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2018, Volume 34, Number 3, Page(s) 259-261
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DOI: 10.5146/tjpath.2015.01353 |
Neu-Laxova Syndrome: An Unusual Association with Kyphosis |
Amandeep KAUR1, Vijayalaxmi SURANAGİ1, Kamal PATİL2, Hema BANNUR1 |
1Department of Pathology, KLE University, Belgaum, Karnataka, India
2Department of Obstetrics and Gynaecology, KLE University, Belgaum, Karnataka, India |
Keywords: Neu-Laxova syndrome, Lissencephaly, Kyphosis, PHGDH mutation |
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The Neu-Laxova syndrome is a rare autosomal recessive condition associated with neuro-ectodermal abnormalities and other patterns of
severe malformations leading to prenatal or early postnatal lethality. Association with kyphosis is an extremely rare finding. A fetus born
from a 25-year-old gravida at 30 weeks gestation was diagnosed with Dandy Walker syndrome with severe intrauterine growth restriction on
ultrasonography. On post-mortem examination after termination of pregnancy, the fetus showed facial dysmorphology with microcephaly,
smooth shiny skin and kyphosis. Skin histology showed hyperkeratosis, edema and increased subcutaneous fat suggestive of ichthyosis. On the
basis of gross and microscopic features seen, a diagnosis of Neu-Laxova syndrome was made. |
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The Neu-Laxova syndrome (NLS) is a rare disorder with
only 70 cases of this syndrome reported so far 1. NLS was
first reported by Richard Neu in 1971 and Renata Laxova in
1972. It is a lethal, autosomal recessive condition associated
with complex neuro-ectodermal abnormalities and other
different patterns of severe malformations. The majority of
the babies are either stillborn or die in the early neonatal
period 2. Typical features of this syndrome include skin
changes, limb abnormalities, excessive subcutaneous
edema, brain malformations and an unusual association
with kyphosis. |
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Abstract
Introduction
Case Presentation
Disscussion
References
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A 25-year-old gravida 3 para 2 living 2 woman with 30 weeks
period of gestation was referred for antenatal examination.
The fetus showed abnormal facial features and thickened
skin and was diagnosed with the Dandy-Walker syndrome
with severe intrauterine growth restriction (IUGR) on
ultrasonography. On post-mortem examination after
termination of pregnancy, the fetus weighed 375 grams,
with the length and head circumference of 27 cm and 18.5
cm respectively. All body measurements were appropriate
for 19-20 weeks of gestation. X-ray showed microcephaly,
kyphosis and enlarged orbital ridges (Figure 1). The
autopsy findings of the fetus showed microcephaly, mild
proptosis, hypertelorism, flattened nose, thickened ears,
lips, micrognathia and kyphosis. The skin was taut, shiny and thickened diffusely. Flexion contractures were seen in
the upper and lower limb. Placenta was not received.
On internal examination, the brain weighed only 15 grams
and showed flattened sulci and gyri suggestive of lissencephaly.
The brain also showed dilated lateral ventricles,
absence of corpus callosum, markedly hypoplastic cerebellum
and brain stem (Figure 2). However, dilatation of the
third ventricle was not seen. Cerebellar vermis agenesis was
not associated with fourth ventricle cyst.
Click Here to Zoom |
Figure 2: Brain showing hypoplastic brain stem and cerebellum
with absence of corpus callosum and dilated lateral ventricle. |
The thoracic and abdominal organs were normally oriented.
Microscopic sections from the skin showed hyperkeratosis,
edema and increased subcutaneous fat suggestive of
ichthyosis (Figure 3). Section from brain cortex showed
loss of neurons. Since facilities for cytogenetic studies are
not available at our institution, chromosomal status of the
fetus could not be ascertained.
Click Here to Zoom |
Figure 3: Microscopy of skin showing features of Ichthyosis
(H&E; x40). |
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Abstract
Introduction
Case Presentation
Disscussion
References
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NLS is a rare genetic disorder that is inherited as an
autosomal recessive trait. Karyotype results are normal.
Rocio Acuna-Hidalgo et al. identified homozygous
mutations in PHGDH, a gene involved in the first and
limiting step in L-serine biosynthesis, as the cause of the
disease 3. Scott et al. reported 13 cases and summarized
the components of this syndrome as abnormalities of
placentation, severe IUGR, edema, ectodermal dysplasia,
and the severe CNS developmental defect 4. Severe
IUGR is noted in 100% of the cases. The abnormalities of the head and facial (craniofacial) region i.e. microcephaly
(87%), lissencephaly (40%), absence of corpus callosum
(53%), and hypertelorism (94%) result in a distinctive facial
appearance and are the most common features 2.
NLS is characterised by abnormal accumulations of fluid
in tissues throughout the body (generalized edema), permanent flexion and immobilization of multiple joints
(flexion contractures), other limb malformations and/or
abnormalities of the brain, skin, genitals, kidneys, and/
or heart 4. The typical and diagnostic facial appearance
is peculiar to NLS. In the present case, the affected fetus
had generalised edema, microcephaly, mild proptosis,
hypertelorism, micrognathia, kyphosis, icthyosis,
lissencephaly, hypoplastic cerebellum and brain stem with
absence of corpus callosum. The weight of the brain in the
present case was 15 grams. However, Lazjuk et al. reported
a case where the brain weighed only 19.8 gm, which was the
smallest recorded weight of the brain in a 39-week gestation
5. On histological examination, there is loss of neurons
that is attributed to chromatolysis, cytoplasmic retraction,
pyknosis, and chromatin fragmentation of motor neurons
6,7. Kyphosis as seen in our case is a very rare finding and
has been reported in a case report by Hemalatha et al. 1.
Other CNS abnormalities reported include lissencephaly,
microgyria, hypoplastic cerebellum, abnormalities of
corpus callosum and lateral ventricles and aplasia of
olfactory structures and the optic nerves. The hallmark of
this syndrome is presence of excessive subcutaneous tissue
deposition with edema 8.
Several hypotheses have been proposed for these symptoms.
Karimi-Nejad et al. mentioned ichthyotic skin as the cause
of many features 9. Tos et al. claimed that the characteristic
features of NLS resemble “restrictive dermopathies”
10. This skin change leads to protein loss that causes
hypoproteinemia and polyhydramnios, generalized edema
and swollen limbs in utero. Limb deformities and flexion
contractures are also the result of these dermatopathies.
The tight skin of the fetus reduces fetal movement leading
to failure of swallowing and development of contractures.
Chromosome analysis is normal, but some genetic
alterations have been noted. Some of the recent studies on
animals showed that the genes associated with epidermal
differentiation on human chromosomes 6q and 9p must
be investigated thoroughly 10. Cerebro-oculo-facioskeletal
(COFS) syndrome is a common differential of NLS
with similar craniofacial malformations (microcephaly
with brain hypoplasia), musculoskeletal defects (flexion
contracture, micrognathia) and malformations of the brain
and spinal cord. However, the typical deep set eyes with
blepharophimosis and prominent root of the nose are in
contrast to the protruding eyes and flattened nose seen in
NLS. Several other differentials of NLS are summarised in
Table I.
The exact underlying pathogenesis of NLS still remains
unknown. But most authors believe that NLS may be a complex neuro (oculo) ectodermal dysplasia-mesenchymal
dyshistogenesis syndrome.
In conclusion, we report a rare case of NLS associated
with kyphosis, which is an uncommon presentation.
Early diagnosis of NLS with genetic counseling and serial
ultrasound examination of at-risk families is essential and
such pregnancies should be terminated. Emphasis should
be provided on public awareness in the form of genetic
counseling and risks associated with consanguinity to
reduce the incidence of NLS. |
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Abstract
Introduction
Case Presentation
Discussion
References
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1) Hemalatha A, Shilpa K, Deepthi B, Neelima P. Perinatal autopsy
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6) Squier W, Ferechte ER. Central nervous system. In: Cohen
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Abstract
Introduction
Case Presentation
Discussion
References
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