UNSW Embryology

Musculoskeletal Abnormalities

© Dr Mark Hill (2008)

Acknowledgements

Introduction

There are a large number of different musculoskeletal abnormalities affecting one or a combination of bone and muscle development in the skull, trunk and limbs. This page therefore can only broadly introduce the topic.

Musculoskeletal and limb disorders together form the largest group of congenital defects that occur in Australia. Some defects appear as obvious malformations, such as syndactyly and limb reductions. Other muscular defects only become obvious postnatally when the muscles are required to be used, those in highest use are respiratory (diaphragm, intercostals) and anti-gravity (those that hold you upright) muscles.

Page Links

Abnormalities | Australian Statistics 1981-1992 | Hip Dislocation | Arthrogryposis | Scoliosis |Muscular Dystrophy | Limb Abnormalities | Limb Reduction Defects | Syndactyly | Self Assessment Questions | References | Glossary

Clinical Introduction

1. Normal growth and development of the limb requires (a) normal cell numbers; (b) normal locomotor elements, e.g. bone, joint, muscle; (c) normal blood and nerve supply.

2. Retardation of limb growth is produced by (a) deficient nerve supply; (b) impaired blood supply or (c) systemic abnormalities affecting the growth plate.

3. Increased limb growth is produced by some nerve malformations and by increased blood supply to the growth plate.

(Note: The "figures" referred to below are on posters in the practical laboratory)

Congenital Dislocation of the Hip (CDH)

Introduction (Instability: 1:60 at birth; 1:240 at 1 wk: Dislocation untreated; 1:700).

(a) There is originally a congenital instability of the hip which later dislocates by muscle pulls or gravity if untreated.

(b) There is familial predisposition for this problem and female predominance.

(c) Growth of the femoral head, acetabulum and innominate bone are delayed until the femoral head fits firmly into the acetabulum.

Mechanisms of Production

(a) There is familial displasia of the hip.

(b) There is a relationship between placental transmission of material joint softening hormones (e.g. Relaxin) which are inhibited by androgens in the male foetus. When a and b are present there is instability of the hip.

(c) Dislocation is produced by the small head slipping out of the shallow acetabulum in the extended position of the hip and is inhibited by the abducted position of the hip.

Treatment

Treatment must be instituted early to avoid a growth deformity of the hip. To ensure there is no instability, infants are tested at birth for hip stability and unstable hip children are nursed in the Frog Position (abducted hip posture).

Photo CDH1 Pawich Brace, Photo CDH2 Frog Plaster

Delay in treatment leads to frank dislocation of the hip (the femoral head comes out of joint), and there is a shallow acetabulum and a small femoral head. See Photo CDH3. If this condition is allowed to occur an operation may be necessary to produce a more horizontal roof to the acetabulum and produce hip stability. See Photo CDH4.

Posterior dislocation of the hip produces flexion deformities of the hip with compensatory Lordosis - exaggerated lumbar curvature. See Photo CDH5 (both female).

Questions:

1. In CDH5 the smaller child on the right shows Trendelenberg's Sign - as she raises her right foot the right side of the pelvis lowers instead of raising. In the normal patient the hip rises when the ipsilateral foot is raised from the ground. What muscle is chiefly responsible for the normal tilting of the hip?

2. What conditions may give rise to Trendelenberg's Sign?

OMIM: (1999) Congenital Hip Dislocation | Congenital Hip Dislocation List

Search Pubmed Now: congenital+dislocation+hip[TITL]

Scoliosis

This is involved with assymetric growth impairment of the vertebral bodies.

There is lateral deviation of the spine with a 3-fold deformity:

1. Lateral flexion
2. Forward flexion
3. Rotation of the vertebral column on the long axis

Rotational deformity producing rib hump when the child bends	X-ray of spine

The deformity is compensated by movement of the vertebral column above and below the affected region producing a primary and two secondary curves. This deformity progresses rapidly in adolescence and becomes fixed once bone growth is completed.

Question: Why does the deformity progress rapidly in early adolescence?

OMIM: Scoliosis List

Search Pubmed Now: scoliosis[TITL]

External Links: NIAMS (USA) 2001-Questions and Answers about Scoliosis in Children and Adolescents

Muscular Dystrophies

There are several different types of Muscular Dystrophies (wasting) including: Duchenne Muscular Dystrophy, Autosomal Recessive Muscular Dystrophy, Congenital Muscular Dystrophy and Myotonic Dystrophy.

Duchenne Muscular Dystrophy

The most common occuring in Boys and in Duchenne Muscular Dystrophy (DMD). This cause of the disease was discovered in 1988 as a mutation in dystrophin, a protein that lies under the muscle fiber membrane and maintains the cell's integrity. As skeletal muscles have little prenatal load or use it is not until postnatally that muscle wasting occurs, usually in the anti-gravity muscles first. This is a progressive disease usually detected between 3-5 years old.

There is a milder adult (30-40 years old) onset form of the disease Becker's Muscular Dystrophy (BMD) that involves mutations in the same gene.

The dystrophin gene is very large (one of the biggest) is located on the X chromosome and has several places where mutations have been shown to occur. (More? mutation list)

Links: Genes and Disease- DMD / Muscle Overview | Dystrophin sequence - Plain / Dystrophin sequence - Pretty | OMIM DMD/BMD (about this entry)

Search Pubmed Now: duchenne+muscular+dystrophy[TITL]

Congenital Muscular Dystrophy (CMD)

Mutations in the laminin alpha-2 chain (LAMA2, merosin) gene lead to a deficiency of this protein.

Laminin is an extracellular matrix glycoprotein expressed in basement membranes. The laminin alpha-2 chain is specifically found in basement membranes of striated muscle and Schwann cells.

OMIM: MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT | laminin alpha-2

References:

Hall TE, Bryson-Richardson RJ, Berger S, Jacoby AS, Cole NJ, Hollway GE, Berger J, Currie PD. The zebrafish candyfloss mutant implicates extracellular matrix adhesion failure in laminin {alpha}2-deficient congenital muscular dystrophy. Proc Natl Acad Sci U S A. 2007 Apr 16;

Cohn RD, Mayer U, Saher G, Herrmann R, van der Flier A, Sonnenberg A, Sorokin L, Voit T. Secondary reduction of alpha7B integrin in laminin alpha2 deficient congenital muscular dystrophy supports an additional transmembrane link in skeletal muscle. J Neurol Sci. 1999 Mar 1;163(2):140-52.

Search Pubmed Now: congenital muscular dystrophy[TITL] | laminin alpha chain | merosin

Autosomal Recessive Muscular Dystrophy

Dystroglycan, a protein that associates with both dystrophin and membrane molecules, is a candidate gene for the site of the mutation in autosomal recessive muscular dystrophies. A knockout mouse has been generated that has early developmental abnormalities.

OMIM: dystroglycan

Search Pubmed Now: autosomal+recessive+muscular+dystrophy[TITL]

Myotonic Dystrophy

An inherited disorder in which the muscles contract but have decreasing power to relax. With this condition, the muscles also become weak and waste away. The myotonic dystrophy gene, found on chromosome 19, codes for a protein kinase that is found in skeletal muscle, where it likely plays a regulatory role. The disease is "amplified" through generations probably by a similar GC expansion associated with Huntington disease.

Search Pubmed Now: myotonic+dystrophy[TITL]

Links: Genes and Disease- Myotonic Dystrophy / Muscle Overview | OMIM Myotonic Dystrophy