Musculoskeletal System - Limb Abnormalities: Difference between revisions

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Revision as of 17:14, 25 September 2012

Stage20-23 limbs b.jpg

Introduction

Adult appendicular skeleton

Musculoskeletal and limb abnormalities are one of the largest groups of congenital abnormalities. The upper and lower limbs have a large number of different genetic and environment derived abnormalities, some of which can be surgically repaired, while others may indicate other syndromes or karyotype anomalies (trisomy etc) by association. Many of the hand and foot abnormalities are described as "dactyly" from the Greek (daktulos) for finger or digit.

A 1994 review of data from Hungary (1975-1984)[1] showed in this population an overall 1 in 1,816 prevalence of limb deficiency at birth.

A key historic area of limb abnormalities were those associated with limb reduction (and other defects) with the "morning sickness" prescription drug Thalidomide and its significant teratogenic effects (More? Abnormal Development - Thalidomide).

Musculoskeletal Links: Introduction | mesoderm | somitogenesis | limb | cartilage | bone | bone timeline | bone marrow | shoulder | pelvis | axial skeleton | skull | joint | skeletal muscle | muscle timeline | tendon | diaphragm | Lecture - Musculoskeletal | Lecture Movie | musculoskeletal abnormalities | limb abnormalities | developmental hip dysplasia | cartilage histology | bone histology | Skeletal Muscle Histology | Category:Musculoskeletal
Historic Embryology - Musculoskeletal  
1853 Bone | 1885 Sphenoid | 1902 - Pubo-femoral Region | Spinal Column and Back | Body Segmentation | Cranium | Body Wall, Ribs, and Sternum | Limbs | 1901 - Limbs | 1902 - Arm Development | 1906 Human Embryo Ossification | 1906 Lower limb Nerves and Muscle | 1907 - Muscular System | Skeleton and Limbs | 1908 Vertebra | 1908 Cervical Vertebra | 1909 Mandible | 1910 - Skeleton and Connective Tissues | Muscular System | Coelom and Diaphragm | 1913 Clavicle | 1920 Clavicle | 1921 - External body form | Connective tissues and skeletal | Muscular | Diaphragm | 1929 Rat Somite | 1932 Pelvis | 1940 Synovial Joints | 1943 Human Embryonic, Fetal and Circumnatal Skeleton | 1947 Joints | 1949 Cartilage and Bone | 1957 Chondrification Hands and Feet | 1968 Knee

| Thalidomide


--Mark Hill 09:25, 14 April 2010 (EST) Page Template only - content from original UNSW Embryology site currently being edited and updated.

Some Recent Findings

  • Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications[2] "Both Triphalangeal thumb-polysyndactyly syndrome (TPTPS) and syndactyly type IV (SD4) are due to duplications involving ZPA regulatory sequence (ZRS), the limb-specific Sonic hedgehog (SHH) enhancer. Point mutations in the ZRS and duplications encompassing the ZRS cause distinctive limb phenotypes."
  • A t(4;6)(q12;p23) translocation disrupts a membrane-associated O-acetyl transferase gene (MBOAT1) in a patient with a novel brachydactyly-syndactyly syndrome[3] "One of the genes on chromosome 6, the membrane-associated O-acetyl transferase gene 1 (MBOAT1), was disrupted by the breakpoint. ...Identification of the transferred acyl group and the target may reveal the signaling pathways altered in this novel brachydactyly-syndactyly syndrome."
  • Characterization of a novel ectodermal signaling center regulating Tbx2 and Shh in the vertebrate limb[4] "The data presented here identify the non-AER border of dorsal-ventral ectoderm as a new signaling center in limb development that localizes the ZPA to the limb margin. This finding explains the tight restriction of Shh expression to the posterior margin throughout limb outgrowth as well as the tight restriction of Shh expression to the anterior margin in many mutants exhibiting preaxial polydactyly."

Textbooks

  • The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 15 the skeletal system
  • Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 11 Limb Dev (bone not well covered in this textbook)
  • Before we Are Born (5th ed.) Moore and Persaud Chapter 16,17: p379-397, 399-405
  • Essentials of Human Embryology Larson Chapter 11 p207-228

Developmental Dysplasia of the Hip

X-Ray Developmental Dysplasia of the Hip
Acetabular angle[5]

Also called Congenital Hip Dislocation.

  • Instability: 1:60 at birth; 1:240 at 1 wk: Dislocation untreated; 1:700
  • congenital instability of hip, later dislocates by muscle pulls or gravity
  • familial predisposition female predominance
  • Growth of femoral head, acetabulum and innominate bone are delayed until the femoral head fits firmly into the acetabulum

Barlow test

(Barlow maneuver) A clinical term to describe a physical examination of the newborn for developmental dysplasia of the hip (DDH). The examiner adducts the hip (bringing the thigh towards the midline) while applying light pressure on the knee, directing the force posteriorly. A positive sign is the hip being dislocatable, if the hip can be popped out of socket with this test. This test is then combined with the Ortolani test (maneuver).

The test is named after Thomas Barlow (1845 – 1945) a British royal physician.

Ortolani test

Ortolani maneuver) A clinical term to describe a physical examination of the newborn for developmental dysplasia of the hip (DDH). This is a test for posterior dislocation of the hip. Using the examiner's thumb, abduct the infant's leg, while using the examiner's index finger to place anterior pressure on the greater trochanter. A positive sign is a distinctive 'clunk' which can be heard and felt as the femoral head relocates anteriorly into the acetabulum, usually becomes negative after 2 months of age. This test is combined with the Barlow test (maneuver).

The test is named after Marino Ortolani, the test developer in 1976.

Acetabular index

This clinical measurement is based upon radiograph analysis of the acetabular inclination before ossification of the triradiate cartilage. The index is defined as the angle between Hilgenreiner's line and a line from the inferior margin of the iliac bone through the acetabular bony rim.

Triradiate cartilage is the Y-shaped growth plate region within the hip that does not complete ossification postnatally in humans until 14 - 16 years of age.

X-ray landmarks

  • Hilgenreiner's line - a horizontal line drawn between the two triradiate cartilage centers of the hips, defines a horizontal plane and an approximation to flexion axis of the hips.
  • Perkin's line - a perpendicular line to the horizontal line drawn at the edge of the boney part of the acetabular socket.
  • Shenton's line - an oval that traces the lower pubis contour, that should smoothly continue on to trace the lower edge of the neck of the femur.

Abduction Splints

There is variable evidence for the use of abduction splinting during onset of walking in children on the maturation of mild dysplastic hips.[5]


Links: Screening for developmental dysplasia of the hip: recommendation statement. PMID16510673

Developing Limb Regions

Limb proximodistal developmental regions

The developing limb can be described along the proximodistal axis as having three main regions , with abnormalities along this axis characterised by the changes to these specific skeletal components.

Stylopod

Limb development term describing the proximal region the limb, the skeletal component of the upper limb (forelimb) is the humerus, and for the lower limb (hindlimb) is the femur.

Zeugopod

Limb development term describing the mid-section of the limb , the skeletal components of the upper limb (forelimb) are the radius and ulna, and for the lower limb (hindlimb) are the tibia and fibula.

Autopod

Limb development term describing the distal region the limb, the musculoskeletal component of the upper limb (forelimb) is the hands, and for the lower limb (hindlimb) is the foot.

Limb Abnormality Classification

There have been a number of different classifications applied to limb abnormalities (Classic Classification, Frantz Classification, International Society for Prosthetics and Orthotics (ISPO) Classification System).

The current preferred classification system is the ISPO Classification,[6] which divides all limb deformities into either transverse (no distal remaining portions) or longitudinal (has distal portions).

The original classical classification of limb deficiencies was:

  • Amelia - complete absence of a limb.
  • Meromelia - the partial absence of a limb.
  • Hemimelia - the absence of half a limb.
  • Phocomelia - a flipper-like appendage attached to the trunk. (limbs with a stylopod, a truncated or absent zeugopod, and a nearly intact autopod)
  • Acheiria a missing hand or foot.
  • Adactyly - the absence of metacarpal or metatarsal.
  • Aphalangia - an absent digit, finger or toe.

Hand Abnormality Classification

There is now a international classification for congenital hand anomalies based on an extension of an earlier classification system.[7] Some of these abnormalities can be initially detected prenatally by ultrasound and may be associated with other syndromes or karyotype anomalies.

Groups

I. Failure of formation; transverse (A), or longitudinal (B) (radial and ulnar deficiencies, symbrachydactyly)
II. Failure of differentiation
III. Polydactyly (513 anomalies, Madelung deformity, the Kirner deformity and congenital trigger fingers and trigger thumbs, Triphalangeal thumbs)
IV. Overgrowth
V. Undergrowth
VI. Amniotic band syndrome (amniotic bands)
VII. Generalized skeletal syndromes.
Failure of finger ray induction (cleft hand (IC), central polydactyly (III) and (bony) syndactyly (II)
Unclassifiable


Alignment abnormalities (clenched hand, camptodactyly, clinodactyly, hypokinesia, clubhand, phocomelia), thumb anomalies, abnormal size (macrodactyly, trident hand), abnormal echogenicity (abnormal calcifications), abnormal number (polydactyly, syndactyly, ectrodactyly), and constriction band sequence.

Syndactyly

Syndactyly

Fusion of fingers or toes (Greek, syn = together, dactyly = digit) which may be single or multiple and may affect: skin only, skin and soft tissues or skin, soft tissues and bone. The condition is unimportant in toes but disabling in fingers and requires operative separation and is frequently inherited as an autosomal dominant. The presence of this additional "webbing" reflects preservation of the developmental tissues that in normal development are removed by programmed cell death (apotosis).

Syndactyly occuring in cattle is known as "mulefoot" an autosomal recessive trait and has been associated with mutations in the low density lipoprotein receptor-related protein 4 gene (LRP4). When shortening of the syndactyal digits also occurs it is then described as brachysyndactyly (Greek, brachys = short, syn = together, dactyly = digit). (More? Brachydactyly).

See also an article on molecular control of skeletal size with digit separation.[8]

Links: OMIM - Syndactyly I | Syndactyly II | Syndactyly III | Syndactyly IV | Syndactyly V

Search PubMed Now: Syndactyly | Syndactylia |

Polydactyly

Polydactylia (Image: CDC Imagebank)

Presence of additional toes or fingers (Greek, poly = many, dactyly = digit) also called polydactylia or polydactylism. The condition is often treated surgically in the infant. Polydactyly can also be associated with a number of different syndromes including Greig cephalopolysyndactyly syndrome (GCPS).

There are also several forms of polydactyly including: preaxial polydactyly type-IV (PPD-IV) and postaxial polydactyly.

Preaxial polydactyly (PPD) has been shown as a defect in Sonic Hedgehog (Shh) expression. SHH is normally expressed specifically in the zone of polarizing activity (ZPA) located posteriorly in the limb bud and is expressed in an additional ectopic site (at the anterior margin) in a mouse model of this disorder.

This expression appears to be due to point mutations in the limb-specific regulatory element of the SHH gene.

Six digit cat

The author Ernest Hemmingway in the 1930's had a six-toed cat (Snowball) showing a form of polydactyly and cats with a similar condition today (image) are now called "Hemmingway cats".

Search PubMed Now: Polydactyly | Polydactylia |

Polysyndactyly

Developmental abnormality where there is a combination of additional digits (polydactyly) that are fused together (syndactyly) and is known as polysyndactyly. See also article on treatment of congenital upper extremity problems.[9]

Search PubMed Now: Polysyndactyly

Brachydactyly

Middle phalanges of both hands and feet are very short (Greek, brachys = short, dactyly = digit) in length or absent. Condition can also be associated with endocrine abnormality, pseudohypoparathyroidism (end-organ unresponsiveness to parathyroid hormone) leading to short stature, round facies, brachydactyly, and short fourth or fifth metacarpals.

A chromosomal translocation (t(4;6)(q12;p23) has also been shown to disrupt a membrane-associated O-acetyl transferase gene (MBOAT1) in a patient with a novel brachydactyly-syndactyly syndrome.[10] "One of the genes on chromosome 6, the membrane-associated O-acetyl transferase gene 1 (MBOAT1), was disrupted by the breakpoint. ...Identification of the transferred acyl group and the target may reveal the signaling pathways altered in this novel brachydactyly-syndactyly syndrome."

Search PubMed Now: Brachydactyly

Symbrachydactyly

Symbrachydactyly describes a combination of syndactyly accompanied by brachydactyly. See clinical article on surgical reconstruction in symbrachydactyly using the reverse radial forearm flap.[11]

Search PubMed Now: Symbrachydactyly

Ectrodactyly

Cleft hand apical defect
Ectrodactyly

Ectrodactyly or split hand/foot malformation (SHFM) or cleft hand, central ray deficiency (previously called "lobster-claw malformation"). Abnormality is a deep median cleft of either the hand and/or foot due to the embryonic absence of the central rays.

Highly variable malformation (genetic heterogeneous, 5+ loci mapped) occuring in isolation or in association with other systematic anomalies including congenital heart defects.

During limb development at the time of had or foot formation, the median apical ectodermal ridge (AER) fails to be maintained leading to an absence of its developmental regional signaling. Can have isolated vascular supply related cases and occur as part of a syndrome.


Search PubMed Now: Ectrodactyly | Split hand/foot malformation |

Triphalangeal Thumb (TPT)

Triphalangeal Thumb (Image modified from: Indian Pediatrics)

Developmental abnormality with three phalanges instead of two, forming a long, finger-like thumb.

The isolated triphalangeal thumb anomaly has also been mapped to chromosome region 7q36 and has been identified as caused by point mutations in the ZPA regulatory sequence (ZRS) which is a long-range cis-regulator for the SHH gene.[12]

Search PubMed Now: Triphalangeal Thumb

Links: OMIM - Sall4 | OMIM - Tbx5 | Indian Pediatrics - Indian Pediatrics 2005;42:1246-1247

Talipes Equinovarus

Talipes equinovarus

(Latin, talipes = ankle bone, pes = foot, equinus = horse) Abnormality of the lower limb which begins in the embryonic period (first trimester of pregnancy) resulting in the foot is then turned inward and downward at birth, described as "club foot". Occurs in approximately 1 in 1,000 births, postnatally it affects how children walk on their toes with the foot pointed downward like a horse.

Can also occur in asociation with other syndromes. For example, camptomelic dysplasia, an extremely rare (2 per million live births) lethal congenital bony dysplasia which can be detected by ultrasound (25 weeks) visible as anterior bowing of long bones.

Search PubMed Now: talipes equinovarus

Links: Medline Plus - Clubfoot | The Clubfoot Club |

Amniotic band syndrome (amniotic bands)

Amniotic constriction bands are relatively rare and is caused by damage to the amnion, producing fiber-like bands that trap periperal structures (arms, legs, fingers, or toes) reducing local blood supply leading to abnormal development.

Abnormalities range from a permanent band or indentation around the structure (arm, leg, finger, or toe), digital webbing, too all or part of the limb missing.

Search PubMed Now: Amniotic band syndrome | amniotic bands |

Limb Reduction

Congenital Limb Reduction
X-ray of Limb Reduction

Genetic

There are many different genetic abnormalities and syndromes that have an associated limb reduction.

Trisomy 21 hand

Trisomy 21 - (Down Syndrome) features short and broad hands, clinodactyly (curving of the fifth finger, little finger) with a single flexion crease (20%), hyperextensible finger joints, space between the great toe (big) and the second toe is increased, and acquired hip dislocation (6%).

Diastrophic dysplasia - an autosomal recessive disorder, due to mutations in the DTD sulphate transporter gene (chromosome 5q32–q33). Leads to severe short-limbed dwarfism, progressive spinal and joint problems and can be detected by ultrasound (16 and 19 weeks of gestation).

Environment

Thalidomide was the most celebrated limb reducing insult (teratogen) in humans which also produced a range of other deformities depending on developmental time and concentration of the drug exposure.

Many additional substances (teratogens) have been found capable of producing limb reduction defects in experimental animals but few have been related to humans.

Limb reduction defects may also be either direct or indirect, for example with loss of blood supply to part of the limb or abnormal innervation at the spinal or cerebral level. There are a number of as yet undefined mechanisms involved.

Limb reduction defects may be apical (congenital amputation) or pre- or post-axial (absence of radius and lateral digits; ulnar and medial digits).

Questions:

What area is missing in the reduced limb shown above?

What will be the relative growth rates of the right and left humeri in this child?

Search PubMed Now: Congenital Limb Reduction | Thalidomide

Links: Abnormal Development - Thalidomide | The Swedish Thalidomide Society

Nail Abnormalities

Covered in developmental notes on [skin2.htm Integumentary Development Abnormalities], [skin12.htm Nail Development] and [skin.htm Integumentary Development].

Congenital hyponychia

Anonychia

Nail-patella syndrome

Ectodermal dysplasias

Brachydactylies

Search PubMed Now: Congenital hyponychia | Anonychia

References

  1. <pubmed>8172251</pubmed>
  2. <pubmed>18417549</pubmed>
  3. <pubmed>17440500</pubmed>
  4. <pubmed>17300775</pubmed>
  5. 5.0 5.1 <pubmed>15958160</pubmed>| BMC Pediatr.
  6. <pubmed>1923724</pubmed>
  7. <pubmed>12416642</pubmed>
  8. <pubmed>17360777</pubmed>
  9. <pubmed>17415231</pubmed>
  10. <pubmed>17440500</pubmed>
  11. <pubmed>17275589</pubmed>
  12. <pubmed>18417549</pubmed>


Reviews

<pubmed>17661738</pubmed>

Articles

<pubmed></pubmed> <pubmed></pubmed> <pubmed>22379552</pubmed>| PMC3288491 <pubmed>17440500</pubmed> <pubmed>17275589</pubmed> <pubmed>17300775</pubmed> <pubmed>16676441</pubmed> <pubmed>1923724</pubmed> <pubmed>3618097</pubmed> <pubmed>8172251</pubmed>

Search PubMed

Search Pubmed: limb developmental abnormalities

Additional Images

Terms

  • preaxial - referring to the lateral (radial) aspect of the upper limb, and the medial (tibial) aspect of the lower limb.
  • postaxial - referring to the medial ( ulnar) aspect of the upper limb, and the lateral (fibular) aspect of the lower limb.


Glossary Links

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Cite this page: Hill, M.A. (2024, March 29) Embryology Musculoskeletal System - Limb Abnormalities. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Limb_Abnormalities

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G