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Subject: TheFetus.net - Pterygium syndrome, multiple lethal -Vincenzo Suma, MD, Alberto Marini, MD, Francesco Bellitti, PhD, Guglielmo Serpotta, MD, Riccardo Sai
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      <FONT size=3D4>
      <P class=3DMsoNormal=20
      style=3D"mso-margin-top-alt: auto; mso-margin-bottom-alt: =
auto"><SPAN=20
      style=3D"FONT-SIZE: 10pt; FONT-FAMILY: Arial"><FONT=20
      size=3D2>199</FONT></FONT><FONT size=3D2>4-01-11-13 Pterygium =
syndrome,=20
      multiple lethal =A9 Suma <A=20
      =
href=3D"http://www.thefetus.net/">http://www.thefetus.net/</A></FONT></SP=
AN><FONT=20
      size=3D4><FONT face=3DArial size=3D2><SPAN=20
      style=3D"FONT-SIZE: 10pt; mso-bidi-font-size: 12.0pt">=20
      </SPAN></FONT><B><SPAN style=3D"FONT-FAMILY: " Arial Unicode=20
      MS??><O:P></O:P></SPAN></P>
      <DIV class=3DMsoNormal style=3D"TEXT-ALIGN: center" =
align=3Dcenter><FONT=20
      face=3DArial size=3D3><SPAN style=3D"FONT-SIZE: 12pt">
      <HR align=3Dcenter width=3D"100%" SIZE=3D2>
      </SPAN></FONT></DIV>
      <P><FONT face=3DArial>Pterygium syndrome, multiple=20
      lethal</FONT></B></FONT><B></P>
      <P align=3Djustify><FONT face=3DArial>Vincenzo Suma, MD, Alberto =
Marini, MD,=20
      Francesco Bellitti, PhD, Guglielmo Serpotta, MD, Riccardo=20
      Saia,MD</FONT></P></B><FONT size=3D2>
      <P align=3Djustify><FONT face=3DArial>Address correspondence to: =
<B>Vincenzo=20
      Suma, MD</B>,Ultrasonic Service, Division of Obstetrics and =
Gynecology,=20
      Civilian Hospital, via Giustinioni 3, 35128 Padua, Italy. Ph:=20
      39-49-8213481 Fax: 39-49-8213493.</FONT></FONT><B></P></B>
      <P align=3Djustify><FONT size=3D2><FONT =
face=3DArial><B>Synonyms:</B>=20
      None.</FONT></FONT></P>
      <P align=3Djustify><FONT size=3D2><FONT =
face=3DArial><B>Definition:</B> A=20
      syndrome characterized by multiple pterygia (chinto-sternum, =
cervical,=20
      axillary, antecubital, popliteal and crural), flexion =
contractures,=20
      skeletal abnormalities, hypoplastic heart and lungs, facial =
anomalies and=20
      cystic hygroma<SUP>1,2</SUP>.</FONT></FONT></P><FONT size=3D2>
      <P align=3Djustify><FONT face=3DArial><B>Prevalence</B>: Unknown; =
fewer than=20
      200 cases reported.</FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>Etiology:</B> Probably =
related to an=20
      autosomal recessive inheritance<SUP>3</SUP>, but an X-linked =
recessive=20
      inheritance is also advanced<SUP>4</SUP>.</FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>Pathogenesis:</B> The =
data suggest=20
      that the syndrome combines the manifestations of a jugular =
lymphatic=20
      obstruction sequence with those of an early severe fetal akinesia =
sequence=20
      with two possible mechanisms: an abnormally fragile collagen =
constitution=20
      or an early fetal muscular "dystrophy"</FONT></P>
      <P align=3Djustify><FONT face=3DArial>Associated anomalies: =
Multiple pterygia,=20
      cystic hygroma, hypoplastic lungs and heart, skeletal =
abnormalities,=20
      facial anomalies, and growth retardation (Table 3).</FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>Differential =
diagnosis:</B> With a=20
      normal karyotype: lethal popliteal pterygium syndrome =
(Bartsocas-Papas=20
      syndrome), and Pena-Shokeir syndrome</FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>Prognosis:</B> =
Lethal.</FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>Recurrence risk</B>: 25% =
in the=20
      autosomal recessive syndrome.</FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>Management: </B>Pregnancy =
termination=20
      before viability. Standard obstetrical management after=20
      viability.</FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>CODES =3D MESH =
</B>Pterygium=20
      congenital, contracture congenital<B> BDE </B>2274<B> MIM =
</B>253290,=20
      265000, 312150<B> ICD9 </B>228.1<B> CDC</B> 228.100=20
      </FONT></P></FONT><B><I>
      <P align=3Djustify></I><FONT=20
      face=3DArial><BIG>Introduction</BIG><I></P></I></FONT></B><FONT =
face=3DArial=20
      size=3D2>
      <P align=3Djustify>The multiple pterygium syndrome is a rare =
autosomal=20
      recessive disorder characterized by multiple pterygia (chin to =
sternum,=20
      cervical, axillary popliteal, crural, antecubital), flexion =
contractures,=20
      hypoplastic heart and lungs, skeletal abnormalities, facial =
anomalies=20
      (hypertelorism, epicanthic folds, flattened nose, micrognathia, =
and=20
      apparently low-set ears), and cystic hygroma. Two types have been=20
      described: a lethal form involving abortions and stillbirths and a =
non-=20
      lethal form appearing in children and adolescents.</P></FONT>
      <P align=3Djustify><BIG><FONT face=3DArial>Case<B>=20
      </B>report</FONT></BIG></P><FONT size=3D2>
      <P align=3Djustify><FONT face=3DArial>A 30-year-old G woman was =
referred at 11=20
      weeks of gestation for ultrasound evaluation. Her past obstetrical =
history=20
      was remarkable in that both her first and second pregnancies had =
been=20
      interrupted at 15 and 18 weeks, respectively, because of fetal =
spina=20
      bifida and myelomeningocele. At the time, pre- and post-conception =

      treatment with folic acid was advised in view of future =
pregnancies. Her=20
      third and fourth pregnancies resulted in the birth of two healthy =
babies=20
      with no anomalies.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>Since the current pregnancy =
was=20
      unplanned, the patient had not undergone preventive treatment with =
folic=20
      acid. Ultrasound examination with transabdominal and transvaginal =
probes=20
      revealed a single fetus, compatible with age, with a small cystic =
mass on=20
      the back of the neck (fig. 1,2). The diagnosis of cystic hygroma =
was=20
      formulated. Subsequent CVS showed a normal 46XX =
karyotype.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>A repeat sonographic scan at =
15=20
      gestational weeks (fig. 3) evidenced the disappearance of the =
cystic=20
      hygroma and its substitution by fairly thick skin (pterygium). No =
fetal=20
      movements were observed.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>Further ultrasonic =
examinations at 18=20
      and 21 weeks showed the fetus in the same position. The upper and =
lower=20
      extremities were fixed, flexed and shortened. The feet were =
clubbed. The=20
      chest appeared narrow and deformed, and the vertebral column =
showed marked=20
      scoliosis of the cervico-thoracic region (fig. 4-7). The volume of =

      amniotic fluid was increased.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>After discussion with the =
couple, the=20
      pregnancy was terminated by prostaglandin perfusion.</FONT></P>
      <P align=3Djustify><FONT face=3DArial><IMG height=3D480=20
      =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image20.jpg"=20
      width=3D480></FONT></P><B>
      <P><FONT face=3DArial>Figura 1: </FONT></B><FONT =
face=3DArial>Cystic mass at=20
      the back of the head on a transverse view (11 weeks). </FONT></P>
      <P><FONT face=3DArial><IMG height=3D480=20
      =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image21.jpg"=20
      width=3D480> </FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>Figura 2: </B>Cystic mas =
at the back=20
      of the head on a longitudinal view (11 weeks). </FONT></P>
      <P align=3Djustify><FONT face=3DArial><IMG height=3D480=20
      =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image22.jpg"=20
      width=3D480></FONT></P><B>
      <P><FONT face=3DArial>Figura 3:</FONT></B><FONT face=3DArial> =
Pterygium colli=20
      (15 weeks). </FONT></P>
      <P align=3Djustify><FONT face=3DArial><IMG height=3D480=20
      =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image23.jpg"=20
      width=3D480></FONT></P><B>
      <P><FONT face=3DArial>Figura 4:</FONT></B><FONT face=3DArial> =
Longitudinal=20
      view of the chest and abdomen. The chest appears narrow and =
deformed (18=20
      weeks). </FONT></P>
      <P align=3Djustify><FONT face=3DArial><IMG height=3D480=20
      =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image24.jpg"=20
      width=3D480></FONT></P><B>
      <P><FONT face=3DArial>Figura 5:</FONT></B><FONT face=3DArial>Lower =
extremities=20
      showing talipes equino-varus (21 weeks) </FONT></P>
      <P align=3Djustify><FONT face=3DArial><IMG height=3D480=20
      =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image25.jpg"=20
      width=3D480></FONT></P><B>
      <P><FONT face=3DArial>Figura 6: </FONT></B><FONT =
face=3DArial>Upper=20
      extremities showing flexion of the wrists (21 weeks). </FONT></P>
      <P align=3Djustify><FONT face=3DArial><IMG height=3D480=20
      =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image26.jpg"=20
      width=3D480></FONT></P>
      <P align=3Djustify><FONT face=3DArial><B>Figura 7: </B><I>View of =
the hands=20
      showing camptodacty ly (21 weeks)</I></FONT></P></FONT>
      <P align=3Djustify><FONT face=3DArial>Post-mortem =
findings</FONT></P><FONT=20
      face=3DArial size=3D2>
      <P align=3Djustify>Physical examination of the child showed =
micrognathia, a=20
      small mouth<B>, </B>epicantal folds, and very short neck. Multiple =

      pterygia involved the neck, axillae, antecubital, popliteal, =
crural and=20
      interphalangeal areas<B>. </B>The chest was short. Both feet were =
clubbed,=20
      and the anus was a blind pouch (fig. 8). In addition, radiographic =
studies=20
      showed multiple pterygia but no bony fusion (fig. 9).</P></FONT>
      <TABLE width=3D"44%" border=3D1>
        <TBODY>
        <TR>
          <TD vAlign=3Dbottom width=3D"28%"><FONT face=3DArial =
size=3D2><IMG=20
            height=3D899=20
            =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image27.jpg"=20
            width=3D504></FONT></TD>
          <TD width=3D"72%"><FONT face=3DArial size=3D2><IMG =
height=3D944=20
            =
src=3D"http://www.thefetus.net/images/article-images/face_and_neck/pteryg=
ium%20syndrome_multiple%20lethal_files/image28.jpg"=20
            width=3D518></FONT></TD></TR>
        <TR>
          <TD width=3D"28%"><FONT size=3D2>
            <P align=3Djustify><FONT face=3DArial><B>Figure 8</B><I>: =
Post-mortem=20
            view showing micrognathia, hand and feet </I>deformities and =

            pterygia of joints.</FONT></FONT></P></TD>
          <TD width=3D"72%"><FONT size=3D2><FONT face=3DArial><B>Figura =
9:=20
            </B>Lateral X-ray showing no bony fusions and limb=20
            contractures.</FONT></FONT></TD></TR></TBODY></TABLE>
      <P align=3Djustify><FONT face=3DArial =
size=3D4><B>Discussion</B></FONT><FONT=20
      size=3D2></P></FONT>
      <P align=3Djustify><FONT face=3DArial>Prevalence</FONT></P><FONT =
face=3DArial=20
      size=3D2>
      <P align=3Djustify>The incidence and prevalence of this syndrome =
are=20
      unknown. Reliable statistics concerning these aspects are not =
available;=20
      fewer than 200 cases have been reported.</P></FONT>
      <P align=3Djustify><FONT face=3DArial>Etiology</FONT></P><FONT =
face=3DArial=20
      size=3D2>
      <P align=3Djustify>The syndrome is probably related to an =
autosomal=20
      recessive gene mutation. However, following the description of a =
family in=20
      which three male fetuses presenting a similar lethal multiple =
pterygium=20
      syndrome were born to mothers who were first cousins through the =
female=20
      line, an X-linked recessive inheritance was advanced. Therefore, =
in view=20
      of this possibility, all women with a family history of an =
affected male=20
      member should be monitored.</P></FONT>
      <P align=3Djustify><FONT face=3DArial>Pathogenesis</FONT></P><FONT =
size=3D2>
      <P align=3Djustify><FONT face=3DArial>According to Hale, the limb =
pterygia=20
      syndromes may be classified as autosomal dominant or recessive =
form; the=20
      latter include two lethal forms: the lethal popliteal pterygium =
syndrome=20
      (Bartsocas-Papas syndrome) and the lethal multiple pterygium =
syndrome=20
      (Table 1). Subsequently, Hale et al. proposed the subdivision of =
the=20
      lethal multiple pterygium syndrome into three groups based on the =
age of=20
      onset on intrauterine growth retardation, the degree of neck =
swelling, and=20
      the presence or absence of bony fusions of the vertebral and long=20
      bones.</FONT></P>
      <TABLE height=3D299 width=3D"77%" border=3D1>
        <TBODY>
        <TR>
          <TD width=3D"100%" colSpan=3D2 height=3D39><FONT =
face=3DArial><B>Table 1:=20
            </B><I>Type of syndromes:</I></FONT></TD></TR>
        <TR>
          <TD width=3D"45%" height=3D37>
            <UL>
              <LI><FONT size=3D3><FONT face=3DArial><B>Dominant</B>=20
              </FONT></FONT></LI></UL></TD>
          <TD width=3D"55%" height=3D37>
            <UL>
              <LI><FONT face=3DArial><FONT =
size=3D3><B>Recessive</B></FONT><BIG>=20
              </BIG></FONT></LI></UL></TD></TR>
        <TR>
          <TD vAlign=3Dtop width=3D"45%" height=3D175>
            <UL>
              <UL>
                <LI><FONT face=3DArial>Popliteal pterygium syndrome =
</FONT>
                <LI><FONT face=3DArial>Antecubital pterygium syndrome =
</FONT>
                <LI><FONT face=3DArial>Multiple pterygium syndrome + =
ptosis +=20
                skeletal abnormalities </FONT></LI></UL></UL></TD>
          <TD vAlign=3Dtop width=3D"55%" height=3D175>
            <UL>
              <UL>
                <LI><FONT face=3DArial>Multiple pterygium syndrome =
</FONT>
                <LI><FONT face=3DArial>Lethal multiple pterygium =
syndrome </FONT>
                <LI><FONT face=3DArial>Lethal popliteal pterygium =
syndrome=20
                (Bartsocas-Papas syndrome) + facial cleft </FONT>
                <LI><FONT face=3DArial>Popliteal pterygium syndrome + =
ectodermal=20
                dysplasia </FONT>
                <LI><FONT face=3DArial>Other conditions with limb =
pterygia </FONT>
                <LI><FONT face=3DArial>Kuskokwin syndrome </FONT>
                <LI><FONT face=3DArial>Mietens syndrome </FONT>
                <LI><FONT face=3DArial>Weyers syndrome </FONT>
                <LI><FONT face=3DArial>Roberts syndrome=20
        </FONT></LI></UL></UL></TD></TR></TBODY></TABLE>
      <P align=3Djustify><FONT face=3DArial>Several mechanisms have been =
advanced to=20
      explain the pathogenesis of limb pterygia, the most notable =
manifestation=20
      of the lethal multiple pterygium syndrome. According to Hartwig et =

      al<SUP>5</SUP>, an abnormally fragile collagen constituction is=20
      responsible for the lethal immobility, pterygia and many of the =
associated=20
      anomalies. Skin normally grows due to the stimuli exerted by the=20
      mechanical forces of the underlying tissues (i.e., bones) which =
grow=20
      outwardly, and thus follows the normal contour of the structure to =
which=20
      it is solidly attached.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>The first fetal movements, =
which start=20
      at about 8 weeks development, are abrupt and uncoordinated, and =
may cause=20
      muscle fiber lacerations if the reticular fiber collagen is =
particularly=20
      fragile. Consequently, muscular disuse, atrophy, and fetal =
immobility will=20
      follow if the fetus is immobile. Fixed flexion positions of the =
joints and=20
      weak connections between the skin and underlying structures may be =

      present. In this onset, the skin may grow along a shorter track =
than the=20
      structures to which it is attached. The decreased growth stimulus =
leads to=20
      the formation of multiple pterygia and a series of structural=20
      abnormalities (pulmonary hypoplasia, low-set ears, micrognathia, =
hand and=20
      foot deformities, abnormal bone modeling) known as the "fetal =
akinesia=20
      deformation sequence".</FONT></P>
      <P align=3Djustify><FONT face=3DArial>Following a histological =
study of the=20
      neuromuscular system of fetuses with the lethal multiple pterygium =

      syndrome, Moerman et al more recently advanced that this syndrome =
combines=20
      the manifestations of a jugular lymphatic obstruction sequence =
with those=20
      of an early severe fetal akinesia sequence. The jugular lymphatic=20
      obstruction causes edema and cystic hygroma colli. Lymph vessels =
and=20
      muscles are both mesodermal structures; an early, genetically =
determined=20
      biochemical insult affecting these structures may cause an arrest =
in the=20
      development of muscle (primary aplasia) whose fibers are replaced =
by=20
      adipose tissue. This early "muscular dystrophy" most likely =
underlies the=20
      fetal akinesia sequence as part of the lethal multiple pterygium=20
      syndrome.</FONT></P></FONT>
      <P align=3Djustify><FONT face=3DArial>Diagnosis</FONT></P><FONT =
size=3D2>
      <P align=3Djustify><FONT face=3DArial>The prenatal diagnosis of =
lethal=20
      multiple pterygium syndrome by means of ultrasonography is =
possible in the=20
      second trimester of gestation in most cases when there is a high =
index of=20
      suspicion due a previous occurrence<SUP>1,9,14</SUP>. However, =
normal=20
      ultrasound findings do not exclude the presence of an affected =
fetus, and=20
      since the syndrome may present an intrafamilial variability, =
fetoscopy may=20
      be needed. When the syndrome is instead sporadic, as in our case, =
the=20
      ultrasonographic findings that help formulate the diagnosis of =
lethal=20
      multiple pterygium syndrome from the 14-15 week of pregnancy are: =
1)=20
      cystic hygroma at the back of the head and neck; 2) non-immune =
fetal=20
      hydrops; 3) short and fixed limbs, 4) lack of fetal movements, and =
5)=20
      polyhydramnios.</FONT></P>
      <P align=3Djustify></FONT><FONT face=3DArial size=3D3>Differential =

      diagnosis</FONT><FONT size=3D2></P>
      <P align=3Djustify><FONT face=3DArial>In the presence of a normal =
karyotype,=20
      the differential diagnosis should include lethal popliteal =
pterygium=20
      syndrome (Bartsocas-Papas syndrome) and Pena-Shokeir syndrome =
(Table=20
      2).</FONT></P><I>
      <P align=3Djustify><FONT face=3DArial><B><FONT size=3D3>Table =
2:</FONT></B>=20
      Differential diagnosis of lethal multiple pterygium=20
      syndrome.</FONT></P></I></FONT>
      <TABLE width=3D"75%" border=3D1>
        <TBODY>
        <TR>
          <TD width=3D"17%"><B><FONT face=3DArial>Syndrome =
</FONT></B></TD>
          <TD width=3D"83%"><B><FONT =
face=3DArial>Differences</FONT></B></TD></TR>
        <TR>
          <TD width=3D"17%"><FONT face=3DArial size=3D2>Lethal =
popliteal</FONT></TD>
          <TD width=3D"83%"><FONT face=3DArial size=3D2>Pterygia only in =
the lower=20
            extremities.</FONT></TD></TR>
        <TR>
          <TD width=3D"17%"><FONT size=3D2><FONT face=3DArial>Pterygium =
<FONT=20
            size=3D1>7</FONT></FONT></FONT></TD>
          <TD width=3D"83%"><FONT size=3D2><FONT face=3DArial>Cleft lip =
and palate=20
            with pitted lower lip.Genital abnormalities ( bifid scrotum, =

            hypoplastic penis, cryptorchidism, hypoplastic labia )<FONT=20
            size=3D1>16.</FONT></FONT></FONT></TD></TR>
        <TR>
          <TD width=3D"17%"><FONT face=3DArial =
size=3D2>Pena-Shokeir,type I=20
          </FONT></TD>
          <TD width=3D"83%"><FONT face=3DArial size=3D2>Many =
similarities are=20
            present, but multiple pterygia are=20
absent.</FONT></TD></TR></TBODY></TABLE>
      <P align=3Djustify><FONT face=3DArial>Associated =
anomalies</FONT></P>
      <P align=3Djustify><I><FONT face=3DArial><FONT =
size=3D2><I><B>Table=20
      3:</B></I></FONT> Associated anomalies</FONT></I></P>
      <UL>
        <LI><FONT face=3DArial><FONT size=3D2>Cystic hygroma of the =
neck</FONT>=20
        </FONT>
        <LI><FONT face=3DArial><FONT size=3D2>Edema and hydrops</FONT> =
</FONT>
        <LI><FONT face=3DArial><FONT size=3D2>Multiple pterygia at all =
joints</FONT>=20
        </FONT>
        <UL>
          <LI><FONT face=3DArial><FONT size=3D2>chin-to-sternum</FONT>=20
        </FONT></LI></UL>
        <UL>
          <LI><FONT face=3DArial><FONT size=3D2>cervical</FONT> </FONT>
          <LI><FONT face=3DArial><FONT size=3D2>axillary</FONT> </FONT>
          <LI><FONT face=3DArial><FONT size=3D2>antecubital</FONT> =
</FONT>
          <LI><FONT face=3DArial><FONT size=3D2>popliteal</FONT> </FONT>
          <LI><FONT face=3DArial><FONT size=3D2>crural</FONT>=20
</FONT></LI></UL></LI></UL>
      <UL>
        <LI><FONT face=3DArial><FONT size=3D2>Muscular-skeletal =
anomalies</FONT>=20
        </FONT>
        <UL>
          <LI><FONT face=3DArial size=3D2>flexion contracture of =
multiple joints=20
          </FONT>
          <LI><FONT face=3DArial><FONT size=3D2>muscle atrophy/abdominal =
muscle=20
          hypoplasia</FONT> </FONT>
          <LI><FONT face=3DArial><FONT size=3D2>short stature</FONT> =
</FONT>
          <LI><FONT face=3DArial><FONT size=3D2>talipes as =
equinovarus</FONT>=20
</FONT>
          <LI><FONT face=3DArial size=3D2>bony fusions: humero-ulnar, =
radio-ulnar,=20
          between </FONT>
          <LI><FONT face=3DArial><FONT size=3D2>spine apophyses, between =
epiphyseal=20
          cartilage of the long bones.</FONT> =
</FONT></LI></UL></LI></UL>
      <UL>
        <LI><FONT face=3DArial><FONT size=3D2>Facial anomalies</FONT> =
</FONT>
        <UL>
          <LI><FONT face=3DArial><FONT size=3D2>hypertelorism</FONT> =
</FONT>
          <LI><FONT face=3DArial><FONT size=3D2>epicanthic folds</FONT>=20
        </FONT></LI></UL>
        <UL>
          <LI><FONT face=3DArial><FONT size=3D2>downward slanting =
palpebral=20
          fissures</FONT> </FONT>
          <LI><FONT face=3DArial><FONT size=3D2>flattened nasal =
bridge</FONT>=20
</FONT>
          <LI><FONT face=3DArial><FONT size=3D2>micrognathia</FONT> =
</FONT>
          <LI><FONT face=3DArial><FONT size=3D2>low set ears</FONT> =
</FONT>
          <LI><FONT face=3DArial><FONT size=3D2>cleft palate</FONT> =
</FONT>
          <LI><FONT face=3DArial><FONT size=3D2>cleft upper lip (non=20
          mid-line)</FONT> </FONT></LI></UL></LI></UL>
      <UL><FONT face=3DArial></FONT></UL>
      <UL>
        <LI><FONT face=3DArial><FONT size=3D2>Cardiac hypoplasia</FONT> =
</FONT>
        <LI><FONT face=3DArial><FONT size=3D2>Lung =
hypoplasia/agenesia</FONT>=20
</FONT>
        <LI><FONT face=3DArial><FONT size=3D2>Small chest</FONT> </FONT>
        <LI><FONT face=3DArial><FONT size=3D2>Congenital hernia of the=20
        diaphragm</FONT> </FONT>
        <LI><FONT face=3DArial><FONT size=3D2>External genital =
hypoplasia=20
        /cryptorchidism</FONT> </FONT>
        <LI><FONT face=3DArial><FONT =
size=3D2>Hydranencephaly/porencephaly</FONT>=20
        </FONT>
        <LI><FONT face=3DArial><FONT size=3D2>Intestinal =
malrotation/atresia</FONT>=20
        </FONT>
        <LI><FONT face=3DArial><FONT size=3D2>Low birth weight (less =
than 3=20
        percentile).</FONT> </FONT></LI></UL>
      <P align=3Djustify><FONT face=3DArial>Prognosis</FONT></P><FONT =
face=3DArial=20
      size=3D2>
      <P align=3Djustify>The condition is generally lethal in =
utero.</P></FONT>
      <P align=3Djustify><FONT face=3DArial>Recurrence =
risk</FONT></P><FONT=20
      face=3DArial size=3D2>
      <P align=3Djustify>Since the syndrome has an autosomal recessive=20
      transmission, the estimated recurrence risk is 25%.</P></FONT>
      <P align=3Djustify><FONT face=3DArial>Obstetrical =
management</FONT></P><FONT=20
      size=3D2>
      <P align=3Djustify><FONT face=3DArial>Determination of the fetal =
karyotype is=20
      indicated to exclude genetic syndromes (trisomy 21, 18, 13, and =
XXXXY=20
      syndromes). When the diagnosis is made before viability, the =
option of=20
      pregnancy termination should be offered to the patient. If the =
diagnosis=20
      is reached after viability, non aggressive<B> </B>management is=20
      recommended.</FONT></FONT></P>
      <P><FONT face=3DArial>References</FONT></P><FONT size=3D2>
      <P align=3Djustify><FONT face=3DArial>1. Chen H, Immuken L, =
Lachman R, et al:=20
      Syndrome of multiple pterygia, camptodactyly, facial anomalies =
hypoplastic=20
      lungs and heart, cystic hygroma, and skeletal anomalies. Am J Med =
Genet=20
      17:809-826, 1984.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>2. Martin NJ, Hill JB, =
Cooper DH, et=20
      al:Lethal multiple pterygium syndrome, Three consecutive cases in =
one=20
      family. Am J Med Genet 24:295-304,1986.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>3. Hall JG, Reed AD, =
Rosenbaum KN, et=20
      al: Limb pterygium syndrome. A review and report of eleven =
patients. Am J=20
      Med Genet 12:377-407, 1982.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>4. Mc Keown CM, Harris R: An =
autosomal=20
      dominant pterygium syndrome. J Med Genet 25:96-106 =
,1988.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>5. Hartwig NG, Vermejj-Keets =
Chr, Brujin=20
      JA, et al: Case of lethal multiple pterygium syndrome with special =

      reference to the origin of pterygia. Am J Med Genet=20
      33:537-541,1989.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>6. Moerman PH, Fryns JP, =
Carmelis A, et=20
      al: Pathatogenesis of the lethal multiple pterygium syndrome. Am J =
Med=20
      Genet 35:415-421, 1990.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>7. Bartsocas CS, Papas CV: =
Popliteal=20
      pterygium syndrome. Am J Med Genet 9:222-226, 1972.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>8. Pena SD, Shokeir BM: =
Syndrome of=20
      camptodactyly multiple ankyloses, facial anomalies and pulmonary=20
      hypoplasia: a lethal condition. J Pediatr 85:373-82, =
1974.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>9. Zeitune M., Fejgln M: =
Prenatal=20
      diagnosis of the pterygium syndrome. Prenat Diagn 8:l45-9,=20
1988.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>10. Escobar V, Bixler D, =
Gleiser S, et=20
      al: Multiple pterygium syndrome. Am J Dis Child 132:609-611,=20
      1978.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>11. Chen H, Chang CH, Misra =
RP, et al:=20
      Multiple pterygium syndrome. Am J Med Genet 7:91-102, =
1980.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>12. Chen H, Immken L, =
Lachman R, et al:=20
      Syndrome of multiple pterygium. Am J Med Genet 17:809-26, =
1984.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>13. Tolmie JL, Patrick A, =
Yates J: A=20
      lethal multiple pterygium with apparent X-linked recessive =
inheritance. Am=20
      J<B> </B>Med Genet 27:913-917, 1987.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>14. Hall JG: Editorial =
comment: The=20
      lethal multiple pterygium syndromes. Am J Med Genet 17;803-7,=20
      1984.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>15. Moessinger AC: Fetal =
akinesia=20
      deformation sequence: an animal model. Pediatrics 72:857-63,=20
      1983.</FONT></P>
      <P align=3Djustify><FONT face=3DArial>16. Papadia F, Zimbalatti F, =
Gentile La=20
      Rosa C.: The Bartsocas-Papas syndrome: autosomal recessive form of =

      popliteal pterygium syndrome in a<B> </B>male infant. Am J Med =
Genet<SUP>=20
      </SUP>17:841-847,1984<SUP>.</SUP></FONT></P></FONT>
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