Hand CONGENITAL ANAMOLIES classification.pptx

Hand Congenital anomalies

1. E MBRYOLOGY OF UPPERLIMB Dr.Harish kumar MCh Hand Surgery Resident Stanley Medical College

2. Embryonic development is a period starting from fertilization of eggs to the formation of main structure of the body, as for human beings, the 8 weeks from post-fertilization D evelopment period of limbs is basically the same as that of other human organs, and its duration is from the fourth to eighth week of embryogenesis Limb development is a three-dimensional process that occurs in the proximo-distal, radio-ulnar , and dorso -ventral axis. During the early period of embryonic development, homeobox (HOX) transcription factor mediates the skull-tail axis to start the differentiation of somites .

3. Around fourth week, the upper limb germinal area is established; the expressions of T-box (TBX5), wingless-type MMTV (WNT), and fibroblast growth factor (FGF) are established. The limb bud is first visualized at 26 days after fertilization when the embryo is about 4 mm in length (crown-rump length) M esodermal ridge appears at the ventrolateral wall of both embryonic sides and near the root of the neck segment, and it is covered with the ectoderm. U pper limb buds become clearly visible.

4. LIMB DEVELOPMENT Limb development occurs in proximo-distal direction with shoulder forming before elbow, and elbow before wrist. This progression is controlled by Apical Ectodermal Ridge(AER), a signalling centre with a thickened layer of ectoderm that condenses over the limb bud. P osition of the AER corresponds exactly to the border between dorsal ectoderm , which expresses the signaling molecule R adical fringe , and ventral ectoderm , which expresses the transcription factor Engrailed-1 (En-1). Removal of AER results in transverse deficiency, whereas an ectopic AER results in additional limb. PROXIMO-DISTAL DIRECTION

5. ANTERO-POSTERIOR The limb also develops in an anteroposterior (i.e., radioulnar or preaxial-postaxial) direction. The ZPA resides within the posterior margin of the limb bud and functions as a signaling center for anterior to posterior limb development. The signaling molecule within this pathway is the sonic hedgehog compound Transplantation of the ZPA or sonic hedgehog protein causes mirror duplication of the ulnar aspect of the limb More expression of S onic hedgehog protein may result in Mirror deformity and Post axial polydactyly. Pre axial polydactyly arise secondary to point mutations resulting in ectopic sonic hedgehog compound at the anterior margin of the limb bud

6. DORSO-VENTRAL Dorsoventral limb development, or the process of differentiation between the dorsum of the finger with a fingernail and the volar surface, The pathway produces a transcription factor, Lmx-1, which induces the mesoderm to adopt dorsal characteristics. In the ventral ectoderm, the Wnt pathway is blocked by a product of the gene Engrailed-1 (En-1). Embryo lacking the Wnt pathway may have ventralization of the dorsal surface (i.e., biventral limbs). In contrast, embryo lacking Engrailed-1 develop dorsalization of the volar surface (i.e., bi - dorsal limbs).

7. At 28–30 days of development, the upper limb bud becomes thickened and bends toward the body side At 31–32 days, the cylindrical proximal portion and the flat distal portion can be distinguished in upper limb buds, the latter of which is called hand plate;

8. A t 33 days, the upper arm, forearm, and hand plate can be distinguished in upper limb buds, by a process of selective apoptosis and even the segmented structure of hand, i.e., wrist, hand, and finger plate, can be respectively seen, but no finger-dividing sign is seen

9. At 35 days of development, finger-dividing signs appear on the hand plate of upper limb buds, and muscles and bone tissue are visible in the limb buds in mesodermal tissues, but at this stage it is unable to distinguish between the bones and muscle tissues

10. At 37 days of development, the upper limb bud development goes through the fin shape and the slurry shape, and then the fingers with traces are formed with webbed appearance.

11. At 39 days of development, the fingers are deeply webbed and palms face each other

12. A t 40–45 days, the finger begins to differentiate, and it becomes bigger and takes shape. Arm undergoes medial rotation. At this time the nerves come into the mesenchymal tissues of limb buds from the spinal cord, and muscle contour and composition is clearly visible. And the rest of mesenchymal tissues evolve into the original shape of cartilage and then become ossified to the bones At 51 days, the joints become fully evident

13. At 56 days, entire upper limb takes shape With the increase in limb length, bones are gradually formed, and the myoblasts gather and then differentiate into limb muscle group. These muscle groups are divided into extensor group at dorsal part and flexor group at ventral part.

14. SKELETAL DEVELOPMENT In the early stage of limb morphogenesis, the mesenchyme of the limb bud becomes dense by upregulation of Sox9 At around 6 weeks of development, Sox5 and Sox6 causes differentiation of chondrogenic precursors into chondrocytes, embedded in a matrix of basophils, gradually showing the characteristics of hyaline cartilage. Clavicle bone is the first bone to ossify, which appears at 7 weeks of development and contains two enchondral ossification centers at both ends, with intra membraneous ossification in the middle. The upper limb ossification centers appear in following order: humerus (8) → radius (3) → ulna (3) → distal phalanx (2) → metacarpals (2) → proximal phalanx (2) → middle phalanx (2) → carpal (1)

15. MUSCULAR DEVELOPMENT The myoblasts evolving from mesoblastic mesenchymal cell layer become aggregated locally and differentiated to myoblasts, which gradually transforms into muscle cells. Embryonic myogenesis establishes primary myotubes, later secondary myofibres surrounds the primary myofibres contributing to bulk of muscle mass at birth. Finally satellite cells in the basal lamina contribute to post natal growth and regeneration U pper limb muscles appear a little earlier than the lower limb muscles, the proximal muscles of limbs appear earlier than the distal muscles, and the extensors appear earlier than the flexors

16. VASCULAR DEVELOPMENT The primitive vascular network undergoes significant remodelling as the limb develops. By stage 13, the vascular channels coalesce proximally to form central artery(subclavian) that connects to dorsal aorta via the seventh intersegmental artery and two peripheral veins that drain into posterior cardinal system. This vascular pattern is under the direction of specific VEGF family members and VEGFR3 receptors. Later by Stage 17, axillary artery is formed followed by brachial artery and major forearm branches by stage 19

17. Initially median artery is the prominent artery, later ulnar differentiation proceeds radial differentiation forming ulnar artery, palmar carpal arch and radial artery and capillary plexus. The median and interosseus arteries continue to decrease in size. The median artery degenerates providing supply to median nerve only. By stage 21, the major vessel architecture is complete.

18. NERVE DEVELOPMENT Motor neurons begin to express various transcription factors(Hb9/ Mnx , Lhx3/4) that promote motor neuron migration into discrete columns within the spinal cord and direct their axons to specific muscle group. The cell bodies of sensory neurons reside within DRG, which is derived from neural crest cells. Nuerogenin (Ngn1/2), brain-specific homeobox/POU domain protein 3A (Brn3a), Runt homeodomain transcription factor(Runx1) are involved in cutaneous sensory neuron expression while Runx2 is involved in proprioception

19. The nerve roots, containing the motor and sensory processes from C4 to T1, coalesce to form a meshwork or plexus that eventually leads to formation of three major trunks(upper, middle and lower). The segregation of dorsal and ventral processes divides the plexus into dorsal and ventral divisions, which eventually develops into posterior, medial and lateral cords corresponding to their anatomical position. By 4 th week the brachial plexus advances into limb bud, by 5 th week nerves reaches the elbow and by 7 th week nerves reaches the fingers.

20. TIME LINE 4-6 WEEKS FORMATION 6-8 WEEKS DIFFERENTIATION 8 WEEKS TO TERM GROWTH

21. Turing Patterning Concept Described by Alan Turing is a computational model of diffusion-driven instability This depends on pattern generator within hand plate using reciprocal activator( Bmps ) and inhibitor ( Wnt ) interactions to define the alternating digit and interdigitating patterns.

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