Author
Information
Shruti Panchbudhe*,
Vibha More*, Kimaya Mali
(* Assistant Professor, ** Professor, ***
Second
year Resident. Department of
Obstetrics and Gynecology, Seth G. S. Medical College & K.E.M.
Hospital , Mumbai , India
Abstract
We
describe a rare case of lethal multiple pterygium syndrome which was diagnosed
prospectively at 16 weeks of gestation in a fetus without a family history of
the disorder. Diagnosis was based on antenatal sonographic demonstration of
severe limb contractures, absence of fetal limb movements, and a large cystic
hygroma.
Introduction
The prevalence of multiple
pterygium syndrome is unknown. This condition is inherited as an autosomal
recessive pattern and some cases are also inherited in a X-linked recessive
manner.[1] The mutation in “cholinergic receptor, nicotinic, gamma”
(CHRNG ) located on 2q37.1 is responsible for development of this
syndrome. The mutation in the CHRNG gene results in a defective or missing γ
subunit of the Acetyl Choline Receptor (AChR) and severity of the this gene
mutation influences the severity of the condition. Lethal type results when
there is no production of any γ subunit , while mutations that allow the
production of some γ subunit will lead to the Escobar type of multiple
pterygium syndrome.[2] In the absence of this functional γ subunit,
the fetal AChR protein is not assembled properly in the muscle cell membrane
and the communication between nerve cells and muscle cells in the developing
fetus is impaired. This results in a fetal akinesia sequence which leads to
early embryonic immobility due to which the skin grows over the underlying
joints, leading to formation of multiple pterygium.
Case report
A 28 year old woman, 5th
gravida with previous four first trimester abortions presented to the antenatal
outpatient department at 6 weeks of gestation for antenatal registration. She
had history of consanguineous marriage. Her previous pregnancies were missed
abortions at around 2 months of gestation, for which suction evacuation was
done. She was being evaluated by a private practitioner for bad obstetric
history. Her parental karyotyping was normal. Thrombophilia profile with
protein C, protein S, Anti thrombin III, Factor V Leiden mutation had already
been done prior to this conception and found to be within normal limits. She
was negative for Anti nuclear antibody, double stranded DNA, Lupus
anticoagulant and Antiphospholipid antibody. TORCH titres were done which ruled
out active infection. Her Thyroid stimulating hormone and glycosylated
haemoglobin were in normal limits. Her blood group was Rh positive. She was
started on periconceptional folic acid. In this present pregnancy she had
spotting per vaginum at 6 weeks of gestation. On speculum examination there was
minimal bleeding and on vaginum examination uterus was anteverted, 6 weeks,
bilateral fornices were free and non tender and external os was closed. She was
admitted as a case of threatened abortion with bad obstetric history. There was
no further episode of spotting and ultrasonography confirmed a single live
intrauterine gestation with gestational sac diameter of 24.4 mm, corresponding
to gestational age of 6.4 weeks. She was started on low dose aspirin and
micronised progesterone. Her first trimester screening scan was done at 12
weeks of gestation which showed a cystic lesion in the posterior part of the
neck with septations suggestive of cystic hygroma and was advised chorionic
villous sampling to rule out aneuploidies. A detailed malformation scan was done at 16
weeks of gestation which showed multiple malformations in the baby like cystic
hygroma of 4×5 cm, body wall oedema, scalp oedema, pericardial effusion with
all four limbs fixed in one position with no movement of the limbs. Chorionic
villus sampling report was suggestive of normal karyotype in 37 of the 40
metaphases but three metaphases (7.5%) showed structural chromosomal anomalies
like deletion of the terminal region of 9q, additional material on 9q and additional
material on 17q in 1 metaphase each. On the basis of these findings, the patient
and her relatives were explained about the poor fetal prognosis and they opted
for termination of pregnancy. A second trimester medical
termination pregnancy was done with misoprostol.. The weight of the abortus was
240 g and morphological appearance showed multiple pterygium at the neck,
elbow, fingers, knee with cystic hygroma, malformed ribs, and atypical facial
features which clinched the diagnosis of lethal type of multiple pterygium
syndrome.
Figure 1.
Ultrasonography showing fixed lower limbs at the knee joint with no fetal
movements.
Figure 2. Chromosomal
analysis report of chorionic villi.
Figure 3. Chromosomal
analysis report of chorionic villi.
Figure 4. A and B:
Anterior view of fetus having multiple pterygium at the neck, elbow, wrist, knee and ankle, syndactyly
of the fingers, orofacial anomalies and rib defects; C: Lateral view. Note low
set ears, rib defects and a appendage at
the sacral region.
Discussion
Multiple pterygium
syndrome is a condition that can be diagnosed in the antenatal period and is
classified into two types; Escobar (nonlethal) and Lethal types. They are
differentiated by the severity of their symptoms. Escobar type is the milder variety
and Lethal type is fatal before birth or very soon after birth. The majority of fetuses with the Lethal disorder die in utero, and the those
few who survive pregnancy develop pulmonary hypoplasia in the early neonatal
period.
In multiple pterygium syndrome of
the Escobar type, there is webbing typically affecting the skin of the neck,
fingers, forearms, inner thighs, and backs of the knee .They may also have
short stature, lung hypoplasia, arthrogryposis, scoliosis, orofacial features
including ptosis, downslanting palpebral fissures, hypertelorism, long philtrum
, small mouth, epicanthal fold, micrognathia, cleft palate, cleft lip and
low-set ears. Musculoskeletal abnormalities include multiple flexion
contractures, rib anomalies, vertebral anomalies like scoliosis, lordosis, congenital
hip dislocation, soft tissue syndactly of the fingers, rocker bottom feet and
talipes equinus. Males with this condition can have cryptorchidism and females
can have absent labia majora. Escobar type does not deteriorate after birth as γ
subunit found in the fetal AChR protein is replaced by
another subunit to form adult AChR protein at
thirty-third week of pregnancy and this is the reason most people with
this type do not have problems with muscle movement after birth and later in life.[3]
Lethal multiple pterygium syndrome has many of the features of the
Escobar type. In addition affected foetuses may develop hydrops fetalis and
cystic hygroma which is present in majority of the patients. They have severe
arthrogryposis, hypoplasia of the lung, brain dysgenesis including
hydranencephaly, cardiac hypertrophy, intestinal malrotation, cleft palate,
cleft lip and microcephaly. Intestinal
abnormalities, ocular defects such as cataracts, renal abnormalities like hydronephrosis
or dysplastic kidneys, short umbilical cord, and a wide range of skeletal
abnormalities, such as hypoplasias of spine, malformed ribs, syndactly of the
fingers and hip dislocations are also found. Affected individuals may also
develop congenital diaphragmatic hernia.[4]
Lethal
multiple pterygium syndrome is further subdivided into a number of subtypes,
including lethal multiple pterygium syndrome with spinal fusion, lethal
popliteal pterygium syndrome, and lethal multiple pterygium syndrome with
congenital bone fusion. But this classification does not hold true recently
because different subtypes are found in the same families.
In most prior reports, the diagnosis was made retrospectively on the basis of
autopsy findings or depended on a family history. In the current case,
antenatal diagnosis was based on identification of the characteristic
combination of severe fixed limb contractures, cystic hygroma, and hydrops, malformed
ribs and syndactly of the fingers in a patient without family history of this
syndrome. Lethal multiple ptygerium syndrome may have a normal 46,XX or 46,XY karyotype and
determining the fetal karyotype is an important step in confirming the
diagnosis, since some of the abnormalities like cystic hygroma have a high association with chromosomal aneuploidies.
The differential diagnosis
includes Pena-Shokeir syndrome, congenital myotonic
dystrophy, arthrogryposis multiplex congenita and nonlethal pterygium syndrome.
References
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Citation
Panchbudhe S, More V, Mali