Oligohydramnios Sequence Revisited in Relationship to Arthrogryposis, With Distinctive Skin Changes

Oligohydramnios sequence revisited in relationship to arthrogryposis, with distinctive skin changesJudith G. Hall* Departments of Medical Genetics, Pediatrics, University of British Columbia, BC Children’s Hospital Vancouver, British Columbia, Canada
Manuscript Received: 3 September 2013; Manuscript Accepted: 1 July 2014
How to Cite this Article: Hall JG. 2014. Oligohydramnios sequence
revisited in relationship to arthrogryposis,
with distinctive skin changes.
posis (1.2%) and were reviewed for clinical features and natural
history.Nonehadrenal agenesis or renaldisease.Twenty-twohad
a history of known rupture of membranes. Only 50% had pul-
monary hypoplasia at birth and only twodied (7%). Sixty percent
(18/30) seemed to have their multiple congenital contractures
(MCC) primarily on the basis of compression related to the
longstanding oligohydramnios and responded well to physical
therapy. On average they did not have intrauterine growth
restriction. “Potter” facies and remarkable skin changes were
present in all. An excess ofmales was observed in spite of the lack
of genitourinary anomalies. 2014 Wiley Periodicals, Inc.
Key words: arthrogryposis; multiple congenital contractures;
abnormal hair pattern; amniotic fluid leakage; attempted
termination of pregnancy; chorionic villus sampling (CVS)
compression; deformation; dimple; excess skin; large ears; male
excess; multiple congenital anomalies; oligohydramnios; Potter
syndrome; pulmonary hypoplasia; redundant skin; renal agenesis;
uterine anomaly; webbing
Conflict of interest: The author has no known conflicts of interest. Correspondence to:
Judith G. Hall, OC, MD, FRSC, FCAHS, Department of Pediatrics,
British Columbia’s Children’s Hospital, 4500 Oak Street, Room C234,
INTRODUCTION
Oligohydramnios (decreased amniotic fluid for gestational age)
was identified in the early 1900s by Pilgrim when it was observed
that it lead to changes in the placental surface (placenta nodosum)
[Blanc, 1961]. Renal agenesis was later recognized to be frequently
associated with oligohydramnios and multiple congenital contrac-
tures byBates [1933], and further expanded upon byPotter [Potter,
1946a,b]. This paper is a review of 30 cases of arthrogryposis
(multiple congenital contractures) all without renal agenesis, which
experienced longstanding oligohydramnios. The purpose of this
paper is to examine the relationship of oligohydramnios to arthrog-
ryposis (multiple congenital contractures) and the secondary and/
or tertiary effect on fetal skin.
Vancouver, BC, Canada, V6H 3N1.
E-mail: [email protected]
(wileyonlinelibrary.com): 26 August 2014
(multiple congenital contractures) have been collected by the
2014 Wiley Periodicals, Inc.
author over a 35-year period. These cases come from clinic visits
and consultations, as well as correspondence with physicians and
families. Thirty individuals with longstanding oligohydramnios
(average five months) were identified. Of these individuals, 20/
30 were personally examined in relation to their congenital con-
tractures and other clinical signs. These 30 affected individuals are
clearly a biased collection, not representative of the normal or
arthrogrypotic population; however, they are being reported in
order to raise awareness of their findings and present some inter-
esting questions that they raise. Family, pregnancy, and natural
histories were also reviewed. The records and photographs of the 30
individuals were examined, tabulated, and compared to the overall
group of cases with arthrogryposis (see Table I).
RESULTS WITH COMMENTARY
Demographics Both the time of year of birth and the parental age were not unusual
compared to the other cases of arthrogryposis. Regarding the length
of pregnancy: in one-third of these individuals, the births clustered
during the twoweeks before and after term. The one thirdwhowere
born before 36 weeks, were usually premature related to induction
2775
I. 3 0 Ca se s of
Ar th ro gr yp os is
W it h O lig oh yd ra m n io s
N o.
m n io s
or O lig o n ot ed
Co m pl ic at io ns
of Pr eg n an cy
W ee ks
at B ir th
Si ze
Co rd
Ag e M /F
Sk in
at B ir th
R O M
1 .4 kg
D ee p di m pl es
Ex te n de d
ar m s
of pr em
p os si bl e tw in
3 1
2 .4 kg
ha ir on
di st al
n or m al
Pn eu m ot ho ra x;
re qu ir ed
hy pe ra lim
H yp os pa di a;
cr yp to rc hi di sm
; di at he si s an d
hy po pl as ia of
ab do m in al
m us cl e
ch ro n ic
flu id
2 lb
1 oz
Ed em
fle xi on ;
hi p
Cr oa ky
vo ic e;
lim bs
m us cl e;
in gu in al
he rn ia s
ol ig o
4 AT P
AT P;
he rp es
1 .6 kg
D ee p di m pl es ;
ex tr a sk in ;
w eb s
fle xi on
de la y,
di st re ss
at bi rt h
- D ila te d
st en os is ;
tr is m us
ch ro n ic
ti ss u e;
le ak ag e
4 0
N R
sk in ; lo os e
jo in ts
fle xi on
pa lp eb ra l
fis su re ;
Co n n ec ti ve
ti ss ue ,
R O M ;
w it h
le ak ag e;
CV S;
1 .7
kg Am
ar ou n d
or at a;
fle xi on ;
ha n ds
n or m al
hy po pl as ia ;
th in
- U m bi lic al he rn ia ;
co rd
on le g
se co n da ry
to CV S
7 AT P
AT P;
2 .2 kg
D im pl es ;
fla tt en ed
fle xi on
pr ob le m
ec ho ge n ic
R eq ui re d G -t ub e;
tr is m us
ch ro n ic
B le ed in g 1 st
an d 2 n d ;
R O M
R ed un da n t
sk in
ar m s;
fle xe d
R et in op at hy
of pr em
m us cl e;
m ild
en la rg em
ol ig o
R O M
fe ta l
R ed un da n t
sk in ;
fle xi on ; Fx
os te op or -
Ch ro n ic
in su ff ic ie n cy
N ee de d G J tu be
fo r fe ed in g;
de cr ea se d
fa ci al
m ov em
"M SA FP ;
R O M
2 6
9 0 0 g
se pa ra ti on
M 2 4 /-
sk in ;
n da bl e;
fle xi on ;
hi p
re sp ir at or y
di st re ss
of pr em
he ar t m ur m ur ;
sa cr al di m pl e;
bi fid
ol ig o
AR Ts
3 8 .5
M CD A; 2
sk in ; de ep
di m pl es
fle xi on
de la y
G tu be ;
ol ig o
TA B LE
)
m n io s
or O lig o n ot ed
Co m pl ic at io n s
of Pr eg n an cy
W ee ks
at B ir th
Si ze
Co rd
Ag e M /F
Sk in
at B ir th
Fi br oi d;
tr au m a
AR Ts ;
Pa tc h of
un us ua l
de ep
fle xi on ;
pt os is ;
fa ci al
m ov em
ol ig o
m ov em
4 lb
9 oz
di m pl es ;
fle xi on
te th er ed
ol ig o
B ed re st ; R O M
3 4
4 lb
R si de fle
n ip pl es ;
di st re ss ;
en t
ol ig o
3 4
H ir su it ; th in
sk in ;
Fl ex ed
hi p;
ol ig o
Tw in
di ed
1 .0 kg
w eb bi n g;
de pi gm
en te d
fle xi on
hy po pl as ti c
n ip pl es
of pr em
in gu in al
he rn ia s;
m yo pi a
Se iz ur es
ol ig o; D Z
tw in
1 7
ol ig o
Tw o ha ir
w ho rl s;
di m pl es ;
m ot tl ed
sk in ; la rg e
ea rs
fle xi on ;
lo os e
de fo rm
sm al l ch es t
- H ig h pa la te ;
M al ro ta ti on
of gu t;
Po ss ib le
sy n dr om
ch ro n ic
sh or tl y
2 1
at 4 m o sk in
in fe ct io n
tr ea te d
n ec k
fle xi on ;
- H ig h pa la te
Pe n a- Sh ok ei r
ph en ot yp e;
di ed
lo ss
of am
3 8
de ep
G en er al iz ed
fle xi on
n ip pl es
; in gu in al
ol ig o
Fi b ro id ; se p ta te
ut er u s; b le ed
1 2 w ee ks ;
2 2 w ee ks
R O M ;
ch or io n it is
2 8
1 .2 kg
pl ac en ta ;
ba n d at
fu n du s
D ou bl e
re du n da n t
sk in
ar m s; fle xe d
le gs ;
hi ps ;
ve n ti la to r
ea rl y
m us cl e
; am
w it h
Tw in
lo st
m u lt ip le
p re vi ou s Ab
3 6
tu rn ed
fle xi on
of le gs ;
pr ea ur ic ul ar
ta g; ec to pi c
la cr im al
n ip pl e
ch ro n ic
Se pt at e ut er us ;
m al e tw in
lo ss ; 3 4 w k
R O M n ot ed ;
ol ig o
sc ar
Tw o ha ir
w ho rl s;
he m an g-
el bo w ;
de fe ct
of to es ;
up pe r
1 2 w ee ks
IU G R
lie
- G en er al iz ed
fle xi on ;
ro ck er
bo tt om
di st re ss ;
pr ob le m s
Se co n da ry
ef fe ct s
of ol ig o
)
m n io s
or O lig o n ot ed
Co m pl ic at io n s
of Pr eg n an cy
W ee ks
at B ir th
Si ze
Co rd
Ag e M /F
Sk in
at B ir th
2 0 w ee ks
2 pr ev io us
sp on ta n eo u s
ab or ti on s;
m ig ra in es
ea rl y
- M ild sc ol io si s;
ex te n de d
ar m s
m us cl e
w it h
ef fe ct s
of ol ig o
po st
es is
Po st
am n io
al re ad y
2 .8 kg
el bo w s;
n ec k
ur es
de fic it
n ee de d O 2
fa ci al m ov em
en t
re so lv ed ;
tr is m us ;
re qu ir ed
di sm
Ch ro n ic ol ig o
po st
2 2 w ee ks
- 3 6
5 lb
ar m s;
fle xe d
2 6 w ee ks
B ed re st
cr ea se s
re so lv ed ;
ok ay
fis su re s;
tr is m us
ef fe ct s
di ed
2 6 w ee ks
Cy st ic hy gr om
a n ot ed
N R
m us cl e
fle xi on ;
pe ct us ;
te th er ed
e se co nd ar y
to pu lm on ar y
hy po pl as ia
2 9
? 2 6 w ee ks
- 4 0
3 .2 kg
G en er al iz ed
fle xi on
O ka y
Ch ro n ic ol ig o
ef fe ct s
un kn ow
e
IU G R ; hy d ro n ep -
hr os is
1 .7 kg
ha ir lin e
D is ta l co n tr ac tu re s
D ev el op -
m en ta l
lo ss ;
hy dr on ep -
en la rg em
cr an io sy n os to si s
Sy n dr om
e w it h
ch ro n ic
ol ig o
N R , n o re po rt ; AT P, at te m pt ed
te rm
pr eg n an cy ; kg , ki lo gr am
; CP , ce re br al pa ls y; Fx , fr ac tu re .
2778 AMERICAN JOURNAL OF MEDICAL GENETICS PART A
HALL 2779
prolonged rupture of membranes.
Sex Ratio There is a trend toward an excess of males. A 2:1 ratio was observed
as compared to a normal sex ratio in the overall arthrogryposis
group. This is not statistically significant (Fisher exact test
P¼ 0.14); however, of interest because of the excess of males
observedwith renal agenesis, oligohydramnios, and arthrogryposis.
Multiple Births Three individuals reported that a twin had been lost earlier in the
pregnancy. One individual was one of dizygotic twins (the other
twin dying shortly after birth), and one individual was one of
dizygotic triplets (e.g., two of the triplets were monozygotic twins
and the affected twin who was part of the triplets was MZ mono-
chorionic diamniotic).
Survival Only two of these individuals were reported to have died shortly
after birth of pulmonary hypoplasia (one from pulmonary hypo-
plasia and prematurity, and the other with a complex of multiple
congenital anomalies). Three individuals had been attempted
terminations of pregnancy with continuing of the pregnancies
(previously reported in Hall [2012a]) and continual leakage of
fluid from the first trimester. One individual was an early chorionic
villus sampling (CVS) with subsequent leakage of fluid, one had
leakage after a second trimester amniocentesis, and two individuals
were born from bicornuate uteri (described as heart shaped with
short septums), but these two also had leakage from premature
rupture of membranes.
Family Histories Family histories were essentially negative: one family had a history
ofmultiple spontaneous abortions (this was not one of themothers
with bicornuate uterus). One family had a history of distant
relatives with clubfeet and two others had a relative who had
worn corrective shoes. One family had a pericentric inversion of
chromosome 9 (known to be a polymorphism) which the normal
mother transmitted to the affected son.
Deliveries Seventeen were delivered by Cesarean, of which nine were breech
presentation, one was in transverse lie, one was a twin pregnancy,
one was a triplet pregnancy, one was fetal distress, and in the other
four, the indication was not clear. There were eleven vaginal
deliveries, three of which were breech, and in the two other cases,
the delivery was not well described.
Maternal Health In four affected individuals, there had beenmaternal infertility and
fertility drugs were used for the present pregnancy in three indi-
viduals. Four mothers had illness during the pregnancy: two
gestational diabetes, one severe migraine, and one took seizure
medication during the pregnancy. Two other women had uterine
fibroids of significant size. Two mothers had septate uteri.
Timing of Decreased Amniotic Fluid Twenty-two of these affected individuals had history of rupture of
membranes (ROM) and chronic leakage of amniotic fluid. Oligo-
hydramnios began as early as eight weeks and often continued until
delivery. The average length of leakage from rupture of membranes
was 17.8 weeks. The least length of time for leakage of fluid was
reportedly as a few weeks; however, this was a pregnancy compli-
cated by a septate uterus fromwhich a twin had been lost previously
and the obvious ROM occurred at 34 weeks and the placenta was
implanted in a uterine scar with chorionic abruptio placentae.
Thus, more than 70% of these individuals historically had pro-
longed, chronic leakage and rupture of membranes. Pulmonary
hypoplasia was present in 15 (50%), and these required respiratory
support at birth and in one case for as long as six months. For the
other 50%, a small pocket of amniotic fluid (not recognized on
ultrasound studies), stress leading to early productionof surfactant,
or other unknown factors might be enabling pulmonary
maturation.
Birth Size Intrauterine growth restriction (IUGR) has been reported in the
past to be associated with longstanding oligohydramnios [Baines
and Scott, 1960; Kohler et al., 1970], however, birth size was in
general normal for gestational age in these individuals, although
there were more individuals below the 50th percentile for weight
than above. Length was about the 50th percentile and OFC was
about the 50th percentile (except on one syndromic microcephalic
child). This near normal weight at birth for gestational age could
relate to the presence of edema, since some affected individuals did
have pedal edema, in which case the edema resolved shortly after
birth. They did have excessively wrinkled skin; however, marked
edema or cystic hygroma in utero or after birth were not seen.
Placentas Placentas in general were not described. There was no information
available in 22 individuals. Of eight individuals with descriptions of
their placenta: two had placenta previa; one a circumvallate pla-
centa with decreased vascularization, a long cord, and amnion
nodosum; one had abruptio placenta with a normal cord; one
chronic abruption with attachment to a uterine scar; one case had a
marginal placenta; one had subchorionic separation; the triplet,
who was one of two monozygotic individuals among the triplets,
had a twovessel cord andmonochorionic, diamniotic placenta; and
one was said to be completely normal with a three vessel cord. Five
umbilical cords were noted to be long without comment on the
placenta while as noted above, one had a long cord with circum-
vallate placenta, giving 6/30 pregnancies with long umbilical cords
(a relatively large number compared to the overall group of
arthrogryposis). Notably, amnion nodosa was only identified in
FIG. 1. Note posteriorly placed hairline, dolicocephalic head shape, large ears, thin hair, and hypoplastic mid eyebrow, fullness around the
eyes, and the “tongue” of hair onto the forehead.
2780 AMERICAN JOURNAL OF MEDICAL GENETICS PART A
one case, suggesting some amniotic fluidmust have been present in
the third trimester, as the kidneys seem to have been functioning
normally. However, alternatively, normal fetal kidneys may make
some factor that lubricates intrauterine surfaces.
Craniofacial Features (see Table I) Although Potter described molding of the head and face with
frequent asymmetry, this was not a common feature in these
individuals with arthrogryposis and oligohydramnios without
renal anomalies. Instead, there was frequently a dolicocephalic
FIG. 2. Note eyes appear deep-set, hairline is posteriorly placed, and pro
head (probably associated with being in breech position for pro-
longed in utero periods), andprominent foreheadswith posteriorly
placed hairline, such that the hairline usually began aboutwhere the
earswereplaced (Figs. 1–3).Two individuals had striking “tongues”
of hair…