Prenatal suggestion of Pena-Shokeir I syndrome postnatally confirmed

Archives of Perinatal Medicine 16(2), 113-117, 2010
CASE REPORT
Prenatal suggestion of Pena-Shokeir I
syndrome postnatally confirmed
KRZYSZTOF PIOTROWSKI1, MARIA GIŻEWSKA2, JOLANTA WIERZBA3, STANISŁAW ZAJĄCZEK1
Abstract
We describe foetus with arthrogryposis in which on the basis of additional structural anomalies detected by USG
the Pena-Shokeir syndrome type I was suspected. Differential and final diagnosis was possible only in the
newborn, based on the characteristics of dysmorphic features. Disease lead to death by mechanism of pulmonary
dysplasia.
Key words: artrogryposis, Pena-Shokeir syndrom, prenatal detection
Introduction
Pena-Shokeir syndrome type I (PSS I) is rare autosomal recessive disease (OMIM 208150), often erroneously referred to as a sequence of defects with a fetal
akinesia without oligohydramnions, rarely with polyhydramnions.
It is usually characterized by multiple congenital flexion contractures, pulmonary hypoplasia, often low birth
weight (below 3SD), macrocephaly, dysmorphic features
(micrognathism, prominent nasal bridge with bent end,
rear nostril atresia, multiple anomalies of ears, telecantus, prominent eyes, cleft palate, short neck, camptodactyly) [1-3]. In type II PSS arthrogryposis and hypoplasia
of the lungs are usually accompanied by a microcephaly,
microphthalmia and cataract. Frequently observed malformations of the CNS are particularly localised within
the cortex and cerebellum, as well as the number of cells
in the front corners of the core are reduced and additionally, features of peripheral nemaline myopathy are
frequently detected [4-7].
Two different genes have been identified so far, that
may be responsible for various forms of syndrome: DOC
7 located in 4p16.2 and RAPSN located in 11p11; perhaps a third possibly candidate gene is located in 9q34.
Family history of disease is usually corresponding to
autosomal recessive lineage, however, sporadic cases
are frequent. Lower than in overall autosomal recesive
rate family row recursion rate suggests, that 15-20% of
the cases are heterogeneous of both forms of the syndrome [8-10].
ERCC6-CSB gene, located in 10q11, responsible for
aberrations repair, linked with Cockayne type II syndrome, has been associated with PSS II last time [4, 5].
Many possible features of the syndrome (fetal edema, cystic hygroma, CNS anomalies) can be observed
prenatally, but differentiation and definitive diagnosis is
usually possible after the birth [11-13].
The most important element, differentiating PSS I
from the other akinesia syndromes is the presence and
characteristics of fetal anomalies of the CNS [14, 15].
PSS syndrome is usually lethal during pregnancy,
rarely postnatal.
Here we present the prenatal assessment of the fetus with the PSS I and postnatal findings: dysmorphology, clinical characteristics and ultrasound features of
the child with the PSS syndrome.
Case report
23 year old primipara, not related with father of the
child, referred to the clinic at 14th of the week of gestation. Three generational pedigree analysis, apart from
simple trisomy 21 in the first degree cousin from the
mother’s, family has not shown the burden of genetic or
developmental defects.
In the first ultrasound examination, performed at
th
14 week of gestation, we found increase of nuchal
translucency up to 4 mm, hyperechogenic bowels, fetal
hypokinesia, flexion of hands. Joints of upper and lower
limbs were unaffected.
1
Cytogenetic Unit Department of Pathology of Szczecin Pomeranian Medical University of Szczecin, Poland
Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology Pomeranian Medical University
of Szczecin, Poland
2
3
Department of General Nursery and Department of Pediatrics, Hematology, Oncology and Endocrinology, Medical
University of Gdańsk, Poland
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K. Piotrowski, M. Giżewska, J. Wierzba, S. Zajączek
exclude trisomy 18, and FISH for a relatively frequent
Prader-Willi Syndrome, which also includes hypokinesia
of the fetus. Fetal karyotype was normal 46, XX and
deletion 15q11.2q13 (PWS) was excluded.
Gravida decided to continue the pregnancy, which
allowed further observation of fetal evolution. In the next
ultrasound examination at 19.5th week of gestation, hypokinesia was noticed, also flexion of large joints, but
without their deformation, flexion of hands, with correct
number overlapping fingers. We detect both feet heelalso show fingers and feet with unilateral heel foot and
recession fingers 2 and 3 in that feet.
Fig. 1. 14th week of gestation – hyperechogenic bowels
Fig. 3. 19.5th week of gestation – recession fingers 2
and 3 in that feet
a)
Level of bowel hyperechogenicity was diminished.
Structure of the brain as well as chest size and lungs
echogenicity was normal; similarly a normal heart view
and intracardiac and umbilical cord flow, normal kidneys
and amount of amniotic fluid were noted. Next five periodic sonographic examinations, showed additionally increasing retrognathia.
Fig. 2 & 2a. 15th week of gestation – abnormal feet,
in the form of "foot heel”
Other ultrasound markers of genetic deseases, including the ductus venosus flow and tricuspid valve flow
were normal. Routine biochemical triple test showed no
increased risk for trisomy 21, 13 and 18. During the next
sonographic examination in the 15th week of gestation,
further anomalies were exposed particular abnormal
feet, in the form of ”foot heel”. Further invasive diagnostics was performed, followed by karyotyping in order to
Fig. 4. 19.5th week of gestation – retrognathia
Prenatal suggestion of Pena-Shokeir I syndrome postnatally confirmed
Fetal anomalies suggested at least a dozen of different syndromes with arthrogryposis. Defects in the
hands and feet as well as retrognatia, suggested PenaShokeir syndrome, however, the final diagnosis could
not be based on equivocal prenatal screening. During
the pregnancy, neither the intrauterinal growth nor infection, nor abnormal vascular flows nor anomalies of the
placenta were observed. The course of pregnancy was
normal and ended with a labor in the 41th week of pregnancy.
Child's birth weight was 3200 g female, length 54
cm, head circumference 34 cm, Apgar 1, 3, 7. Postnatal
evaluation revealed distinct facial deformation: microophthalmia, eminent nasal bridge with curved end, long
labial groove with a thin red, large low-mounted ears,
high palate, micro- and retrognatia resulting in inability
of feeding.
115
pulmonary dysplasia was confirmed by scyntigraphic examination.
Fig. 6 & 7. Postnatally – bilateral heel-feet, and the right
site clawfoot with recession of the fingers 2 and 3
Discussion
Fig. 5. Postnatally – eminent nasal bridge with curved end,
long labial groove with a thin red, large low-mounted ears,
micro- and retrognatia
Further deformations were: short neck and broad
chest. Upper limbs were placed in flexible elbows and
wrists flexed fingers closed. Hips abducted, knees with
contractions, bilateral heel-feet, and the right site clawfoot with recession of the fingers 2 and 3.
Postnatal ultrasonographic examination of head,
heart and abdomen were normal. In contrary to prenatal
the increase of head circumference in next 4 months
was minimal (0.5 cm/month). From the birth breathing
disorders was found, continuously worsening, despite
treatment followed by pulmonary hypertension which
was the cause of death at 4 months of age. Suspected
Arthrogryposis is a condition, characterized by congenital contractures in one or more joints. Term is widely used for description of clinical symptoms, but not as
a specific diagnosis. Arthrogryposis comprises heterogeneous group of disorders involving about 300 genetically well-defined syndromes, as well as many cases of
non-specific defects. It may be a result of variety of teratogenic factors: prostaglandins, ergotamine, penicillamine, enzyme inhibitors and muscle tension lowering
agents, hyperthermia, infection and acidosis. There is an
increased risk of arthrogryposis after early amniocenthesis and CVS [16]. Many authors have linked all arthrogryposis in one group, which frequently result in erroneous conclusions [16]. PSS is not a simple sequence of
fetal akinesia, but the composed disturbances of this akinesia coexists with other symptoms.
Abnormalities observed in the fetus suggested the
possible diagnosis of at least a dozen different sets of
syndromes running with arthrogryposis. Defects in the
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K. Piotrowski, M. Giżewska, J. Wierzba, S. Zajączek
hands and feet and retrognathia narrowed the list of possible diagnoses, suggesting the PSS I syndrome, however, it could not be an unequivocal in prenatal diagnosis.
Pulmonary dysplasia is not observed in majority
other of the syndromes with arthrogryposis, and thus it
would focus prenatal differential diagnosis. The abnormal lung perfusion is typical for PSS I, distinguishing it
from PSS II. Usually direct cause of death, similarly to
the case described by us, is respiratory insufficiency, secondary to pulmonary perfusion disturbances. Ultrasonographic diagnosis of pulmonary dysplasia is difficult,
therefore testing of MRI could be necessary [17]. Akinesia of the fetus is the result of a paralysis of muscles,
including diaphragm. Abnormal amount of amniotic fluid
often prevents the growth of the lungs and causes their
hypoplasia [18-20].
The discovery of the fetus akinesia requires a long
time usg examination, in order to verify the various movable joints [11]. The diagnosis of phenotype of arthrogryposis can be put already in the first trimester of pregnancy, as occurred in this particular case.
The PSS I fenotype consist have juxta-articular contractures, muscle atrophy, camptodactyly, facial anomalies, and postnatal respiratory disorders as found in
children described. Less commonly are detected: cleft
palate and heart defects, which are not observed in our
child. Possible other symptoms of the PSS II are also:
microcephaly with extensive structural abnormalities of
CNS, microphthalmia and cataracts, which are not found,
both before and after birth [17, 21, 22, 23].
Absence of previously cases in family suggested
autosomal recessive inheritance, as it usually takes place
in the PSS. The patient was recommended of the next –
planned pregnancy – in a center providing prenatal defects diagnosis.
Direct gene testing was not available, since the global database showed only one center analyzing on DNA
level, that kind of defects for scientific purposes only [10].
Conclusion
This case demonstrate, that even the prenatal screening in I trimester of pregnancy may suggest a rare monogenic disease, but a definitive diagnosis can usually be
carried out after the birth, if at all possible.
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J
Krzysztof Piotrowski
Samodzielna Pracownia Cytogenetyki
Katedra Patologii PAM
ul. Połabska 4, 71-115 Szczecin
e-mail: kjp@onet.pl