonstrated type1 of Welch and Aterman
classification. There was total sacral agenesis associated with subtotal lumbar agenesis. The lowest
vertebrae were resting above an iliac amphiathrosis. We strongly encourage primary care
providers to discuss the consequences of maternal diabetes mellitus as part of routine anticipatory
guidance for antenatal/prenatal management. Careful diabetic control in the preconceptional
period and the first eight weeks of pregnancy may lower the chances of congenital anomalies.
Introduction
Caudal regression syndrome and caudal dysgenesis syn-
drome are broad terms that refer to a heterogenous con-
stellation of congenital caudal anomalies affecting the
caudal spine and spinal cord, the hindgut, the urogenital
system, and the lower limbs. About 15–25% of mothers
of children with caudal regression syndrome have insulin-
dependant diabetes mellitus [1]. Welch and Aterman [2]
classified congenital sacral anomalies into 4 distinct clin-
ical types. (1) A non-familial type associated with mater-
nal diabetes mellitus showing complete absence of the
sacrum and lower vertebrae with multiple congenital
anomalies, (2) agenesis of the distal sacral or coccygeal
segments, (3) hemisacral dysgenesis with presacral ter-
atoma, and (4) hemisacral dysgenesis with anterior
meningocele. Autosomal dominant inheritance was sug-
gested for the last three types. Patients with caudal regres-
sion syndrome lack motor function below the level of the
remaining normal spine, similar to those with myelom-
eningocele. In myelomeningocele, however, sensory
Published: 19 December 2008
Cases Journal 2008, 1:407 doi:10.1186/1757-1626-1-407
Received: 22 October 2008
Accepted: 19 December 2008
This article is available from: http://www.casesjournal.com/content/1/1/407
© 2008 Al Kaissi et al; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 4
(page number not for citation purposes)
Cases Journal 2008, 1:407 http://www.casesjournal.com/content/1/1/407nerve function is impaired below the level of the affected
vertebrae. In caudal regression syndrome, sensation tends
to be present at much more caudal levels. Infants of dia-
betic mothers have two to three times the average inci-
dence of congenital anomalies.
Case Presentation
The boy was referred to the orthopaedic department at the
age of 3 years (fig 1). A loop colostomy in the left upper
quadrant was performed at birth for his imperforate anus.
He was the offspring of non-consanguineous parents.
Family history revealed a non-insulin diabetic mother.
There was no other history of significance. At birth he had
lower limb anomaly and imperforate anus. There was a
history of urine incontinence. Spinal-pelvic instability,
dislocation of the hip, and knee-flexion contracture asso-
ciated with popliteal webbing were the prominent ortho-
paedic abnormalities. Clinically he showed no
dysmorphic craniofacial features and he was of normal
intelligence. Hearing and vision were normal. No associ-
ated upper limb abnormalities. There was total sacral
agenesis and partial lumbar spinal agenesis. His left hip
was flexed and partially abducted because of a ptyrigium.
Equinovarus deformity of the left foot was present as well.
His motor development was normal over the right lower
limb but paralyses and loss of sensations over the left
lower limb was evident. He was able to move by means of
his normal motor right lower limb. Radiographic docu-
mentation showed total agenesis of the sacrum with sub-
total lumbar agenesis. The lowest lumbar vertebrae were
resting above an iliac amphiathrosis (fig 2). Lateral lower
limb radiograph showed fixed deformity of the left knee
associated with soft tissue web behind the knee extends
more than halfway down the tibia to the ankle associated
with oligodactyly associated with significant dysplasia of
the tarsal bones, agenesis and hypoplasia of the metatar-
sals and agenesis of the fourth metatarsophalangeal and
proximal phalanx (fig 3). For his left hip ptyrigium, cor-
rection has been done by the plastic surgeon, followed by
open reduction of the left hip, faced with the fixed flexion
contracture of the left knee. Elected amputation (subtro-
chanteric amputation) and prosthetic fitting might be our
choice. The advantage of subtrochanteric amputation over
amputation at a more distal level is the ease of prosthetic
fitting without having to deal with flexed femurs due to
hip flexion contracture.
Discussion
Caudal regression syndrome was first proposed by
Duhamel [3], based on his observation that sirenoid
monsters have a number of abnormalities in addition to
the characteristic synmelia or fusion of the lower limbs.
He further described an anchipod type of sirenoid mon-
ster in which the lower limbs are flexed and externally
rotated but remain independent. Rumplessness, a condi-
Fixed flexion deformity of the knee overwhelmed by exten-siv  popliteal webbingigure 1
Fixed flexion deformity of the knee overwhelmed by 
extensive popliteal webbing.
Anteroposterior pelvis radiograph showed total agenesis of the sacrum w th subtotal lumb r agenesisFigu e 2
Anteroposterior pelvis radiograph showed total 
agenesis of the sacrum with subtotal lumbar agene-
sis. The lowest lumbar vertebrae were resting above an iliac 
amphiarthrosis.Page 2 of 4
(page number not for citation purposes)
Cases Journal 2008, 1:407 http://www.casesjournal.com/content/1/1/407tion similar to sacral agenesis, has been noted in animals,
particularly chickens [4]. Duraiswami [5] demonstrated
that insulin injected into chick embryos could cause rum-
plessness. In 1959, Blumel et al, [6] first called attention
to the increased incidence of diabetes in mothers of
affected children, they observed that children with sacral
agenesis have been born to mothers who had abnormal
glucose tolerance tests but were not taking insulin. Rusnak
and Driscoll [7] reviewed the cases of 1150 infants born
to diabetic mothers. Three had sacral agenesis, making the
incidence 1 out of every 350 births to diabetic mothers.
Although it is tempting to attribute sacral agenesis to alter-
ations in carbohydrate metabolism induced by diabetes
or exogenous insulin injections. Welch and Aterman [2]
postulated that sacral agenesis resulted when an embryo
with a genetic predisposition to the condition was
exposed to some factor in the diabetic uterus. This
unknown stimulus could be insulin, antibodies to insu-
lin, or some other abnormality of carbohydrate metabo-
lism. Several children have been described in which a
sacral defect is inherited and there is no association with
maternal diabetes. They further described three forms of
familial sacral agenesis; familial hemisacrum type I
(Cohn-Bay-Nielson syndrome), familial hemisacrum type
II (Ashcraft syndrome), and familial partial sacral agene-
sis. A few instances of caudal regression have been
reported in siblings [8]. Chromosomal studies have been
normal [9], with few exceptions. A wide spectrum of spi-
nal and extra-spinal abnormalities in connection with
caudal regression syndrome has been reported. Bohring et
al., [10] reported 15 infants with agenesis of the lower ver-
tebral column overlapping with axial mesodermal dyspla-
sia and infants seen where the mother has diabetes.
Versiani et al., [11] report on 2 infants with absent lower
limbs. Both mothers had gestational diabetes. Currarino
syndrome [12], described a similar disorder caused by
mutation in the HLXB9 gene on chromosome 7q36. Also
called the ASP association, the A stands for anal stenosis,
ectopia or an imperforate anus. The S stands for either a
crescentic bony defect or malsegmentation of the sacrum
and the P a presacral mass, either an anterior menin-
gocele, or a teratoma or cyst. A part from caudal regression
syndrome, there seems to be an increase incidence of
other malformation complex such as visceral anomalies
in connection with maternal diabetes. Slavotinek et al.,
[13] reported three babies with situs ambiguous born to
mothers with insulin-dependent diabetes mellitus. One
had situs inversus with a neural tube defect and the other
two asplenia or polysplenia. Kuehl and Loffredo [14]
present evidence suggesting that situs abnormalities are
significantly more common in offspring of diabetic moth-
ers. Lin et al., [15] note the association between abnor-
malities of situs, features of oculo-auriculo-vertebral
complex, and maternal diabetes. Martinez-Frias [16] pre-
sented data suggesting that the incidence of transposition
of the great vessels and transposition of viscera was signif-
icantly increased in the offspring of diabetic mothers.
Conclusion
It has been known that diabetes-antedating pregnancy can
have severe adverse effects on fetal and neonatal out-
comes. As early as in the 1940s, it was recognized that
women who developed diabetes years after pregnancy had
experienced abnormally high fetal and neonatal mortal-
ity. The basic pathognomonic features in our current
patient were total sacral and partial lumbar spine agenesis
in connection with maternal diabetes mellitus. Prenatal
diagnosis by ultrasound is possible at 22 weeks of gesta-
tion, seen as sudden interruption of the spine due to
absence of vertebrae and a frog-like position of the lower
limbs. In a recent case report, CRS was diagnosed antena-
tally after detection of a large nuchal translucency,
although the diagnosis was not confirmed until 16 weeks
[17]
Abbreviations
CRS: Caudal regression syndrome; HLXB9 gene: home-
obox gene.
Consent
Written informed consent was obtained from the parents
for the purpose of publication of the manuscript and fig-
Lateral lower limb radiograph showed fixed deformity of the lef  knee associated w th soft tissue web behind the knee ex nds more than halfway down the ti ia to the an le asso-ciated with oligodacty y a sociated with significant dyspl ia of he tarsal bones, gene is and hypoplasia f the metatar-s ls a d agen sis of h  fourt m tatarsophalang al and prox-imal ph lanxFigur  3
Lateral lower limb radiograph showed fixed deform-
ity of the left knee associated with soft tissue web 
behind the knee extends more than halfway down 
the tibia to the ankle associated with oligodactyly 
associated with significant dysplasia of the tarsal 
bones, agenesis and hypoplasia of the metatarsals 
and agenesis of the fourth metatarsophalangeal and 
proximal phalanx.Page 3 of 4
(page number not for citation purposes)
Cases Journal 2008, 1:407 http://www.casesjournal.com/content/1/1/407Publish with BioMed Central   and  every 
scientist can read your work free of charge
"BioMed Central will be the most significant development for 
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central 
yours — you keep the copyright
Submit your manuscript here:
http://www.biomedcentral.com/info/publishing_adv.asp
BioMedcentral
ures of their child. A copy of the written consent is availa-
ble for review by the editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
All of the authors were involved in the clinico-radio-
graphic assessment and finalising the paper. All authors
have red and approved the final version of the paper.
Acknowledgements
We wish to thank the parents for their remarkable cooperation.
References
1. Lynch SA, Wang Y, Strachan T, Burn J, Lindsay S: Autosomal dom-
inant sacral agenesis: Currarino syndrome.  J Med Genet 2000,
37:561-566.
2. Welch JP, Aterman K: The syndrome of caudal dysplasia: a
review, including etiologic considerations and evidence of
heterogeneity.  Pediat Path 1984, 2:313-327.
3. Duhamel B: From the mermaid to anal imperforation: the syn-
drome of caudal regression.  Arch Dis Child 1961, 36:152-155.
4. Highmore N: The history of generation.  London: J. Martin;
1650:31. 
5. Duraiswami PK: From the mermaid to anal imperforation.
The syndrome of caudal regression.  Arch Dis Child 1961,
36:152-155.
6. Blumel J, Evans EB, Eggers GWN: Partial and complete agenesis
or malformation of the sacrum with associated anomalies.  J
Bone Joint Surg Am 1959, 41A(3):497-518.
7. Rusnak SL, Driscoll SG: Congenital spine anomalies in infants of
diabetic mothers.  Pediatrics 1965, 35:989-995.
8. Finer NN, Bowen P, Dunbar LG: Caudal regression anomalad
(sacral agenesis) in siblings.  Clin Genet 1978, 13:353-358.
9. Perrot LJ, Williamson S, Jimenez JF: The caudal regression syn-
drome in infants of diabetic mothers.  Ann Clin Lab Sci 1987,
17:211-220.
10. Bohring A, Lewin SO, Reynolds JF, Voigtländer T, Rittinger O, Carey
JC, Köpernik M, Smith R, Zackai EH, Leonard NJ, Gritter HL, Bam-
forth JS, Okun N, McLeod DR, Super M, Powell P, Mundlos S, Hen-
nekam RCM, van Langen IM, Viskochil DH, et al: Polytopic
anomalies with agenesis of the lower vertebral column.  Am J
Med Genet 1999, 87:99-114.
11. Versiani BR, Gilbert-Barnes E, Giuliani LR, et al: Caudal dysplasia
sequence: severe phenotype presenting in offspring of
patients with gestational and pregestational diabetes.  Clin
Dysmorphol 2004, 13:1-5.
12. Currarino G, Coln D, Votteler T: Triad of anorectal, sacral, and
presacral anomalies.  Am J Roentgenol 1981, 137(2):395-398.
13. Slavotinek AM, Hellen E, Gould S, Coghill SB, Huson SM, Hurst JA:
Three infants of diabetic mothers with malformations of left-
right asymmetry – further evidence for the aetiological role
of diabetes in this malformation spectrum.  Clin Dysmorphol
1996, 5:241-247.
14. Kuehl KS, Loffredo C: Risk factors for heart disease associated
with abnormal sidedness.  Teratology 2002, 66(5):242-248.
15. Lin HJ, Owens TR, Sinow RM, Fu PC, Devito A, Beall MH, Lachman
RS: Anomalous inferior and superior venae cavae with oculo-
auriculovertebral defect: review of Goldenhar complex and
malformations of left-right asymmetry.  Am J Med Genet 1998,
75:88-94.
16. Martinez-Frias M-L, Bermejo E, Rodriguez-Pinilla E, Prieto L, Frias JL:
Epidemiological analysis of outcomes of pregnancy in gesta-
tional diabetic mothers.  Am J Med Genet 1998, 78:140-145.
17. Fukada Y, Yasumizu T, Tsurugi Y, Ohta S, Hoshi K: Caudal regres-
sion syndrome detected in a fetus with increased nuchal
translucency.  Acta Obstet Gynecol Scand 1999, 78:655-656.Page 4 of 4
(page number not for citation purposes)


Caudal regression syndrome and popliteal webbing in connection with maternal diabetes mellitus: a case report and literature review

Crossref

al: Polytopic anomalies with agenesis of the lower vertebral column.

Aterman K: The syndrome of caudal dysplasia: a review, including etiologic considerations and evidence of heterogeneity. Pediat Path

Caudal dysplasia sequence: severe phenotype presenting in offspring of patients with gestational and pregestational diabetes. Clin Dysmorphol

Driscoll SG: Congenital spine anomalies in infants of diabetic mothers. Pediatrics

From the mermaid to anal imperforation: the syndrome of caudal regression. Arch Dis Child

From the mermaid to anal imperforation. The syndrome of caudal regression. Arch Dis Child

GWN: Partial and complete agenesis or malformation of the sacrum with associated anomalies.

Hoshi K: Caudal regression syndrome detected in a fetus with increased nuchal translucency. Acta Obstet Gynecol Scand

JA: Three infants of diabetic mothers with malformations of leftright asymmetry – further evidence for the aetiological role of diabetes in this malformation spectrum. Clin Dysmorphol

JF: The caudal regression syndrome in infants of diabetic mothers. Ann Clin Lab Sci

JL: Epidemiological analysis of outcomes of pregnancy in gestational diabetic mothers.

Lachman RS: Anomalous inferior and superior venae cavae with oculoauriculovertebral defect: review of Goldenhar complex and malformations of left-right asymmetry.

LG: Caudal regression anomalad (sacral agenesis) in siblings. Clin Genet

Loffredo C: Risk factors for heart disease associated with abnormal sidedness. Teratology

S: Autosomal dominant sacral agenesis: Currarino syndrome.

The history of generation.

Votteler T: Triad of anorectal, sacral, and presacral anomalies.

file:///data/remote/core/dit/data/Springer-OA/pdf/190/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvMTc1Ny0xNjI2LTEtNDA3LnBkZg==.pdf

Caudal regression syndrome and popliteal webbing in connection with maternal diabetes mellitus: a case report and literature review

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

Crossref

Springer - Publisher Connector