Development of the Limbs

Limb Formation

• Day 24: appearance of upper limb bud
• Day 26: appearance of lower limb bud

• Week 5: tail segment present between lower limbs → gradually disappears
• Limb bud: 
  • Location: ventrolateral aspect of the body
  • Coming from lateral plate mesoderm Mesoderm The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube. Gastrulation and Neurulation initiated by fibroblast growth factor Fibroblast growth factor A family of small polypeptide growth factors that share several common features including a strong affinity for heparin, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family. X-linked Hypophosphatemic Rickets 10 (FGF10)
  • Covered by ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation
  • Has a core of denser condensed mesenchyme
  • At the tip: apical ectodermal ridge (AER)
  • Position:
    • Upper limb bud: opposite to caudal cervical segment Cervical segment Spinal Cord: Anatomy
    • Lower limb bud: opposite to lumbar and sacral segments
• AER:
  • Part of the ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation that underlies the limb bud
  • Produces FGF8 to maintain elongation Elongation Polymerase Chain Reaction (PCR) of the limbs
• AER exerts influence on surrounding tissue to keep it undifferentiated:
  • As AER migrates away, more proximal tissue differentiates into cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology and muscle.
  • Limbs form proximally to distally in segments:
    • Stylopod: humerus Humerus Bone in humans and primates extending from the shoulder joint to the elbow joint. Arm: Anatomy and femur
    • Zeugopod: radius Radius The outer shorter of the two bones of the forearm, lying parallel to the ulna and partially revolving around it. Forearm: Anatomy/ ulna Ulna The inner and longer bone of the forearm. Forearm: Anatomy and tibia Tibia The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the fibula laterally, the talus distally, and the femur proximally. Knee Joint: Anatomy/ fibula Fibula The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. Leg: Anatomy
    • Autopod: carpals Carpals The eight bones of the wrist: scaphoid bone; lunate bone; triquetrum bone; pisiform bone; trapezium bone; trapezoid bone; capitate bone; and hamate bone. Wrist Joint: Anatomy, metacarpals Metacarpals The five cylindrical bones of the metacarpus, articulating with the carpal bones proximally and the phalanges of fingers distally. Wrist Joint: Anatomy, digits/tarsals, digits/metatarsals
• Hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy and foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy plates form as upper and lower limbs extend:
  • Initially appear like fused paddles around 6th week
  • Digital rays: appear as webbed tissue between fingers begins to undergo apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage
  • Day 52–56: Fingers and toes appear.

Mnemonic:

To quickly recall what happens during the 4th week, remember: 4 weeks → 4 limbs, 4 heart chambers

Rotation of the Limbs

• As the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week changes from a flat disk to a 3-dimensional structure, the limbs rotate.
• Upper limb:
  • Week 4: Limb buds emerge from coronal Coronal Computed Tomography (CT) plane.
  • Week 6: Limb buds move toward sagittal plane Sagittal plane Anterior Abdominal Wall: Anatomy.
  • Weeks 6–8: lateral 90-degree rotation Rotation Motion of an object in which either one or more points on a line are fixed. It is also the motion of a particle about a fixed point. X-rays: 
    • Flexor compartments shifted anteriorly
    • Elbows located posteriorly
    • Proper allocation of dermatome Dermatome Spinal Disk Herniation innervation
• Lower limb:
  • Week 4: Limb buds emerge from coronal Coronal Computed Tomography (CT) plane.
  • Week 6: Limb buds move toward sagittal plane Sagittal plane Anterior Abdominal Wall: Anatomy.
  • Weeks 6–8: medial 90-degree rotation Rotation Motion of an object in which either one or more points on a line are fixed. It is also the motion of a particle about a fixed point. X-rays: 
    • Flexor compartments located posteriorly
    • Extensor compartments located anteriorly

Formation of Musculature

Overview

Muscle comes from myotome: ventrolateral cells originating from somites located on either side of neural tube Neural tube A tube of ectodermal tissue in an embryo that will give rise to the central nervous system, including the spinal cord and the brain. Lumen within the neural tube is called neural canal which gives rise to the central canal of the spinal cord and the ventricles of the brain. Gastrulation and Neurulation that migrate to form muscles. As myotomes migrate, they form:

• Epimere (epiaxial):
  • Cluster of developing muscle from the myotome
  • Goes into the back → future intrinsic muscles of the back Muscles of the back The back is composed of several muscles of varying sizes and functions, which are grouped into intrinsic (or primary) back muscles and extrinsic (or secondary) back muscles. The extrinsic muscles comprise the superficial and intermediate muscle groups, while the intrinsic muscles comprise the deep muscles. Muscles of the Back: Anatomy
• Hypomere (hypoaxial):
  • Travels into the torso → anterior thoracic wall → abdominal wall Abdominal wall The outer margins of the abdomen, extending from the osteocartilaginous thoracic cage to the pelvis. Though its major part is muscular, the abdominal wall consists of at least seven layers: the skin, subcutaneous fat, deep fascia; abdominal muscles, transversalis fascia, extraperitoneal fat, and the parietal peritoneum. Surgical Anatomy of the Abdomen → limbs
  • Extends ventrolaterally
  • Forms body-wall and limb muscle
  • After migration to the limb buds, they separate again:
    • Posterior mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast (dorsal) → extensor muscles
    • Anterior mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast (ventral) → flexor muscles

Upper limbs

• Somites give rise to the musculature of levels C4–C8, T1–T2.
• Posterior condensation gives rise to extensor and supinator Supinator Forearm: Anatomy muscles.
• Anterior condensation gives rise to flexor and pronator muscles.

Lower limbs

• Somites that give rise to the musculature of levels L1–L5, S1 S1 Heart Sounds– S2 S2 Heart Sounds
• Posterior condensation: gives rise to the extensor and abductor muscles
• Anterior condensation: gives rise to flexor and adductor muscles

Nerve innervation

• Somites give rise to the musculature of levels L1–L5, S1 S1 Heart Sounds– S2 S2 Heart Sounds.
• Posterior condensation gives rise to extensor and abductor muscles.
• Anterior condensation gives rise to flexor and adductor muscles.
• Upper limbs: C4–T2
• Lower limbs: L4– S3 S3 Heart Sounds
• Nerves get stretched from the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy as upper and lower limbs develop: Brachial and lumbosacral plexus are made.

Development of Vasculature

• Blood vessels invade developing musculature around 35–36 days of gestation.
• Upper limb: segmental artery → axillary artery Axillary Artery The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. Axilla and Brachial Plexus: Anatomy
• Lower limb: segmental artery → femoral artery Femoral Artery The main artery of the thigh, a continuation of the external iliac artery. Femoral Region and Hernias: Anatomy
• Initially, arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology go to the limb buds → enlarge but stay deep → capillaries Capillaries Capillaries are the primary structures in the circulatory system that allow the exchange of gas, nutrients, and other materials between the blood and the extracellular fluid (ECF). Capillaries are the smallest of the blood vessels. Because a capillary diameter is so small, only 1 RBC may pass through at a time. Capillaries: Histology form
• Venous drainage is more superficial.
• No superficial arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology at the core of the limbs

Development of Limb Bones and Joints

Limb bones

• Limb buds condense → Models of hyaline cartilage Hyaline cartilage A type of cartilage characterized by a homogeneous amorphous matrix containing predominantly type II collagen and ground substance. Hyaline cartilage is found in articular cartilage; costal cartilage; laryngeal cartilages; and the nasal septum. Cartilage: Histology begin to form.
• Endochondral ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification: mesenchyme → cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology → bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types:
  • Mesenchyme: loose, undifferentiated connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
  • Cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology: tougher, avascular Avascular Corneal Abrasions, Erosion, and Ulcers; relies on diffusion Diffusion The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space. Diffusion, especially facilitated diffusion, is a major mechanism of biological transport. Peritoneal Dialysis and Hemodialysis
• Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types collar:
  • Layer of periosteum Periosteum Thin outer membrane that surrounds a bone. It contains connective tissue, capillaries, nerves, and a number of cell types. Bones: Structure and Types that surrounds the diaphysis Diaphysis The shaft of long bones. Bones: Structure and Types
  • Formed by osteoblasts Osteoblasts Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. Bones: Development and Ossification
• Primary ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification center:
  • Forms diaphysis Diaphysis The shaft of long bones. Bones: Structure and Types—shaft of the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types containing bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis cavity
  • Artery invades middle of the cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology → brings osteoprogenitor cells
  • Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types formation proceeds outward
• Secondary ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification center:
  • Forms epiphysis Epiphysis The head of a long bone that is separated from the shaft by the epiphyseal plate until bone growth stops. At that time, the plate disappears and the head and shaft are united. Bones: Structure and Types
  • At the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types extremities
  • Separated from primary ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification center by metaphysis Metaphysis Bones: Structure and Types
• Alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma: 
  • Produced by chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology
  • Responsible for mineral deposition on bones
• Primary and secondary ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification centers get closer → Epiphyseal growth plate tries to proliferate and push them away.
• Epiphyseal plates remain open until the early 20s → bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types can no longer elongate, and growth arrests
• Medullary cavity Medullary Cavity Ewing Sarcoma: 
  • Formed by the action of osteoclasts Osteoclasts A large multinuclear cell associated with the bone resorption. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. Bones: Development and Ossification
  • Core of diaphysis Diaphysis The shaft of long bones. Bones: Structure and Types
  • Major site of hematopoiesis Hematopoiesis The development and formation of various types of blood cells. Hematopoiesis can take place in the bone marrow (medullary) or outside the bone marrow (extramedullary hematopoiesis). Bone Marrow: Composition and Hematopoiesis

Joints

• Mesenchyme between the bones stays as dense irregular connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology.
• Synovial spaces form as the bones grow through the complex process of apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage.
• Intracapsular ligaments ( anterior cruciate ligament Anterior Cruciate Ligament A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. Knee Joint: Anatomy ( ACL ACL A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. Knee Joint: Anatomy) and posterior cruciate ligament Posterior Cruciate Ligament A strong ligament of the knee that originates from the anterolateral surface of the medial condyle of the femur, passes posteriorly and inferiorly between the condyles, and attaches to the posterior intercondylar area of the tibia. Knee Joint: Anatomy ( PCL PCL A strong ligament of the knee that originates from the anterolateral surface of the medial condyle of the femur, passes posteriorly and inferiorly between the condyles, and attaches to the posterior intercondylar area of the tibia. Knee Joint: Anatomy)):
  • Remnants of connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology
  • Dense and regular Regular Insulin

Genetic and Molecular Patterning of Limbs

Positioning, orientation Orientation Awareness of oneself in relation to time, place and person. Psychiatric Assessment, and growth of limbs in the developing embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week is determined genetically and by the expression of specific timed chemical signals.

Craniocaudal axis

Positioning of limbs along the craniocaudal axis is determined by the homeobox (HOX) genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure.

• This segment of genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure (60 amino acids Amino acids Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. Basics of Amino Acids long) encodes for DNA-binding proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, which regulate gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics expression.
• The HOX-containing genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure regulate multiple aspects of cell growth and differentiation. 
• These genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure are arranged sequentially in a cranial-to-caudal manner, and they determine the overall pattern and shape of the developing embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week. 
• For example:
  • HOXB8 expressed at cranial border of forelimb
  • Mutations in this gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics alter the position of these limbs. 
  • Forelimb positioning is determined by the transcription factor Transcription factor Generic term for proteins necessary for transcription Regulation of Transcription T-box transcription factor Transcription factor Generic term for proteins necessary for transcription Regulation of Transcription 5 (TBX5); hindlimb positioning is determined by TBX4.

Proximodistal axis

• Proximodistal patterning is regulated by maintaining the AER distally as the embryo Embryo The entity of a developing mammal, generally from the cleavage of a zygote to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the fetus. Fertilization and First Week develops.
• Radical fringe is a signaling factor expressed in the dorsal ½ of the limb ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation:
  • Induces the expression SER2 at the border between cells that are expressing radical fringe and those that are not
  • AER is localized to that border.
• Once AER is developed:
  • Expresses multiple classes of FGF 
  • Maintains the undifferentiated area of profusely replicating mesenchyme cells immediately proximal to the AER
  • As the cells duplicate, the limb grows distally.
  • The further the mesenchymal cells are from the AER, the less FGF can influence the mesenchymal cells, which can then differentiate thanks to the influence of other signaling molecules Signaling molecules Second Messengers:
    • Retinoic acid: synthesized by flank mesenchyme, causes differentiation of tissue into stylopod 
    • Sonic hedgehog (SHH): expression of this gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics leads to differentiation of the zeugopod and autopod

Anteroposterior axis

• Regulated by zone of polarizing activity (ZPA)
• A cluster of mesenchymal cells in the posterior portion of the limb, near the AER
• Secrete the signaling factor SHH
• The expression of SHH determines the correct anteroposterior orientation Orientation Awareness of oneself in relation to time, place and person. Psychiatric Assessment of limbs; e.g., misexpression of SHH in the anterior portion of the hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy can lead to digit duplication.

Dorsoventral axis

• Ventral ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation expresses the transcription factor Transcription factor Generic term for proteins necessary for transcription Regulation of Transcription EN1.
• EN1 blocks the secretion Secretion Coagulation Studies of WNT7a:
  • WNT7a is therefore localized to the dorsal ectoderm Ectoderm The outer of the three germ layers of an embryo. Gastrulation and Neurulation.
  • Induces expression of LMX1 → a transcription factor Transcription factor Generic term for proteins necessary for transcription Regulation of Transcription that specifies “dorsal” orientation Orientation Awareness of oneself in relation to time, place and person. Psychiatric Assessment

Clinical Relevance

• Achondroplasia: mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in FGFR3 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics and corresponding protein that has a negative effect on endochondral ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification. Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations causes overactivity of the receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors signaling pathway, which results in impaired growth and proliferation of chondrocytes Chondrocytes Polymorphic cells that form cartilage. Cartilage: Histology. Affected individuals tend to have shortened limb bones, and facial bones do not elongate.
• Sirenomelia: also called mermaid syndrome. Sirenomelia is a rare congenital Congenital Chorioretinitis deformity Deformity Examination of the Upper Limbs in which the legs are fused together. The disorder is mainly characterized by the fusion of the legs with rotation Rotation Motion of an object in which either one or more points on a line are fixed. It is also the motion of a particle about a fixed point. X-rays of the fibula Fibula The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. Leg: Anatomy. Sirenomelia may also include absence of the lower spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy and abnormalities of the pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy and renal organs. Sirenomelia has a poor prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas, with most infants not surviving the 1st year of life.
• Syndactyly: Cutaneous syndactyly is webbing between the digits. Syndactyly occurs because of the failure of apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage, which is responsible for the separation of the digits. Osseous syndactyly consists of fusions of the bones of the digits.
• Amelia: absence of 1 or both limbs, which occurs because of suspension in development during the 4th week.
• Meromelia: condition in which a part of the limb is missing. Meromelia occurs because of a disturbance in development during the 5th week of gestation. Examples include hemimelia (absence of fibula Fibula The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. Leg: Anatomy) and phocomelia (hands and feet attached directly to the body).