which
dysplasia are lethal??Ans;- Short Femur length and prediction of lethality in skeletal
dysplasias .
Fetuses with skeletal dysplasias in which
all lethal cases were associated with a femur length abdominal
circumference ratio of 0.16 . Although
the test detected lethal
cases with 100 % sensitivity few cases
of achondroplasia were erroneously
identified as lethal using this
method. A different approach has been proposed which mentions lethality
in 23 out of 25 cases of skeletal dysplasias with a femur length below
the 1st percentile for gestational
age and presence of bell
shaped thorax or decreased
bone echogenicity. If one cannot
estimate many important diameters necessary to confirm the diagnosis of skeletal
dysplasia / due possibly to time constraints then a femur/ abdominal
circumference ratio less than
0.16 have to be measured as a minimum.
In fact F/ AC is the
main discriminator among fetuses
with lethal skeletal dysplasias
and that this measurement
has still a better
performance than a) femur
shortening b) thoracic
circumference and c) thoracic circumference/ abdominal circumference ratio.
Which gene has undergone mutation?? :-- Till date it is known that about 25%
of all bone disorders the mutated gene has not been
yet identified . What is the
classification of constitutional disorders of bone ?? Ans:- Skeletal
dysplasias are a heterogeneous
group of disorders affecting the
development of chondro-osseous tissues leading to abnormalities in the size , mineralization and
shape of various segments of the skeleton. Despite recent advances in imaging and molecular genetics accurate prenatal diagnosis of skeletal
dysplasias remains a clinical
challenge. In the most recent
revision of the International
Nosology and Classification of Constitutional disorders of bones , it is mentioned that in approximately 25%
of all bone disorders the mutated gene has not been
yet identified.
What
does International skeletal
Dysplasia Registry tells us??
:--It is important to acknowledge the contribution of the International skeletal
Dysplasia Registry in the identification and study
of skeletal anomalies assisting
providers and patients
in the diagnosis and
clinical management of skeletal
disorders. This registry informs us that a-twenty three percent of the affected infants were stillborn whereas 32%
died during the first week of
life. The overall frequency of skeletal
dysplasias among perinatal deaths
was 9.1/1000.
c) How
significant is incidental solo findings of “short femoral length at
late trimester” ?? Will we be
worried?? Concern to the Obstetrician is “Am I dealing with normal biological variant/ real
pathology of bone so called –“skeltal dysplasia” ?? Ans:- Significance
of short femoral length if noticed at mid to late
third trimester “” This is not
unusual for the femur to be significantly shorter than the
other measurements used to estimate gestational age. In many cases the femur is approximately 2 weeks less than
the head circumference and menstrual age. The cause of
this is often uncertain and the short
femur is often attributed to biologic variation or ethnicity. If the bones appear normal morphologically and no other anomalies are seen it is likely a normal variant.
One
week less is permissible. Short F L . But my dear members this even 1 week lag may rarely be due
to 1) a sign of trisomy 21 or 2) an early manifestation of a short limb skeletal
dysplasia. :-- One should
acknowledge that a fetus from white
parents of normal height and middle socioeconomic status will have a standard FL which one
should not compare with that of FL of Indian parents of low socioeconomic status . Although
the femur can be smaller than
other measurements in the third trimester
it is not acceptable for it to be greater than 1 week less than the other
measurements in the late first and early
to mid second trimesters.
Although this deviation may be nothing more than
a temporary growth lag
or normal
variation at this stage
, it may also be 1) a sign of trisomy
21 or 2) an early
manifestation of a short limb
skeletal dysplasia.
This may be a case
of trisomy 21 as well . One should
not take comfort in comparing the femur measurement to the
estimated gestational age by ultrasound imaging . Remember that unless excluded the femur measurement is included in the sonographic estimation of gestational
age.
Classification of Genetic
skeletal disorders—As many as 364 genes may be involved in the etiology of
skeletal dysplasia !!! :- . Most skeletal
anomalies are a phenotypic manifestation of a mutation
in a gene and altered protein expression therefore they can be grouped according to the
affected genes as they
share similar clinical
characteristics. The International skeletal
dysplasia Society
periodically reviews this. But with the advent of “sequencing technologies and the
increasing availability of whole exome sequencing”-- allowing the discovery of more gene
related skeletal anomalies. With these technologies as many as 436
clinical conditions were classified into 42 groups involving 364 affected
genes . The classification provides the A) group/ name of the skeletal
disorder B) type of inheritance; C) MIM number ; D) locus
of the mutation in the gene
, F) affected protein and F) associations/
difference with other skeletal
anomalies . International
Nosology and Classification of Constitutional disorders of bones & International
skeletal Dysplasia Registry:-- Also tell us classification includes:-Skeletal dysplasias , metabolic
bone disorders, dysostosis
, skeletal malformations and
reduction syndromes are included in this
classification . However
the authors also clarify that in
approximately 25% of skeletal
disorders the mutated gene
has not yet been identified . The genetic basis
for classification of very
rare diseases was done
by family pedigree or was
based on homogeneity or phenotype
in unrelated families. The classification aims to provide more complete information
for prenatal counseling and clinical management
. The full document can be consulted ate the ISDS website.
Shortening
of the extremities can involve the entire
limb , or the proximal segment only, or the intermediate segment
or only to the distal segment . What is meant by rhizomelia ?? Ans:-The diagnosis of rhizomelia or mesomelia requires comparing the bony dimensions of the lower legs and forearms with those of the thighs and arms . The relationships between
the humerus and ulna as well as the
femur and tibia which can be used for the objective assessment
of rhizomelia and mesomelia presents
a list of skeletal dysplasias
characterized by rhizomelia, mesomelia and micromelia.
There
are several skeletal dysplasias which feature alternation of the hands and feet. The term A) polydactyly refers to the
presence of more than five digits. It is classified as postaxial
if the extra digits are on the
ulnar or fibular side and preaxial if they are located
on the radial or tibial side . B) By contrast Syndactyly refers to
soft tissue or bony fusion of adjacent digits. C) Clinodactyly consists
of deviation of a finger or
fingers.
defect in a given case is not that easy: Despite increasing
availability of molecular testing in about one third of skeletal
dysplasias their molecular basis has
not been defined. The role of
diagnostic imaging in the prenatal investigation of skeletal dysplasia to narrow the differential diagnosis of skeletal dysplasias so that appropriate confirmatory molecular
tests can be done to predict lethality
and to identify the fetus with a skeletal dysplasia early enough in gestation so that the diagnostic workup
can be completed before the
limit of fetal viability.
Lung volumetry by three dimensional sonography: can it help to identify the
lethality of skeletal dysplasia ?? Ans:- . Fetal lung volumetry by 3D sonography
has been performed using two
techniques multiplanar and VOCAL
. Nomograms for lung volumetry
using 3D sonography are available
in the literature . Both the 3D
multiplanar and 3D VOCAL
modes can be used to measure
fetal lung volumes an
observation that was subsequently
. A potential advantage of the VOCAL
technique is the possibility of obtaining
fine contours of the lungs which
may be particularly valuable
when the outline of the organ is irregular such as in cases
of congenital diaphragmatic
hernia. In contrast
obtaining lung volume measurements using the 3D multiplanar
technique is faster taking usually less than 5 minutes to perform . Volumes are best estimated when datasets are acquired using a transverses view of the fetal thorax. compared volumetric measurements of the fetal
lungs obtained using the
VOCAL method with lung volumes calculated at the time of autopsy
in 8 cases of congenital diaphragmatic hernia and in 25
control fetuses without
pulmonary malformation. The mean relative error of 3D
sonography to estimate the actual
lung volume was -7.19 % in cases of
congenital diaphragmatic hernia and
-0.72 % in normal fetuses . Barros and colleagues studied
24 fetuses with skeletal dysplasia and measured the total lung volume
using VOCAL . an abnormally
reduced lung volume was defined
as below the 5th percentile
for gestational age . From 18 fetuses diagnosed at birth with lethal pulmonary hypoplasia.
83% had a total lung volume below the 5th percentile for gestational age. Lung volume
more accurately predicted
pulmonary hypoplasia than thoracic
circumference thoracic circumference / abdominal circumference ratio and thoracic area/ cardiac area ratio .
. Skeletal Dysplasias
characterized by Rhizomelia ,
Mesomelia and Micromelia What is platyspondyly ?? Ans:-The most common spinal abnormality seen in skeletal dysplasias is platyspondyly which consists
of flattening of the vertebrae .
Xyphhosis scoliosis and coronal
clefting of vertebral bodies
have been also reported.
Types
of skeletal defects : Rhizomelia ,Thanatophoric dysplasia
Atelosteogenesis
Chondrodysplasia punctata
Congenital
short femur
Achondroplasia
Hypochondroplasia
Mesomelia
Mesomelic dysplasia
Ellis- van
Creveld syndrome
Acromesomelia
Ellis- van Creveld syndrome
Micromelia
Achondrogenesis
Atelosteogenesis
Short
rib- polydactyly syndrome
Diastrophic dysplasia
Fibrochondrogenesis
Osteogenesis imperfect
Kniest dysplasia
Dyssegmental
dysplasia
Roberts
syndrome
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