This document summarizes various developmental disorders, categorizing them based on the type of skeletal changes involved. It describes disorders affecting cartilage and bone growth at the physis and metaphysis, epiphyses, diaphysis, and combined or mixed sites. For each disorder, it provides brief details on characteristics, inheritance, and in some cases treatment. Overall, the document reviews a wide variety of genetic defects that can cause similar clinical syndromes affecting skeletal development and growth.

2. DEVELOPMENTAL
DISORDERS
Variety of gene defects may cause almost
identical clinical syndromes…

3. DEVELOPMENTAL DISORDERS
• CHONDRO-OSTEODYSTROPHIES
(Disorders of Cartilage & Bone growth)
• CONNECTIVE TISSUE DISORDERS
(Heritable defects of Collagen synthesis)
• METABOLIC DEFECTS
(decreased enzyme control ---- genetic disorder)

4. Dysplasias
with
Physeal &
Metaphysea
l changes
Dysplasias
with
Epiphyseal
changes
Dysplasias
with
Diaphysea
l changes
Combined
& mixed
Dysplasias
CHONDRO-
OSTEODYSTROPHIES
(Disorders of
cartilage & bone
growth)

5. PHYSEAL & METAPHYSEAL CHANGES
1) Hereditary Multiple Exostosis (Diaphyseal Aclasis)
2) Achondroplasia
3) Hypochondroplasia
4) Dyschondrosteosis
5) Metaphyseal Chondrodysplasia (Dysostosis)
6) Dyschondroplasia(Enchondromatosis/Ollier’s disease)
7) Mafucci’s syndrome

6. Hereditary Multiple Exostosis
Hard lumps (enlarge later) at ends of long bones and
along apophyseal borders of scapula / pelvis. (lumps
pressure on nerve/vessels).
severely affected bones become short.
Typical:
Wrist ulnar deviation, Radius bowing/subluxation,
Valgus knees/ankles
Unrestricted transverse growth of cartilagenous
physis (growth late)– Exostosis
Treatment:
Removal of exostosis.
Osteotomy for deformities .

9. Achondroplasia (commonest short stature)
• Stunted growth,
• limbs short proximal segment/large skull with
prominent forehead and saddle shaped nose
• Fingers stubby(trident hands)
• Joint laxity
• Thoracolumbar kyphosis in (infants) disappears
later in a year
• Trunk longer than limbs (childhood)
• Back lordosis, buttock prominent
• (adulthood) vetebral pedicles shortening-
ivdp/stenosis

10. Abnormality of endochondral
longitudinal growth, tubular
bone shortening. Membrane
bone formation(skull) is
unaffected.
Treatment: under cord
compression, operative
correction.

13. Hypochondroplasia
• Mild form of
achondroplasia
• Stocky individuals
• Xray : pelvis flattening
thickening of long
bones
Treatment:
Limb lengthening

17. Dyschondrodystosis
Disproportionate shortening of limbs.
Middle segments (forearm/leg) are
affected.
stature reduced but not as in
achondroplasia.
Xray: short forearm/leg
bow radius
madelung’s deformity of
wrist
Treatment:
operative

20. Metaphyseal chondrodysplasia (dysostosis)
Short limb dwarfism
Resembles rickets
Bilateral coxa vara
Bowed legs
Waddling gait
Deformities @ hip/knee
Sub types:
SCHMID
McKUSICK
JANSEN

21. SCHMID TYPE
CLASSICAL FEATURES (autosomal dominant)

24. McKUSICK TYPE (autosomal recessive)
Associated with sparse hair growth

25. JANSEN TYPE (RARE SPORADIC)
PRESENT WITH DEAFNESS

26. Dyschondroplasia /Enchondromatosis/Ollier’s disease
Rare but easily recognised
Defective transformation of
physeal cartilage into bone
unilateral short limb
Valgus/varus deformity
knee/ankle
Shortened ulna
Bowing radius
Crippled hand
(Fingers/toes have multiple
enchondromata characteristic
of disease)

30. Mafucci’s syndrome(rare)
characterised by multiple
enchondromas.
Soft tissue
haemangiomas
(skin/viscera).
Malignant changes in
soft tissue and bone
lesions.

34. EPIPHYSEAL CHANGES
1) Multiple Epiphyseal Dysplasia (MED)
2) Spondyloepiphyseal Dysplasia (SED)
3) Dysplasia Epiphysealis Hemimelica (Trevor’s disease)
4) Chondrodysplasia Punctata (slipped epiphysis) or
(Conradi’s disease)

35. Multiple Epiphyseal Dysplasia
• Mild anatomical abnormalities to severe crippling
condition
• Vertebrae are not at all affected (slightly)
• Lower limbs short compared to trunk
• Waddling gait
• Hip/knee pain
• In hips mistaken to perthes disease
• @ maturity femoral/humerus head/condyles flattened
• Treatment: osteotomy/corrective /reconstructive
surgery.

38. SPONDYLO EPIPHYSEAL DYSPLASIA
• Vertebral changes(platyspondyly)
• Delayed ossification (irregular ring epiphyses)
• Indentation of endplates(schmorl nodes)
• Sub types:
SED Congenita (autosomal dominant)
infancy, neck hardly present, barrel chest,
short limbs, odontoid hypoplasia
scoliosis/lordosis
SED Tarda (x-linked recessive)
diagnosed only after 5 years
barrel chest
backache

41. CONGENITA TARDA

43. DYSPLASIA EPIPHYSEALIS HEMIMELICA
(TREVOR’S DISEASE)
• Hemi dysplasia (only one limb) or (one half
medial/lateral)
• Mostly knee/ankle (mostly in boys)
• Bone swelling on one side of the joint.
• Treatment:
Excess bone removed.

46. CHONDRO DYSPLASIA PUNCTATA
(SLIPPED EPIPHYSES) or (CONRADI’S DISEASE)
• Multisystem disorder
• Facial abnormalities, vertebral anamolies,
• Asymmetrical epiphyseal changes, bone changes
• Severe cases (cardiac abnormalities, cataracts, mental
retardation)
• X-ray: punctate stippling of cartilagenous epiphyses & apophyses
upto 4 years, later disappear and follow epiphyseal irregularities and
dysplasia.

50. Stippled epiphyses

51. DIAPHYSEAL CHANGES
1) Metaphyseal Dysplasia (Pyle’s disease)
2) Craniometaphyseal Dysplasia
3) Osteopetrosis (Marble’s bones)(Albers Schonberg disease)
4) Diaphyseal Dysplasia (Engelmann’s) or (Camurati’s disease)
5) Craniodiaphyseal Dysplasia
6) Pyknodysostosis
7) a) Melorheostasis (Leri’s disease) (Candle bones)
b) Osteopoiklosis (Spotted bones)
c) Osteopathia striata (Stripped bones)

52. METAPHYSEAL
DYSPLASIA (PYLE’S
DISEASE)
Autosomal Recessive.
significant feature is
genu valgum.
X-ray : bottle shaped
distal femur/proximal
tibia
(Erlenmeyer Flask
Deformity)

53. Erlenmeyer flask “Bottle shape”
distal femur/proximal tibia

54. Craniometaphyseal Dysplasia
• Autosomal dominant
• Proximal forehead(thickening of skull &
mandible.)
• Large jaw
• Squashed nose
• Foraminal occlusion may occur.

55. Craniometaphyseal dysplasia

57. OSTEOPETROSIS
(MARBLE BONES/ ALBERS SCHONBERG DISEASE)
• Thickening & increased density of bones
• Two types
• a) osteopetrosis tarda
seldom symptoms,
discovered in adulthood(after fracture/x-ray),
vertebral end plates sclerosed & shows
stripped appearance (Rugger- Jersey Spine)
• b) osteopetrosis congenita
rare (autosomal recessive)
pancytopenia, haemolysis, anaemia,
hepatosplenomegaly,
optic nerve palsy/facial nerve palsy,
Repeated haemorrhage leads to death

58. OSTEOPETROSIS TARDA

59. OSTEOPETROSIS AUTOSOMAL DOMINANT

62. OSTEOPETROSIS CONGENITA (AUTOSOMAL
RECESSIVE)

63. OSTEOPETROSIS CONGENITA

64. DIAPHYSEAL DYSPLASIA
(ENGELMANN’S or CAMURATI’S DISEASE)
• Rare
• X-ray :
• Fusiform widening of
bones
• sclerosis of shaft of long
bones
• muscle pain/weakness
• waddling gait

65. Camurati’s disease

66. CRANIODIAPHYSEAL DYSPLASIA
• Rare , autosomal
recessive
• Cylindrical
expression of bone
• Prominent facial
contours in
childhood-
striking features -
LEONTIASIS
• Foraminal
occlusion may
cause deafness/
visual impairment.

70. PYKNODYSOSTOSIS
• Short stature
• Frontal bossing
• Mandible underdevelopment
• Abnormal dentition
• X-Ray: skull enlarged with wide sutures/ open
fontanellae
• Facial/mandible hypoplastic --- triangled facies

74. CANDLE BONES (MELORHEOSTASIS / LERI’S DISEASE)
• Rare, Non
Familial
• Discovered
accidently with
pain & stiffness
of limb
• X-ray : Patch of
sclerosis appears
as a burning
candle with wax
that congeals

78. OSTEOPOIKLOSIS (SPOTTED BONES)
X-Rays: white spots through skeleton

80. STRIPPED BONES (OSTEOPATHIA STRIATA)
• X-RAYS :
• Inceased density
parallel to shaft.
• Radiates like a fan
in pelvis

83. COMBINED & MIXED DYSPLASIAS
shows mixture of epiphyseal, metaphyseal & vertebral defects
1) Spondylometaphyseal Dysplasia
2) Pseudo Achondroplasia
3) Diastrophic Dysplasia (recessive)
4) Cleidocranial Dysplasia (dominant)
5) Nail-Patella syndrome (dominant)
6) Craniofacial Dysplasia

84. SPONDYLOMETAPHYSEAL DYSPLASIA
• Commonest
• platyspondyly
• kyphoscoliosis

86. PSEUDO ACHONDROPLASIA
• Rare
• Short limb Dwarf with ligament laxity
• c/f appear after 1 or 2 years
• Increased lordosis
• Bow leg
• Ovalshape vertebrae

88. DIASTROPHIC DYSPLASIA
Cartilage affected
Dwarf, distorted,
hand deformity (hitch hiker’s thumb)
Club feet
Joint contractures, dislocations,
Cauliflower ears
Cleft palate
Spinal fusion
Respiratory distress (due larynx cartilage)

91. CLEIDO-CRANIAL DYSPLASIA
Hypoplasia
of clavicle
Flat bones
Short, large
head,
Frontal
prominence,
Flat face,
drooping
shoulder

93. NAIL-PATELLA SYNDROME
• (dominant)
• Nail hypoplasia,
• Patella absent/small
• Radius head subluxed
• Elbows lack extension
• Congenital nephropathy
• Iliac blades have bony protrubrence (horns)

97. CRANIOFACIAL DYSPLASIA
• Odd face appearance
• Cranial suture fusion
• Exophthalamus
• Mental retardation
• Hand/feet abnormalities
• Apert’s syndrome (egg shape head)
• Acrocephalosyndactyly
• Syndactyly of rays

99. CONNECTIVE TISSUE DISORDERS
(Hereitable defects of Collagen synthesis)
1) Generalized Joint Laxity (familial)
2) Marfan’s syndrome
3) Ehler’s Danlos syndrome
4) Larsen’s syndrome
5) Osteogenesis imperfecta (brittle bones)
6) Fibrodysplasia Ossificans progressiva
(Myositis Ossificans progressiva)
7) Neurofibromatosis

100. Generalized Joint Laxity
• Joint hyper mobility
passive hyper-extensive of mcp joints beyond 90
degree.
passive stretching of thumb to touch front forearm
Hyperextension of elbows & knees
Ability to bend forward & touch flat on floor with
hands

103. MARFAN’S SYNDROME
Due to cross linkage defect in collagen and elastin
(genetic mapping is fibrillin gene on chromosome 15)
c/f :
Tall with long legs and arms
Chest pectus excavatum(flat/hollowing)
Digits long(spider fingers- arachnodactyly)
Spine spondylolisthesis, scoliosis
Flatfeet
Associated: high arched palate, hernia, lens dislocation, retinal
detachment, aortic aneurysm, mitral/aortic incompetence, joint laxity

111. EHLERS DANLOS SYNDROME (dominant)
Abnormality in collagen & elastin
c/f: unusual skin laxity, joint hyper mobility, vascular
fragility,hypotonia

114. LARSEN’S SYNDROME
• Recessive
• Severe forms in infancy
joint laxity, hip dislocation, knee instability,
radial head subluxation, equinovarus feet, ‘dish’ face
• Spine deformities in older children

118. OSTEOGENESIS IMPERFECTA
(BRITTLE BONES)
Commonest genetic disorder of bone
Type 1 collagen (abnormal synthesis & structure)
Abnormalities of bones, teeth, sclerae and skin
c/f:
Osteopenia
Liability to fracture
Laxity of ligaments
Blue sclerae
Dentinogenesis imperfecta (crumbling teeth)

124. FIBRODYSPLASIA OSSIFICANS PROGRESSIVA
(MYOSITIS OSSIFICANS PROGRESSIVA)
Characterised by ossificans of muscle connective
tissue (trunk mostly)
Starts with fever & inflammation in early childhood
Associated : shortening of big toe & thumb

129. NEUROFIBROMATOSIS
• Commonest gene disorder affecting skeleton
• Type 1 (NF 1) = VON Reckling hausen’s disease
• (abnormality is in the gene which codes for neurofibromin on
chromosome 17)
characteristic lesions are --- schwann cell tumors(neuro fibromata)
patches of skin pigmentation (café-au-lait
spots)

133. Type 2 rare (gene defect which codes for
schwannomin on chromosome 22)
Scoliosis & soft tissues overgrowth
(elephantiasis)
Vertebral anamolies (scalloping of posterior
aspects of vertebral bodies, erosion of
pedicle,pencilling of ribs, i.v. foramin
enlargement)

137. METABOLIC DEFECTS
(decreased enzyme control ---- genetic disorder)
1) Mucopolysaccharidases
2) Gaucher’s disease
3) Homocystinuria
4) Alkaptonuria
5) Congenital hyperuricaemia (Lesch-Nyhan syndrome)

138. Mucopolysaccharidases MPS
• Due lack in enzyme, there will be stoppage in
degradation pathway of proteoglycans (GAG)
• C/F :
all are autosomal recessive except Hunter’s syndrome (x linked)
Short stature with vertebral deformity
Facies coarseness
Hepatosplenomegaly
Mental retardation
Out of 10 different disorders, 3 rare conditions are:
Hurler’s Hunter’s Morquiobrailsford syndrome

139. HURLER’S SYNDROME MPS-1

140. HURLER’S SYNDROME
• 2-3 Years (death in childhood)
• Kyphosis
• Protruding tongue
• Hearing loss
• Mental retarded
• Poor speech
• spatulate ribs/clavicles
• Coxa valga
• Cardiorespiratory problems

141. HUNTER’S SYNDROME MPS-2

142. HUNTER’S SYNDROME
• Less severe
• X linked
• Males affected
• Appear at 3 year
• Teenage death
• (similar to hurler’s)

144. MORQUIOBRAILSFORDS SYNDROME
• Walking delayed
• Protuberant sternum
• Hearing loss
• Face unaffected
• Genu valgum
• Odontoid hypoplasia
• Treatment : enzyme replacement, gene correction

145. MORQUIO BRAILSFORD SYNDROME

147. Gaucher’s disease
• Each tissue a cell dies, cell membrane releases
glucocerbroside which binds with dglucose
molecule.
• This bond is split by an enzyme glucosylceramide
betaglucosidase. Lack of enzyme causes
accumulation/enlargement of marrow,spleen,liver
• Rare form- cns affected causes death with in year
• Subacute form- hepatosplenomegaly
(neuro/skeletal abnormalities in childhood)
• Chronic form- pancytopenia

148. • c/f:
Bone pain, osteonecrosis(femur), distal
femur(erlenmeyer flask shape)
Treatment: symptomatic, enzyme replacement

153. c/f:
Bone pain,
osteonecrosis(femur), distal
femur(erlenmeyer flask
shape)
Treatment: symptomatic,
enzyme replacement

157. Homocystinuria
• Deficiency of enzyme cystathionine beta synthetase
and accumulation of homocysteine and methionine.
• c/f:
patients tall and thin (as in marfan’s disease)
Osteoporosis, mental retardation, thromboembolic
disease common
Treatment: can be cured by pyridoxine (B6)

161. Alkaptonuria
• Deficiency of enzyme homogentistic acid oxidase
and accumulation of homogentistic acid & executed
in urine.
• C/f:
• Alkaptonuria= urine turns dark
• Ochronosis=cartilage + other connective tissues are
grey stained
• Calcification of IVD.

167. Congenital hyperuricaemia
(Lesch-Nyhan syndrome)
• Rare x-linked recessive
• Absence of enzyme hypoxanthine guanine phospho
ribosyl transferase (HGPRT)
• Results in excessive uric acid and gout
• c/f:
• Young boys mental retardation and prone to self
Mutilation (gnawing the ends of teeth)
Mild cases with severe gout.

172. Thank
you