Musculoskeletal System - Abnormalities

Embryology - 11 Dec 2023        Expand to Translate
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Introduction

Congenital dislocation hip

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 and link to other resources with more specific information.

Musculoskeletal and limb disorders together form the largest group of congenital defects that occur in Australia. The three most commonly occurring are developmental dysplasia of the hip, cleft palate, cleft lip and palate.

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.

International Classification Diseases - Musculoskeletal

System Abnormalities

Abnormality Links: abnormal development | abnormal genetic | abnormal environmental | Unknown | teratogens | ectopic pregnancy | cardiovascular abnormalities | coelom abnormalities | endocrine abnormalities | gastrointestinal abnormalities | genital abnormalities | head abnormalities | integumentary abnormalities | musculoskeletal abnormalities | limb abnormalities | neural abnormalities | neural crest abnormalities | placenta abnormalities | renal abnormalities | respiratory abnormalities | hearing abnormalities | vision abnormalities | twinning | Developmental Origins of Health and Disease |  ICD-11 Historic Embryology   1915 Congenital Cardiac Disease | 1917 Frequency of Anomalies in Human Embryos | 1920 Hydatiform Degeneration Tubal Pregnancy | 1921 Anencephalic Embryo | 1921 Rat and Man | 1966 Congenital Malformations

Some Recent Findings

Mutations in INPP5K cause a form of congenital muscular dystrophy overlapping Marinesco-Sjögren syndrome and dystroglycanopathy "Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome. Whole-exome sequencing revealed homozygous missense and compound heterozygous mutations in INPP5K in the affected members of each family. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle."

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Congenital Musculoskeletal Abnormalities | Hip Displasia | Scoliosis | Duchenne Muscular Dystrophy | Muscular Dystrophy | Calcaneovalgus

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. The incidence of common orthopaedic problems in newborn at Siriraj Hospital "A prospective study was conducted by physical examination of 3,396 newborns from June 2009 to September 2009. Incidence of calcaneovalgus was found in 60:1,000 live births following by metatarsus adductus in 7.6:1,000, polydactyly or syndactyly in 2.6:1,000, talipes equninovarus in 2.4:1,000, brachial plexus injury in 1.5:1,000, developmental dysplasia of hip in 0.6:1,000, osteogenesis imperfecta in 0.6:1,000, skeketal dysplasia in 0.6:1,000, congenital vertical talus in 0.3: 1,000 and fracture clavicle at birth in 0.3: 1,000. In the present study, the calcaneovalgus (flexible flatfoot) was the most common orthopaedic problem followed by metatasus adductus, polydactyly or syndactyly." Delayed bone age due to a dual effect of FGFR3 mutation in Achondroplasia. "All these data provide evidence that FGFR3 regulates normal chondrocyte proliferation and differentiation during bone growth and suggest that constitutive activation of the receptor disrupts both processes. Therefore, the consequences of FGFR3 activation on the physiological process of bone development appear to be dependent on spatial and temporal occurrence."

Australian Statistics

The ten most frequently reported birth defects in Victoria between 2003-2004.

1. Hypospadias
2. Obstructive Defects of the Renal Pelvis or Obstructive Genitourinary Defects
3. Ventricular Septal Defect
4. Congenital Dislocated Hip
5. Trisomy 21 or Down syndrome
6. Hydrocephalus
7. Cleft Palate
8. Trisomy 18 or Edward Syndrome - multiple abnormalities of the heart, diaphragm, lungs, kidneys, ureters and palate 86% discontinued.
9. Renal Agenesis/Dysgenesis - reduction in neonatal death and stillbirth since 1993 may be due to the more severe cases being identified in utero and being represented amongst the increased proportion of terminations (approximately 31%).
10. Cleft Lip and Palate - occur with another defect in 33.7% of cases.

Developmental Dysplasia of the Hip

X-Ray Developmental Dysplasia of the Hip

Acetabular angle

ICD-11 LB74.0 Developmental dysplasia of hip A condition caused by failure of the hip to correctly develop during the antenatal period. This condition is characterized by slippage of the hip from the socket. This condition may present with outward turning of the leg, reduced movement on one side of the body, shortness of one leg, uneven skin folds on thigh or buttocks, walking difficulties, or inward rounding of the lower back.

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.

Links: Developmental dysplasia of the hip

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 manoeuvre) 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 (manoeuvre). Named after Marino Ortolani, the test developer in 1976.

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.

Scoliosis

Historic image scoliosis (Braune 1877)

Scoliometry

ICD-11 FA70 Spinal deformities - FA70.1 Scoliosis Scoliosis is known not to be limited only to the frontal plane, and can be defined as a three dimensional torsional deformity of the spine and trunk it causes a lateral curvature in the frontal plane, an axial rotation in the horizontal one, and a disturbance of the sagittal plane normal curvatures, kyphosis and lordosis, usually, but not always, reducing them in direction of a flat back. “Structural scoliosis”, or just scoliosis, must be differentiated from “functional scoliosis”, that is a spinal curvature secondary to known extraspinal causes (e.g. shortening of a lower limb or paraspinal muscle tone asymmetry). It is usually partially reduced or completely subsides after the underlying cause is eliminated (e.g. in a recumbent position).  ICD-11 See also - LB73.25 Congenital scoliosis due to congenital bony malformation | FC01.5 Postradiation scoliosis FC01 Postprocedural disorders of the musculoskeletal system

frequency of congenital scoliosis is approximately 0.5, or 1 in 1,000 births. assymetric growth impairment of vertebral bodies lateral deviation of spine (Lateral flexion, Forward flexion, Rotation of vertebral column on long axis) compensated by movement of vertebral column above and below affected region (producing a primary and two secondary curves) progresses rapidly in adolescence and becomes fixed once bone growth is completed. 10 degree curvature demonstrated by upright spine roentgenograms by the Cobb method both genetic and environmental terartogens implicated. a large number of chromosomal deletions relating to regions 2p13 – 15, 6q13 and 15q12 have been identified.

Chêneau's Brace

Chêneau Brace

Dr. Chêneau fabricated the original "Chêneau Brace" in 1979 and is commonly used for the treatment of scoliosis and thoracic hypokyphosis in some European countries, though not commonly in either North America or the United Kingdom. The brace corrects by a system of multipoint pressure zones and expansion chambers.

Harrington Rod

Dr Paul Harrington, a USA orthopaedic surgeon, in 1953 designed the "Harrington implant", the first modern spinal instrumentation system that produced both correction and immobilization. This historic system has now been replaced by more modern systems.

Links: axial skeleton

Scoliosis Research Society Questionnaires

The Scoliosis Research Society has a number of Patient Outcome Questionnaires available. The questionnaires relating to lumbar surgery are the SRS22R preoperative and the SRS30 one-year postoperative.

For idiopathic scoliosis, the generic quality of life measurement quantified by SRS22R has been shown to be overall similar between males and females in treatment and age groups, but reduced in comparison with the general population.

Links: Scoliosis Research Society - Patient Outcome Questionnaires online SRS22R calculator

Muscular Dystrophy

ICD-11
8C70 Muscular dystrophy 8C70.0 Becker muscular dystrophy 8C70.1 Duchenne muscular dystrophy 8C70.2 Emery-Dreifuss muscular dystrophy 8C70.3 Facioscapulohumeral muscular dystrophy 8C70.4 Limb-girdle muscular dystrophy 8C70.5 Scapuloperoneal muscular dystrophy 8C70.6 Congenital muscular dystrophy

There can be abnormalities associated directly with muscle differentiation and function as well as those mediated indirectly by abnormalities of innervation or skeletal development and other associated systems.

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.

• X-linked dystrophy
• large gene encoding cytoskeletal protein - Dystrophin
• progressive wasting of muscle, die late teens

Becker Muscular Dystrophy

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

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.

Myotonic Dystrophy

ICD-11 8C71.0 Myotonic dystrophy Myotonic dystrophy is a group of inherited muscular disorders. It is the most common form of muscular dystrophy that begins in adulthood. Myotonic dystrophy is characterized by progressive muscle wasting and weakness, and prolonged muscle contractions (myotonia) that are not able to relax after use. Other signs and symptoms of myotonic dystrophy include slurred speech or temporary locking of their jaw, cataracts and cardiac conduction defects. In affected men, hormonal changes may lead to early balding and infertility. The clinical severity varies widely among affected patients, even among members of the same family.

Myotonic dystrophy (DM) is the most common inherited, autosomal dominant neuromuscular disorder in adults, affecting 1 out of 8000 people. The disease causes myotonia and muscle weakness in skeletal muscles with a risk of life-threatening cardiorespiratory disorders. The disease is "amplified" through generations probably by a similar GC expansion associated with Huntington disease.

Two genetic types:

1. DM1 - expansion of cytosine thymidine guanine (CTG) repeats in non-coding regions (3′-untranslated region) of the myotonic dystrophy protein kinase (DMPK) gene.
2. DM2 - expansion of CCTG repeats in zinc finger protein 9 (ZnF9) gene.

Facioscapulohumeral Muscular Dystrophy

(FSHD) This form of muscular dystrophy is an autosomal dominant genetic disorder characterized by progressive muscle weakness and wasting that typically begins in the face, shoulder-girdle and upper arm. Currently thought to relate to an impaired muscle regeneration process.

Links: skeletal muscle

Spinal Muscular Atrophy

ICD-11 8B61 Spinal muscular atrophy (ICD-10-CM Diagnosis Code G12.9)

Spinal muscular atrophy (SMA) is a rare neural genetic condition that leads to a loss of motor neurons and then progressive muscle wasting. The disease exists in several different forms: Type 1, Type 2, and Type 3a SMA. A new drug treatment using nusinersen (trade name Spinraza®) has led to the inclusion of SMA in the newborn heel-prick test (Guthrie test).

Links: spinal cord

Congenital Myasthenic Syndromes

ICD-11

Myasthenia gravis or certain specified neuromuscular junction disorders Myasthenia gravis is the most common autoimmune disease affecting the neuromuscular junction and is characterised by painless fatigable muscle weakness. It is caused by autoantibodies against neuromuscular junction proteins, either the nicotinic acetylcholine receptor (AChR) or the muscle specific tyrosine kinase (MuSK). Mutations in neuromuscular junction proteins cause congenital myasthenic syndromes. Other antibodies mediated conditions affecting the neuromuscular junction, including Lambert Eaton myasthenic syndrome and neuromyotonia."

A heterogeneous group of neuromuscular disorders (32 gene mutations, autosomal dominant or autosomal recessive) that have an impairment of neuromuscular transmission. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1.

• 8 presynaptic proteins
• 4 synaptic proteins
• 15 post-synaptic proteins
• 5 glycosilation proteins

Limb Abnormalities

Genetic

• Human Gene Mutations - mutation of any of the patterning genes will result in limb abnormalities (Will put Table on Web page mutations and terminology)

Type II syndactyly- HoxD13

Maternal

• thalidomide Phocomelia
• short ill-formed upper or lower limbs
• hyperthermia

Links: limb abnormalities | thalidomide

Syndactyly

Syndactyly

Fusion of fingers or toes 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).

Polydactyly

Polydactylia

Presence of additional toes or fingers also called polydactylia or polydactylism. The condition is often treated surgically in the infant.

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

(More? Limb Development Abnormalities - Polydactyly)

Polysyndactyly

Developmental abnormality where there is a combination of polydactyly with syndactyly is known as polysyndactyly.

Triphalangeal Thumb (TPT)

ICD-11 Structural developmental anomalies of the skeleton - LB76 Triphalangeal thumb | LD26.2 Syndromes with limb duplication, polydactyly, syndactyly or triphalangism

Triphalangeal thumb Developmental abnormality with three phalanges instead of two, forming a long, finger-like thumb. Usually inherited as an autosomal dominant trait, gene locus chromosome region 7q36.

Calcaneovalgus

ICD-11 LB98.2 Congenital valgus deformities of feet - LB98.22 Talipes calcaneovalgus

• Occurs in about 5% of all newborns.
• Females are affected more often than males.
• Deformity can be unilateral or bilateral.
  • external rotation of the calcaneus.
  • an overstretched Achilles tendon.
  • tight anterior leg musculature.

See the review "The Newborn Foot" (2004).

Gastroschisis

ICD-11 Structural developmental anomalies of the diaphragm, abdominal wall or umbilical cord - LB02 Gastroschisis

By definition, it is a body wall musculoskeletal defect, not a gastrointestinal tract defect, which in turn impacts upon GIT development.

Gastroschisis (paraomphalocele, laparoschisis, abdominoschisis, abdominal hernia) is an abdominal wall defect associated with evisceration of the intestine (2.5 cases/10,000 births), occuring more frequently in young mothers (less than 20 years old). There have been reports that this abnormality is increasing in incidence. The abnormality is usually situated to the right of the umbilicus and abdominal contents, mainly gastrointestinal, are found outside the anterior body wall.
Can occur in isolation and also in association with other gastrointestinal anomalies (intestinal atresia, perforation, necrosis or volvulus). Defects in other organ systems have been reported in up to 35% of children. There are several theories as to the cause of this abdominal wall defect, including recently failure of the yolk sac and related vitelline structures to be incorporated into the umbilical stalk. The condition can often be detected by ultrasound scan. Reported as a high mortality defect, only 60% of children survive until the end of the first year of age.
Gastroschisis patients are commonly small for gestational age (SGA, birth weight < 10th centile). Frequency line graphs of the birth weight distribution, Kolmogorov-Smirnov test confirmed that this difference was significant (p < 0.001). black line - gastroschisis cases gray line - controls

Gastroschisis Classification

There has been a recent attempt to classify gastroschisis in order to measure clinical outcomes.

• Simple gastroschisis - intact continuous bowel that is not compromised or breached at delivery or presentation
• Complex gastroschisis - presence of one or more of intestinal atresia, perforation or intestinal necrosis at delivery or presentation, or missed atresia

Links: gastroschisis | Ultrasound movie - Gastroschisis | UCSF Childrens Hospital - Gastroschisis | Brown University Image Bank- Abdominal Wall Defects

Inguinal Hernia

Inguinal hernias are more common in males and associated with the fetal/neonatal developmental descent of the testis through the abdominal wall. The following graphs are from a study of Danish data on postnatal hernia repairs. In contrast, femoral hernia repairs occur mainly in adults in both sexes and increases with age.

Inguinal hernia repair	Femoral hernia repair

Links: genital abnormalities

References

Journals

• Scoliosis - the official journal of the Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT) and affiliated with the International Research Society of Spinal Deformities (IRSSD), is ready to receive manuscripts on all aspects of the prevention, control, and treatment of scoliosis and other spinal deformities.
• BMC Musculoskeletal Disorders is an open access journal publishing original peer-reviewed research articles in all aspects of the prevention, diagnosis and management of musculoskeletal and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.

Reviews

Perronnet C & Vaillend C. (2010). Dystrophins, utrophins, and associated scaffolding complexes: role in mammalian brain and implications for therapeutic strategies. J. Biomed. Biotechnol. , 2010, 849426. PMID: 20625423 DOI.

Le Rumeur E, Winder SJ & Hubert JF. (2010). Dystrophin: more than just the sum of its parts. Biochim. Biophys. Acta , 1804, 1713-22. PMID: 20472103 DOI.

Lapidos KA, Kakkar R & McNally EM. (2004). The dystrophin glycoprotein complex: signaling strength and integrity for the sarcolemma. Circ. Res. , 94, 1023-31. PMID: 15117830 DOI.

Gore AI & Spencer JP. (2004). The newborn foot. Am Fam Physician , 69, 865-72. PMID: 14989573

Articles

Singh SM, Kongari N, Cabello-Villegas J & Mallela KM. (2010). Missense mutations in dystrophin that trigger muscular dystrophy decrease protein stability and lead to cross-beta aggregates. Proc. Natl. Acad. Sci. U.S.A. , 107, 15069-74. PMID: 20696926 DOI.

Norwood FL, Sutherland-Smith AJ, Keep NH & Kendrick-Jones J. (2000). The structure of the N-terminal actin-binding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy. Structure , 8, 481-91. PMID: 10801490

Search PubMed

Search April 2010

• Musculoskeletal System Development - All (44637) Review (5065) Free Full Text (6601)
• Musculoskeletal Development - All (44637) Review (5065) Free Full Text (6601)

Search Pubmed: musculoskeletal system abnormalities

Additional Images

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  Adult axial skeleton

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  Adult appendicular skeleton

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  Bone structure

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  Developing vertebra

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  Endochondral bone

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  Fetal head lateral (12 weeks)

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  Fetal head medial (12 weeks)

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  Fetal head section (12 weeks)

Terms

• centrum - (vertebral body) anatomical term referring to the main bony part of the vertebra that forms the majority of the axial skeleton.

• Cobb angle - clinical method of measuring the degree of scoliosis and post-traumatic kyphosis. Named after the American orthopedic surgeon John Robert Cobb (1903 - 1967) an American orthopedic surgeon.

• haemal arch - referring to the bony arch region within animal tail vertebra that contains blood vessels.

• idiopathic scoliosis - clinical term for a spinal column deformity appearing usually postnatally after the age of 10 years old.

• lordosis - clinical and anatomy term describing the curvature of the spine with the convexity toward the front. Normal to have lordosis in the cervical and lumbar regions of the spinal column.

• neural arch - referring to the bony arch region within vertebra that contains the spinal cord.

• notochord sheath - region surrounding the notochord. in teleost fish direct mineralization of this region, by intramembranous ossification, forms the initial vertebral centrum. (More? zebrafish)

• rib hump - clinical term for the prominence formed by ribs on the convexity of a curve, caused by rotation of the spine and attached ribs.

• spinal column - term referring to the musculoskeletal elements (vertebrae, ligaments, and intervertebral discs), that surround the spinal cord and form the axial skeleton.

• Spondylometaphyseal dysplasia - (SMD) rare form of bone dysplasia comprising various types of chondrodystrophy characterized by metaphyseal irregularities of the long bones, together with generalized platyspondyly of varying severity in the spine. First described in 1967 by Kozlowski. {More? image)

• synsacrum - in birds sacral and lumbar vertebrae fused region forming elongated sacral region.

• thoracic hypokyphosis - term referring to the backward curve in the upper spine is to great, round back, Scheuermann's disease, or simply kyphosis.

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

• Scoliosis - the official journal of the Society on Scoliosis Orthopaedic and Rehabilitation Treatment (SOSORT) and affiliated with the International Research Society of Spinal Deformities (IRSSD).

• Young Women's Health - scoliosis

• Scoliosis Australia

• nScoliosis - online srs-22 calculator

Glossary Links

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Cite this page: Hill, M.A. (2023, December 11) Embryology Musculoskeletal System - Abnormalities. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Abnormalities

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© Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G