Hoxa13 Hoxd13

5q35 7p21

2q31

Pfeiffer syndrome

Pfeiffer syndrome Apert syndrome

Jackson-Weiss syndrome

Crouzon syndrome

Achondroplasia

Thanatophoric dysplasia (type I) Thanatophoric dysplasia (type II) Hypochondroplasia

Boston-type craniosynostosis Saethre-Chotzen syndrome

Hand-foot-genital syndrome Synpolydactyly

Craniosynostosis, broad great toes and thumbs, cloverleaf skull, underdeveloped face Same

Craniosynostosis, underdeveloped face, symmetric syndactyly of hands and feet Craniosynostosis, underdeveloped face, foot anomalies, hands usually spared Craniosynostosis, underdeveloped face, no foot or hand defects Short-limb dwarfism, underdeveloped face Curved short femurs, with or without cloverleaf skull Relatively long femurs, severe cloverleaf skull Milder form of achondroplasia with normal craniofacial features Craniosynostosis

Craniosynostosis, midfacial hypoplasia, cleft palate, vertebral anomalies, hand and foot abnormalities Small, short digits, divided uterus, hypospadius Fused, multiple digits consist of a mesenchymal core derived from the somatic layer of lateral plate mesoderm that will form the bones and connective tissues of the limb, covered by a layer of cuboidal ectoderm. Ectoderm at the distal border of the limb thickens and forms the apical ectodermal ridge (AER) (Fig. 8.13A). This ridge exerts an inductive influence on adjacent mesenchyme, causing it to remain as a population of undifferentiated, rapidly proliferating cells, the progress zone. As the limb grows, cells farther from the influence of the AER begin to differentiate into cartilage and muscle. In this manner development of the limb proceeds proximodistally.

In 6-week-old embryos the terminal portion of the limb buds becomes flattened to form the handplates and footplates and is separated from the

Dwarfism Fig

Figure 8.10 A. Three-month-old infant with achondroplasia. Note the large head, short extremities, and protruding abdomen. B and C. Achondroplasia in a 15-year-old girl. Note dwarfism of the short limb type, the limbs being disproportionately shorter than the trunk. The limbs are bowed; there is an increase in lumbar lordosis; and the face is small relative to the head.

Figure 8.10 A. Three-month-old infant with achondroplasia. Note the large head, short extremities, and protruding abdomen. B and C. Achondroplasia in a 15-year-old girl. Note dwarfism of the short limb type, the limbs being disproportionately shorter than the trunk. The limbs are bowed; there is an increase in lumbar lordosis; and the face is small relative to the head.

Figure 8.11 Radiograph of a patient with cloverleaf skull characteristic of thanatophoric dwarfism type II. The shape of the skull is due to abnormal growth of the cranial base, caused by a mutation in FGFR-3, followed by craniosynostosis. The sagittal, coronal, and lambdoid sutures are commonly involved.

Human Embryo Limb Buds
Figure 8.12 Development of the limb buds in human embryos. A. At 5 weeks. B. At 6 weeks. C. At 8 weeks. The hindlimb buds are less well developed than those of the forelimbs.

proximal segment by a circular constriction (Fig. 8.12B). Later a second constriction divides the proximal portion into two segments, and the main parts of the extremities can be recognized (Fig. 8.12C). Fingers and toes are formed when cell death in the AER separates this ridge into five parts (Fig. 8.14A). Further formation of the digits depends on their continued outgrowth under the influence of the five segments of ridge ectoderm, condensation of the mes-enchyme to form cartilaginous digital rays, and the death of intervening tissue between the rays (Fig. 8.14, B and C).

Development of the upper and lower limbs is similar except that morphogenesis of the lower limb is approximately 1 to 2 days behind that of the upper limb. Also, during the seventh week of gestation the limbs rotate in opposite directions. The upper limb rotates 90° laterally, so that the extensor muscles lie on the lateral and posterior surface and the thumbs lie laterally, whereas the lower limb rotates approximately 90° medially, placing the extensor muscles on the anterior surface and the big toe medially.

While the external shape is being established, mesenchyme in the buds begins to condense and these cells differentiate into chondrocytes (Fig. 8.13). By the 6th week of development the first hyaline cartilage models, foreshadowing the bones of the extremities, are formed by these chondrocytes (Figs. 8.13 and 8.15). 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.

Ossification of the bones of the extremities, endochondral ossification, begins by the end of the embryonic period. Primary ossification centers are

Mesoderm Mesenchyme Ossification

Figure 8.13 A. Longitudinal section through the limb bud of a mouse embryo, showing a core of mesenchyme covered by a layer of ectoderm that thickens at the distal border of the limb to form the AER. In humans this occurs during the fifth week of development. B. Lower extremity of an early 6-week embryo, illustrating the first hyaline cartilage models. C and D. Complete set of cartilage models at the end of the sixth and the beginning of the eighth week, respectively.

Figure 8.13 A. Longitudinal section through the limb bud of a mouse embryo, showing a core of mesenchyme covered by a layer of ectoderm that thickens at the distal border of the limb to form the AER. In humans this occurs during the fifth week of development. B. Lower extremity of an early 6-week embryo, illustrating the first hyaline cartilage models. C and D. Complete set of cartilage models at the end of the sixth and the beginning of the eighth week, respectively.

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 (Fig. 8.15).

At birth the diaphysis of the bone is usually completely ossified, but the two ends, the epiphyses, are still cartilaginous. Shortly thereafter, however, ossification centers arise in the epiphyses. Temporarily a cartilage plate remains between the diaphyseal and epiphyseal ossification centers. This plate, the

Human Hands Days

Figure 8.14 Scanning electron micrographs of human hands. A. At 48 days. Cell death in the apical ectodermal ridge creates a separate ridge for each digit. B. At 51 days. Cell death in the interdigital spaces produces separation of the digits. C. At 56 days. Digit separation is complete. The finger pads will create patterns for fingerprints.

Figure 8.14 Scanning electron micrographs of human hands. A. At 48 days. Cell death in the apical ectodermal ridge creates a separate ridge for each digit. B. At 51 days. Cell death in the interdigital spaces produces separation of the digits. C. At 56 days. Digit separation is complete. The finger pads will create patterns for fingerprints.

epiphyseal plate, plays an important role in growth in the length of the bones. Endochondral ossification proceeds on both sides of the plate (Fig. 8.15). When the bone has acquired its full length, the epiphyseal plates disappear and the epiphyses unite with the shaft of the bone.

In long bones an epiphyseal plate is found on each extremity; in smaller bones, such as the phalanges, it is found only at one extremity; and in irregular bones, such as the vertebrae, one or more primary centers of ossification and usually several secondary centers are present.

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Responses

  • betty
    What are the shape of the skull in dwarfism?
    6 years ago

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