Development of Upper Limb
&
Its congenital anomalies
Dr Anita Rani
Professor
Department of Anatomy
KGMU
!5th October 2014
Development of Limbs
• The somatic mesoderm layer of the body
wall, contributes mesoderm cells for
formation of the pelvic and shoulder
girdles and the long bones of the limbs.
• In most bones mesenchymal cells first
give rise to hyaline cartilage models,
which in turn become ossified by
Endochondral ossification .
LIMB BUDS
• 4th week: limb buds
become visible from
the
ventrolateral
body wall
• Mesenchymal core
covered by a layer of
cuboidal ectoderm.
5 weeks
HAND & FOOT PLATES / DIGITS
• While the external shape is being
established, mesenchyme in the buds
begins to condense, and these cells
differentiate into chondrocytes.
• By the 6th week of development, the first
hyaline cartilage models, foreshadowing
the bones of the extremities, are formed
by these chondrocytes.
Ossification of the bones of the extremities
• Endochondral ossification, begins by the end
of the embryonic period.
• Primary ossification centers are present in all
long bones of the limbs by the 12th week of
development.
• From the primary center in the shaft or
Diaphysis of the bone, endochondral
ossification gradually progresses toward the
ends of the cartilaginous model.
• At birth, the diaphysis of the bone is completely
ossified, but the epiphyses, are still cartilaginous.
• Ossification centers arise in the epiphyses.
• Cartilage plate (Epiphyseal plate) remains between
the diaphyseal and epiphyseal ossification centers.
• This plate, plays an important role in growth in the
length of the bones.
• Endochondral ossification proceeds on both sides of
the plate.
• When the bone has acquired its full length, the
epiphyseal plates disappear, and the epiphyses unite
with the shaft of the bone.
Formation of Joints
• Joints are formed in the cartilaginous
condensations when chondrogenesis is
arrested, and a joint interzone is induced.
• Cells in this region increase in number and
density, and then a joint cavity is formed by
cell death.
• Surrounding cells differentiate into a joint
capsule.
• Factors regulating the positioning of joints are
not clear, but the secreted molecule WNT14
Limbs Rotation
• Development of the upper and lower limbs is
similar except that morphogenesis of the
lower limb is 1 to 2 days behind that of the
upper limb.
• During the 7th week of gestation, the limbs
rotate in opposite directions.
• The upper limb rotates 90 degrees laterally.
• The lower limb rotates 90 degrees medially,
placing the extensor muscles on the anterior
surface and the big toe medially.
Positional changes of developing limbs
Molecular Regulation of Limb Development
Clinical Correlates
• Bone Age
• Radiologists use the appearance of various
ossification centers to determine whether a
child has reached his or her proper maturation
age. Useful information about bone age is
obtained from ossification studies in the
hands and wrists of children.
• Prenatal analysis of fetal bones by
ultrasonography provides information about
fetal growth and gestational age.
Limb Defects
• Limb malformations occur in approximately 6
per 10,000 live births.
• 3.4 per 10,000(upper limb).
• 1.1 per 10,000 (lower limb).
• These defects are often associated with other
birth defects involving the craniofacial, cardiac,
and genitourinary systems.
• Rare Hereditary abnormalities
Causes of Limb anomalies
• Genetic
Chromosomal anomalies (trisomy)
Mutant genes
• Environmental
Thalidomide
• Multifactorial
• Mechanical intrauterine factors
Amelia
complet
e
absence
of one
or more
of the
extremi
ties
partial
absence
of one or
more of
the
extremiti
es Phocomelia
Sometimes the long bones are
absent, and rudimentary hands
and feet are attached to the
trunk by small, irregularly
Teratogen-induced limb defects
• Many children with limb malformations were born between
1957 and 1962.
• Many mothers of these infants had taken thalidomide,a
sleeping pill and antinauseant.
• It was established that thalidomide causes absence or gross
deformities of the long bones, intestinal atresia, and cardiac
anomalies.
• Since the drug is now being used to treat AIDS and cancer
patients, there is concern that its return will result in a new
wave of limb defects.
• Most sensitive period for teratogen-induced limb
malformations is the fourth and fifth weeks of development.
Micromelia
all segments of the extremities are
present but abnormally short
•
Brachydactyly
The digits are shortened
Syndactyly
two or more fingers or toes
are fused
• Mesenchyme between prospective digits in
hand- and footplates is removed by cell death
(apoptosis).
• In 1 per 2,000 births this process fails, and the
result is fusion between two or more digits.
Polydactyly
• The presence of extra fingers or toes
• The extra digits frequently lack proper muscle
connections.
• Abnormalities involving polydactyly are
usually bilateral
Ectrodactyly
• Absence of a digit
• Usually occurs unilaterally
Cleft hand and foot
(lobster claw deformity)
• Consists of an abnormal cleft between the
second and fourth metacarpal bones and soft
tissues.
• The third metacarpal and phalangeal bones
are absent, and the thumb and index finger
and the fourth and fifth fingers may be fused.
Hand-foot-genital syndrome
• Mutations in HOXA13
• Fusion of the carpal
bones and small short
digits.
• Partially (bicornuate) or
completely (didelphic)
divided uterus
• Abnormal positioning of
the urethral orifice
• Hypospadias
Craniosynostosis–radial aplasia
syndrome
• Congenital absence or deficiency of the radius
• Absent thumbs
• Short curved ulna
Amniotic bands
• Ring constrictions and amputations of the
limbs or digits .
MCQs
•
A)
B)
C)
D)
At which week of
embryonic age limb
buds appear:
4th
5th
6th
8th
• Which of the following
factor is associated with
proximodistal growth of
limb
A) Wnt-7
B) FGF
C) Ser-2
D) ZPA
MCQs
• Amelia refers to:
A) Complete absence of
limb
B) Partial absence of limb
C) Shortening of limb
D) Absence of finger
• Which of the following
mesoderm will give rise
to bones of the limb
A) Extra embryonic
B) Paraxial
C) Intermediate
D) Lateral plate
MCQs
• Which of the following
IUL period is most
susceptible for
teratogen induced limb
deformities:
• A) First & Second wks
• B) Second & third wks
• C) Third & Fourth wks
• D) Fourth & Fifth wks
Secondary ossification
centers appear in
A) Diaphysis
B) Epiphysis
C) Metaphysis
D) In both diapysis &
epiphysis