This document provides an overview of congenital bone and joint diseases. It begins with an introduction and outline. The first section discusses genetic aspects, including basic genetic principles like chromosomes, genes, alleles, and patterns of inheritance. It describes numerical and structural chromosomal abnormalities. The second section covers bone dysplasias, including classification systems and a simplified classification covering disorders like dwarfism and abnormalities around the growth plate.

1. Congenital Bone & joint Diseases By Dr.Abdullah bin Habeeballah bin Abdullah Juma F.R.C.S.Ed Associate Professor & Consultant Orthopaedic Surgeon

2. Introduction 1. Genetic aspects of orthopaedics . 2. Bone Dysplasias. 3. Neuromuscular Diseases. 4. The Spine. 5. The Hip. 6. The Knee. 7. The Foot.

3. Continue……… 8. Other Anomalies in the Extremities . 9. The Congenital Amputee . 10.Torsional deformities . 11.Juvenile Chronic Arthritis. 12.Bleeding Disorders. 13.Miscellaneous Conditions.

4. 1. Genetic Aspects of Orthopaedics Abnormalities of skeletal development can be of unknown aetiology , or attributed to genetic abnormality due to structural changes in the chromosomes . The basic genetic principles are important to understand and apply clinically. These are the guide lines for these complex clinical conditions.

5. Basic genetic principles : Chromosomes aggregate to form nucleus. Chromosomes can be seen individually during cell division by a special staining . Normal no. of chromosomes is 46 (Diploid no.) including sex chromosomes (X & Y). No. of chromosomes at cell division is 23 (Haploid no.) and form gametes, 22 pairs are autosomes & 1 pair is sex type.

6. Each chromosome consists of DNA molecules embedded in protein matrix. Each DNA molecule consists of groups of polypeptide chains of a double helix . Each group of polypeptide chains form a gene . The corresponding gene at the opposite locus of the paired chromosome is known as an allele .

7. If the members of a pair of alleles are identical , the person is known as Homozygous , and if different then he is Heterozygous. Chromosomal abnormalities can be numerical and structural. Numerical abnormalities occur due to changes in no. of chromosomes due to failure of paired chromosomes to separate at the anaphase of cell division.

8. Numerical abnormalities of multiples of haploid no. of gametes produce polypoid cells , e.g. trisomy ( of 21 in Down’s syndrome) .

9. Structural Abnormalities occur during disjunction and recombination due to breakage or deletion of part of a chromosome or translocation. ( Translocation arise when the position of a portion of a chromosome becomes changed & doesn't recombine opposite it’s homologue,e.g. Cri du chat syndrome ) .

10. Structural changes are caused by : Normal event . Irradiation . Virus infection . Late maternal age . Other agents .

11. In the genetic aspects of orthopaedics , the pattern of inheritance is clinically recognizable as an expression of the phenotype and known as penetrance . The degree of phenotypic presentation is called expression of the gene .

12. Genetic Aspects A. A single gene disorder . B. A multi-factorial disorder .

13. A. Single Gene Disorders Due to a single abnormal gene . This is the largest group of orthopaedic anomalies with a known genetic basis. Classification : can be Dominant or Recessive according to the pattern of inheritance .

14. Classification of single gene disorders Dominant : the abnormal single gene is expressed whether it is homozygous or heterozygous. This can be either Autosomal or X – linked . Recessive : the abnormal single gene is expressed only when homozygous. This can be either Autosomal or X-linked.

15. Autosomal Dominant Inheritance Male & Female are equally affected. The chance of producing affected progeny is 50% in a mating between an affected and non-affected person . Unaffected offspring will not inherit the abnormal gene .

16. Autosomal Recessive Inheritance The abnormal gene comes from both parents , although they are clinically normal . The carrier is in a state of heterozygous. The chance of 2 parents being heterozygous for such abnormal gene is greater if they have a common ancestry such as consanguineous marriages . Their offspring will be ; ¼ diseased ( homozygous ) , 2/4 carrier ( heterozygous ) & ¼ normal .

17. X-linked Dominant Inheritance Very rare . The affected father transmits the disease to all his daughters & none to his sons . The affected mother pass trait to ½ of her daughters & ½ of her sons . Example : Vit.D Resistant Rickets .

18. X-linked Recessive Inheritance The abnormal recessive gene is carried on X chromosome & will be expressed in the presence of a Y chromosome (Hemizygous ) . Hence male is diseased & female is a carrier .

19. An affected male will transmit a Y chromosome to his sons & therefore will not be affected and X chromosome to his daughters & therefore will be carriers. If affected male marry a carrier female then ½ of their daughters will be affected (Hemizygous) & ½ of daughters will be carriers .

20. Genetic Aspects A. A single gene disorder . B. A multi-factorial disorder .

21. B. Multi-factorial Inheritance Some orthopaedic conditions have a familial predisposition BUT no clear inheritance . Hence , both genetic & environmental factors combine to present those anomalies . Examples : Spina Bifida & anencephaly , C.T.E.V. , Perthes’ Disease and A.I.S.

22. Spina Bifida & Anencephaly The risk of recurrence after the 1 st affected child is ; 3 - 6 % The risk of recurrence after the 2 nd affected child is ; 10 %

23. Congenital Talipes Equino-Varus deformity (C.T.E.V.) The risk of recurrence after the 1 st affected child is ; < 5 % The risk of recurrence after the 2 nd affected child or one parent affected is; 20 %

24. Legg-Calve-Perthes’ Disease The risk factors are : Low socio-economical class . Children born 3d or later . Elder parents . Fetal mal-position .

25. Adolescent Idiopathic Scoliosis (A.I.S. ) This type of spinal abnormality occurs in the coronal plane of the spine . It appears in the adolescent phase and more commoner in female . No identifiable cause , but it shows a strong familial tendency .

26. Introduction 1. Genetic aspects of orthopaedics . 2. Bone Dysplasias . 3. Neuromuscular Diseases. 4. The Spine. 5. The Hip. 6. The Knee. 7. The Foot.

27. 2. Bone Dysplasias Uncommon . 2 types : Generalized ( Dysplasias ) & Localized ( Dysostosis ) . Growth disturbance can be in the Epiphysis , Metaphysis or Vertebrae . Dwarfism is a pathological diminution of height below the normal range of population .

28. Investigations & Diagnosis of Bone Dysplasias Clinical Examination for deformity , disproportion , height , span , eye & ear exam , I.Q. Radiological Examination of skull (always) & skeletal survey . Biochemical investigations such as urinalysis as in Mucopolysaccharidoses .

29. Family study of pedigree & pattern of inheritance . Other investigations such as histology , histochemical study , amniocentesis at 16/52 weeks , foetoscopy , endoscopy , level of alpha-fetoprotein and ultrasound .

30. Classification of Bone Dysplasias Authors who contributed in classification of bone Dysplasias : Sir Thomas Fairbank “ An Atlas of General Affections of the Skeleton” Weiderman & Langer .. Germany Lammy & Maroteaux .. France McKusick .. USA Waynne – Davies .. UK

31. Rubin 1964 , wrote “ Dynamic Classification of Bone Dysplasias ” based on the anatomical site of the abnormality: epiphysis , growth plate , metaphysis , or diaphysis . European Society of Paediatric Radiology in Paris ,1969,publishing “ International Nomenclature of Constitutional Disorders of Bone “ 1970 .

32. F.T.Horan wrote , a simple classification in the Postgraduate Textbook of Clinical Orthopaedics . This classification was simplified for the sake of description and understanding , but the subject is so complex that needs continuous updating and revision .

33. A simple Classification of Bone Dysplasias 1. Dwarfism . 2. Disorders around growth plate ; a. Predominantly epiphyseal b. Predominantly metaphysial c. Predominantly vertebrae

34. Continue…Classification of Bone Dysplasia 3. Changes in bone density ; increased vs. decreased 4. Craniotubular disorders . 5. Craniofacial abnormalities . 6. Vertebral anomalies . 7. Lysosomal storage disorders . 8. Abnormalities of cartilage & fibrous tissues . 9. Miscellaneous disorders .

35. A simple Classification of Bone Dysplasias 1. Dwarfism . 2. Disorders around growth plate ; a. Predominantly epiphyseal b. Predominantly metaphysial c. Predominantly vertebrae

36. 1. Dwarfism : 2 types Proportionate : There is equal involvement of all bony segments . The patient presents with a short stature in a miniature scale as seen in the circus . Disproportionate : This is of 2 types ; 1. Short limb Dwarf 2. Short trunk Dwarf Both types show atypical phenotypes and clinically obvious as atypical dwarf .

37. A simple Classification of Bone Dysplasias 1. Dwarfism . 2. Disorders around growth plate ; a. Predominantly epiphyseal b. Predominantly metaphysial c. Predominantly vertebrae

38. 2. Disorders around the growth plate : 3 groups A. The epiphyseal side of the growth plate is principally involved leading to failure to produce a normal ossific nucleus . B. The metaphysial side of the growth plate is principally involved leading to failure of endochondral bone formation . C. The vertebral growth is mainly involved in association with abnormality of epiphysis or metaphysis .

39. A simple Classification of Bone Dysplasias 1. Dwarfism . 2. Disorders around growth plate ; a. Predominantly epiphyseal b. Predominantly metaphysial c. Predominantly vertebrae

40. A. Predominantly Epiphyseal Involvement : Multiple Epiphyseal Dysplasia( MED ) : Autosomal Dominant . Most forms give little problems . Symptoms arise from premature degenerative changes in the weight bearing joints in adults .

41. 2. Chondrodysplasia Punctata ( Stippled Epiphysis ) : Autosomal dominant . Severe form is autosomal recessive . 2 main forms ; * a. Majority have flat face , depressed nasal bridge , atrophic skin , cataracts , joint contractures , scoliosis , asymmetrical limb shortening & stippling of epiphysis of long bones up to the age of 4 . * b. Conradi – Hunnermann . The affected infant is stillborn .

42. NOTE : Stippling of epiphysis can occur in ; Multiple Epiphyseal Dysplasia . Spondylo – Epiphyseal Dysplasia . Hypothyroidism . Fetal Warfarin Syndrome .

43. A simple Classification of Bone Dysplasias 1. Dwarfism . 2. Disorders around growth plate : a. Predominantly epiphyseal b. Predominantly metaphysial c. Predominantly vertebrae

44. B. Predominantly Metaphyseal Involvement : 1. Achondroplasia . 2. Hypochondroplasia . 3. Metaphyseal Chondroplasia . 4. Familial Hypophosphataemia ( Vitamin D – Resistant Rickets )

45. 1. A chondroplasia 80% result from new mutation . Autosomal dominant . Commonest form of dwarfism . Disproportionate type of dwarfism . Short – limb dwarf & proximal segments are particularly affected . Apparent at birth .

46. Metaphyseal abnormalities predominate . Some spinal involvement . Forehead prominent . Nasal bridge depressed . Fingers are short & stubby with a trident appearance . Walk late .

47. Prominent abdomen . Hip flexion contracture . Genu varus deformity late in childhood . Valgus deformity of the ankle joint . Lumbar lordosis . Mid spinal kyphosis in infancy & disappears after walking .

48. X –Rays : Calvarium is large . Base of skull is underdeveloped . Limbs are short , wide , irregular metaphyses but epiphyses are normal . Pelvis shows squared iliac wings & small greater sciatic notches .

49. Narrow spinal canal . Pedicles are short & inter – pedicular space is reduced . Surgery will be required to correct deformities and decompress the spine if symptoms arise . Family counseling is needed .

50. B. Predominantly Metaphyseal Involvement : 1. Achondroplasia . 2. Hypochondroplasia . 3. Metaphyseal Chondroplasia . 4. Familial Hypophosphataemia ( Vitamin D – Resistant Rickets )

51. 2. Hypochondroplasia Autosomal dominant . Distinct genetically from achondroplasia . The cranium,facies & fingers are normal . Stature less stunted . Spinal changes are less . Clinical stigmata are minimal & not easily diagnosed .

52. X –Rays : . Pelvis shows horizontal sacrum & short femoral necks .

53. B. Predominantly Metaphyseal Involvement : 1. Achondroplasia . 2. Hypochondroplasia . 3. Metaphyseal Chondroplasia . 4. Familial Hypophosphataemia ( Vitamin D – Resistant Rickets )

54. 3. Metaphyseal Chondrodysplasia Autosomal dominant . Types : Schmid , Jansen & McKusick (Cartilage Hair Hypoplsia) . Schmid type ( commonest ) ; Short stature . Bow legs . Bilateral Coxa Vara . Lordotic lumbar spine .

55. B. Predominantly Metaphyseal Involvement : 1. Achondroplasia . 2. Hypochondroplasia . 3. Metaphyseal Chondroplasia . 4. Familial Hypophosphataemia ( Vitamin D – Resistant Rickets )

56. 4. Familial Hypophosphataemia ( Vitamin-D Resistant Rickets ) X-linked dominant trait . Metabolic disease . Deformity of lower limbs ; Bow legs . Knock knees . Windswept deformity . Skeletal deformities are progressive .

57. X – Rays : . Wide irregular metaphysis . . Normal epiphysis . . Osteoporosis . . Pseudo -fractures .

58. A simple Classification of Bone Dysplasias 1. Dwarfism . 2. Disorders around growth plate : A. Predominantly epiphyseal B. Predominantly metaphysial C. Predominantly vertebrae

59. C. Predominantly Vertebrae 1. Spondylo – Epiphyseal Dysplasia . 2. Pseudo – Achondroplasia . 3. Diastrophic Dysplasia . 4. Rare Syndromes .

60. 1. Spondylo – Epiphyseal Dysplsia.. 2 forms : Congenita ; Autosomal dominant At birth Short-trunk dwarf Barrel chest G.valgus&varus def. Club foot Cleft palate Tarda ; X-linked recessive Less severe ,variable Apparent later Relative short trunk Early O.A. of joints Mild club foot No cleft palate

61. X – Rays : Epiphyses late Vertebral bodies flat (platyspondyly) Odontoid process hypoplastic leading to atlanto-axial instability X –Rays : Mild dysplastic changes in the joints Platyspondyly with a hump in posterior / superior portion of vertebral body

62. C. Predominantly Vertebrae 1. Spondylo – Epiphyseal Dysplasia . 2. Pseudo – Achondroplasia . 3. Diastrophic Dysplasia . 4. Rare Syndromes .

63. 2. Pseudo-Achondroplsia Heterogeneous of dominant & recessive . Short – limb dwarfism . Normal craniofacial appearance when compared with achondroplasia . Some spinal deformity . Genu varus & valgus deformity .

64. X-rays : Vertebral bodies are flat , biconvex & have irregular end plates . Become normal towards puberty . Pelvis .. Hypo-plastic & flattened acetabulae . Epiphysis & metaphysis of long bones are abnormal . Tubular bones are short & broad .

65. C. Predominantly Vertebrae 1. Spondylo – Epiphyseal Dysplasia . 2. Pseudo – Achondroplasia . 3. Diastrophic Dysplasia . 4. Rare Syndromes .

66. 3. Diastrophic Dysplasia Autosomal recessive . Appears at birth . Short limb dwarf . Joint contructures & stiff equinus deformity . Proximally set limbs ”hitchhiker”. Cystic swelling of pinnae .

67. Scoliosis is severe . Mentally normal . X-Rays : Kypho-scoliosis . Epiphysis of long bones are flat . Metaphysis are flared . Phalanges , MC , MT are wide & short . Acetabulae wide & femoral heads flat & irregular with varus neck .

68. C. Predominantly Vertebrae 1. Spondylo – Epiphyseal Dysplasia . 2. Pseudo – Achondroplasia . 3. Diastrophic Dysplasia . 4. Rare Syndromes .

69. 4. Rare Syndromes A. Metatropic Dysplasia.. Short limb dwarf at birth and late in infancy short trunk dwarf due to rapidly progressive kyphoscoliosis . B. Spondylometaphyseal Dysplasia.. Common, heterogeneous , disproportionate short stature & x-rays of platyspondyly and metaphyseal irregularity . Kniest Dysplasia.. Rare & resembles metatropic dysplasia .

70. Continue…Classification of Bone Dysplasia 3. Changes in bone density ; increased vs. decreased 4. Craniotubular disorders . 5. Craniofacial abnormalities . 6. Vertebral anomalies . 7. Lysosomal storage disorders . 8. Abnormalities of cartilage & fibrous tissues . 9. Miscellaneous disorders .

71. 3. Changes in the Bone Density Increased : A. Osteopetrosis … Infantile . Intermediate . Tarda ( Adult ) . B. Pycnodysostosis . Decreased : Osteogenesis Imperfecta .

72. Increased bone density… A.Osteopetrosis : Heterogeneous . 3 forms : Infantile … rare , stillbirth is common & surviving infants show anaemia , hepatosplenomegaly , cranial nerves palsy and delayed dentition . Intermediate … occurs sometimes . Tarda … adult form , autosomal dominant .

73. Continue .. Osteopetrosis, tarda form Cranial nerves compression causing facial palsy & deafness . Pathological fractures . Xrays : Thick calvarium with basal sclerosis , vertebral end-plate sclerosis causing a banded appearance “ the rugger-jersey ” spine , cortices of long bones are widened & dense giving rise to an “ endbone ” or “ bone within bone ” appearance.

74. 3. Changes in the Bone Density Increased : A. Osteopetrosis … Infantile . Intermediate . Tarda ( Adult ) . B. Pycnodysostosis . Decreased : Osteogenesis Imperfecta .

75. Increased bone density… B.Pycnodysostosis Rare . Short stature . Generalized increase in bone density . Face is small & triangular . Mandible is under-developed with obtuse angle Hands are short & square with stubby fingers . Dentition is abnormal . Pathological fractures .

76. Xrays : Generalized sclerosis . Little abnormality of modelling . Skull..large calvarium , wide suture lines,persistant fontanelles , wormian bones , hypoplastic facial skeleton . Terminal phalanges are short & irregular . Madelung’s deformity .

77. 3. Changes in the Bone Density Increased : A. Osteopetrosis … Infantile . Intermediate . Tarda ( Adult ) . B. Pycnodysostosis . Decreased : Osteogenesis Imperfecta .

78. Decreased bone density… Osteogenesis Imperfecta Bone fragility . Common bone dysplasia . Heterogeneous . 2 forms : Congenita . Tarda .

79. Osteogenesis Imperfecta… 2 forms.. Congenita : Severe , stillbirth , or early death. Genetics uncertain , but some are autosomal recessive & some are new mutations . Head large , soft calvarium & wide fontanelles . Tarda : Less severer . Can continue to adult life. Majority autosomal dominant but some are heterogeneous & genetics are obscure and can be difficult . Multiple fractures which heal rapidly & bruising tendency .

80. Osteogenesis Imperfecta..continue Congenita…. Disproportionate shortening of limbs . Xrays : skull has poor ossification , wide sutures & many wormian bones . Multiple fractures , spinal deformity with biconcave or flattened vertebrae . Limbs are short & wide or slender & narrow . Tarda ... Sclerae blue , poor dentition & laxity of ligaments . Xrays : skull , multiple fractures , spinal deformity and abnormal limbs are the same as in the congenita .

81. 4.Cranio-tubular Disorders