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.
How informative is USG in picking up skeletal malformations??
Ans;-Sonography is the primary
imaging modality used for detection of an
affected fetus. The prevalence of
skeletal dysplasias identified
by ultrasound examination during
the second and third trimesters of pregnancy is about 7.5/ 10,000 pregnancies. In early pregnancy
the most frequently diagnosed skeletal
dysplasias are thanatophoric dysplasia and achondrogenesis. However
despite ultrasound findings
highly suggestive for skeletal dysplasia the definitive diagnosis should only be determined by molecular testing and confirmation of the ultrasound findings later in
preganncy summarizes the
sensitivity of 2D sonography
for the prenatal diagnosis of skeletal
dysplasias.
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