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 appears
to be the inductive signal.
 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
complete
absence
of one or
more of
the
extremiti
es
Meromelia
partial
absence of
one or more
of the
extremities
Phocomelia
Sometimes the long bones are
absent, and rudimentary hands
and feet are attached to the trunk
by small, irregularly shaped bones
 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
• A combination of syndactyly and
polydactyly (synpolydactyly).
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
• At which week of
embryonic age limb Which of the following
buds appear: factor is associated with
A) 4th proximodistal growth of
B) 5th limb
C) 6th A) Wnt-7
B) FGF
D) 8th
C) Ser-2
D) ZPA
 MCQs
• Amelia refers to:
A) Complete absence of
Which of the following
limb
mesoderm will give rise to
B) Partial absence of limb bones of the limb
C) Shortening of limb A) Extra embryonic
D) Absence of finger B) Paraxial
C) Intermediate
D) Lateral plate
 MCQs
• Which of the following
IUL period is most
susceptible for Secondary ossification
teratogen induced limb centers appear in
deformities: A) Diaphysis
• A) First & Second wks B) Epiphysis
C) Metaphysis
• B) Second & third wks D) In both diapysis &
• C) Third & Fourth wks epiphysis
• D) Fourth & Fifth wks