An Overview of Skeletal Dysplasia. Abnormality of skeleto muscular system resulting into deformities, growth arrest and functionalLimitations

1. Dr. Ashok Bhatt
Consultant Orthopaedic Surgeon

2. Skeletal dysplasias are a heterogeneous group of more than 200
disorders characterized by abnormalities of cartilage and bone
growth, resulting in abnormal shape and size of the skeleton
and disproportion of the long bones, spine, and head.
patients with disproportionately short stature have skeletal
dysplasia (osteochondrodysplasia).
Short stature is defined as height that is 3 or more standard
deviations below the mean height for age. If short stature is
proportional, the condition may be due to endocrine or
metabolic disorders or chromosomal or nonskeletal dysplasia
genetic defects.

3. During the 1950s and 1970s, many new bone dysplasias were
identified based on clinical manifestations, radiographic
findings, inheritance patterns, and morphology of the growth
plate.
In the 1980s, research focused on defining the natural history
and variability of the disorders.
In the 1990s, the focus shifted toward mutations and the
pathogenetic mechanisms
In 1997, the International Working Group on Bone Dysplasias
proposed a newly revised "International Nomenclature and
Classification of the Osteochondrodysplasias

4. Families of disorders -based on recent etiopathogenetic information concerning
the gene and/or protein defect involved
Component disorders result from mutations of the identical gene
Based on molecular genetic cause, the dysplasias grouped by the function of the
protein product of the causative gene
Many of the genes mutated in skeletal dysplasias encode proteins that play
critical roles in the growth plate.
An understanding of the role in growth plate function gives important clues into
the molecular pathology of the skeletal dysplasia
Mutations in type II collagen cause a large number of disorders classified as
spondyloepiphyseal dysplasia
Mutations in type IX collagen and cartilage oligomeric protein, cause multiple
epiphyseal dysplasia

6.  Epiphysial Dysplasia
A) Epiphysial Hypoplasia
1. Failure of cartilage – SED congenita & tarda
2. Failure of ossification – MED congenita & tarda
B) Epiphysial hyperplasia
1. Dysplasia epiphysialis hemimelica
 Physial Dysplasias
A) Cartilage hypoplasia
1. Failure of proliferation – Achondroplasia cong. & tarda
2. Failure of hypertrophic – Metaphysial dysostosis
B) Cartilage hyperplasias
1. Excess proliferation – Hyperchondroplasia
2. Excess hypertrophy - Enchondromatosis

7.  Metaphyseal Dysplasias
A) Metaphysial hypoplasias
1. Failure of primary spongiosa – Hypophosphatasia
2. Failure to absorb primary Spongiosa - Osteopetrosis
3. Failure to absorb sec. spongiosa – Craneo met.dysplas
B) Metaphysial hyperplasia
1. Excessive spongiosa – Multiple exostosis
 Diaphyseal Dysplasias
A) Diaphyseal hypoplasia
1. Failure of perio. Bone formation – Osteogen. Imperfecta
2, Failure of endo. Bone formation- Idio.osteoporosis
B) Diaphyseal hyperplasia
1. Exc. Perio.bone – progressive diaphyseal dysplasia
2. Exc. Endo. Bone - Hyperphosphatasemia

8. The overall incidence -1 case per 4000-5000 births.
The true incidence may be twice as high.
Lethal skeletal dysplasias - 0.95 per 10,000 deliveries.
4 most common skeletal dysplasias are thanatophoric dysplasia, achondroplasia,
osteogenesis imperfecta, and achondrogenesis
Thanatophoric dysplasia and achondrogenesis account for 62% of all lethal
skeletal dysplasias.
Achondroplasia is the most common nonlethal skeletal dysplasia.
infants with skeletal dysplasias detected at birth, approximately 13% are stillborn,
and 44% die during the perinatal period.
The overall frequency of skeletal dysplasias in infants who die perinatally is 9.1
per 1000

9. Males are primarily affected in X-linked recessive disorders.
X-linked dominant disorders may be lethal in males.
Skeletal dysplasias are usually detected in the newborn period or
during infancy.
Some disorders may not manifest until later in childhood

10. Family History
Spontaneous abortions / still births
Parents , siblings & other relatives
Multiple affected siblings – normal parents – Auto.Rece
Affected parent – Autosomal dominant pattern
Abortion/still birth male / female = X linked
Affected male & maternal uncle = X recessive nature
Pregnancy & Birth history
Maternal hydramnios
Fetal hydrops
Reduced Fetal activity - lethal types of skeletal dysplasia
warfarin or phenytoin - stippling of the epiphyses
Still births - lethal chondrodysplasias

11. Anthropometric parameters ~ gestational age / chronologic age
short-limb skeletal dysplasia
 Rhizomelic shortening - short proximal segment (achondroplasia,
hypochondroplasia, chondrodysplasia punctata, congenital short femur.
spondyloepiphyseal dysplasia, Jansen type of metaphyseal dysplasia
 Mesomelic shortening - short middle segments (Langer and Nievergelt types of
mesomelic dysplasias, Robinow syndrome, and Reinhardt syndrome
 Acromelic shortening – short distal segments (acrodysostosis and peripheral
dysostosis )
 Acromesomelic shortening (acromesomelic dysplasia )
 Micromelia – Entire short limb (achondrogenesis, fibrochondrogenesis, Kniest
dysplasia, dys-segmental dysplasia, and Roberts syndrome.)
 Short trunk (Morquio syndrome, Kniest syndrome, Dyggve-Melchior-Clausen
disease, metatrophic dysplasia, SED, and spondyloepimetaphyseal dysplasia
(SEMD).

12. Skeletal dysplasias associated with mental retardation
 CNS developmental anomalies (hydrocephaly, porencephaly,
hydranencephaly, agenesis of corpus callosum , and Rubinstein-Taybi syndrome
 Intracranial pathologic processes (Craniostenosis syndromes (pressure) and
thrombocytopenia-radial aplasia syndrome (bleeding)
 Neurologic impairment (Dysosteosclerosis (progressive cranial nerve
involvement) and mandibulofacial dysostosis (deafness)
 Chromosome aberrations - Autosomal trisomies
 Primary metabolic abnormalities - Lysosomal storage diseases
 Chondrodysplasia punctata
 Warfarin embryopathy (teratogen)
 Cerebrocostomandibular syndrome (hypoxia)
Skull :
 Disproportionately large head (Achondroplasia, achondrogenesis )
 Cloverleaf skull - (Apert syndrome, Carpenter syndrome, Crouzon syndrome,
and Pfeiffer syndrome
 Craniosynostosis - (Apert syndrome, Crouzon syndrome, hypophosphatasia

13.  Eyes
Congenital cataract - Chondrodysplasia punctata
Myopia - Kniest dysplasia and SED congenita
 Mouth
Bifid uvula and high arched or cleft palate - Kniest dysplasia), SED
congenita, diastrophic dysplasia, metatrophic dysplasia, and
camptomelic dysplasia
 Ears Acute swelling of the pinnae - Diastrophic dysplasia
 Radial ray defects
Trisomy 18; trisomy 13 - (VACTERL) syndrome; Fanconi anemia;
Cornelia de Lange syndrome; Holt-Oram syndrome; Townes-Brock
syndrome; Okihiro syndrome, Aase syndrome; acrofacial dysostosis;
Levy-Hollister syndrome; TAR syndrome, Roberts syndrome; and
Baller-Gerold syndrome.
 Polydactyly - Preaxial , Postaxial

14.  Hands & Feet
Hitchhiker thumb - Diastrophic dysplasia
Clubfoot - Diastrophic dysplasia, Kniest dysplasia, and osteogenesis
imperfecta
 Nails
Hypoplastic nails - Chondroectodermal dysplasia
Short and broad nails - McKusick metaphyseal dysplasia
 Joints
Multiple joint dislocations, Larsen syndrome and otopalatodigital syndrome
 Long bone fractures : osteogenesis imperfecta syndromes, hypophosphatasia,
osteopetrosis, and achondrogenesis type I)
 Long or narrow thorax : Asphyxiating thoracic dysplasia, chondroectodermal
dysplasia, and metatrophic dysplasia
 Pear-shaped chest : Thanatophoric dysplasia, short-rib polydactyly syndromes, and
homozygous achondroplasia
 Heart : Atrial septal defect or single atrium - Chondroectodermal dysplasia
Patent ductus arteriosus - Lethal short-limbed skeletal dysplasias
Transposition of the great vessels - Majewski syndrome

15. Achondrogenesis DiGeorge Syndrome
Achondroplasia Down Syndrome
Apert Syndrome Failure to Thrive
Child Abuse & Neglect: Failure to
Thrive
Fanconi Syndrome
Constitutional Growth Delay Growth Failure
Cornelia De Lange Syndrome Hyperparathyroidism
Crouzon Syndrome Hypophosphatasia
Cystic Fibrosis McCune-Albright Syndrome
Cystinosis Sialidosis (Mucolipidosis I)
Cytomegalovirus Infection Trisomy 18

16.  Cardiopulmonary disorders
congenital heart defects, severe recurrent pneumonias
 Chromosomal disorders
 Endocrine disorders
pituitary skeletal dysplasia, growth hormone deficiency
 Inborn errors of metabolism - lysosomal storage disorders
 IUGR
 Nutritional disorders - kwashiorkor or marasmus
 Primary growth disturbances
primordial skeletal dysplasia, Seckel syndrome, and Weill-
Marchesani syndrome

17.  Immune function studies
T-cell dysfunction– cartilage-hair hypoplasia (metaphyseal
dysplasia, McKusick type)
 Neutropenia
Shwachman syndrome (metaphyseal dysplasia and pancreatic insufficiency)
 Biochemical studies
serum alkaline phosphatase & urinary phosphorylethanolamine - severe congenital
hypophosphatasia
 urinary glycosaminoglycan -
Kniest dysplasia (keratan sulfate), pseudoachondroplasia, and thanatophoric dysplasia
urinary mucopolysaccharides – MPS
 lysosomal enzymes - lysosomal storage disease

18. Conventional radiography – Most useful diagnostic tool
The skeletal survey - skull (anteroposterior [AP], lateral, and Towne
views), chest (AP), spine (AP and lateral), pelvis (AP), tubular bones
(AP), and/or hands and feet (AP)
 Oval translucent area in proximal femora and humeri - Achondroplasia
 Bowing of limbs (camptomelia) : Camptomelic dysplasia, osteogenesis imperfecta syndromes,
and thanatophoric dysplasia
 Spikes at lateral femoral metaphyses : Thanatophoric dysplasia and achondrogenesis type I & II
 Cupping of the ends of the rib and long bones and metaphyseal flaring : Achondroplasia,
metaphyseal dysplasias, asphyxiating thoracic dysplasia, and
chondroectodermal dysplasia
 Long bone fractures : Osteogenesis imperfecta syndromes, hypophosphatasia, osteopetrosis, and
achondrogenesis type I (Parenti-Fraccaro syndrome)
 Absence of epiphyseal ossification centers : SED congenita, multiple epiphyseal dysplasia, and
other SED
 Cone-shaped epiphyses : cleidocranial dysplasia
 Abnormal pelvic configuration : Achondroplasia, Ellis-van Creveld syndrome
 Severe hypoplasia of the scapula: Camptomelic dysplasia and Antley-Bixler syndrome

19.  CT scan and MRI of the skull and brain
Reveal concurrent brain anomalies
3D images - craniofacial anomalies
 MRI of the spine
assess atlantoaxial instability , Spinal canal stenosis,
Narrowing of Foramen magnum, Cord oedema, Gliosis
Compressive Myelopathies, progressive spinal
deformities and scoliosis
 CT 3D reconstruction : surgical planning for osteotomies for
complex pelvic and hip dysplasias
 Other Tests :
Sleep studies, Molecular analyses, Cytogenetic study

20.  Useful in cases with positive history of Dysplasia
 2D ultrasonography : 60 % Reliability
 3D ultrasonography – better tool with more accuracy specially in
facial dysmorphism and anomalies involving the hands and feet
 Appropriate time : 30 weeks’ gestation
 Possible Evaluation : Short limb Dysplasia
thoracic dimensions
fetal ribs
fetal spine
hands and feet
fetal craniofacial structures
fetal movement
maternal hydramnios, fetal hydrops, increased
nuchal translucency thickness, and other fetal anomalies, such as congenital
heart defects and cystic renal malformation .

25.  Close monitoring during antenatal period
 Prenatal detection - influence the obstetric and perinatal treatment
 Treatment is supportive
 Medical care : to prevent neurologic & orthopedic complications
 Neonatal resuscitation and ventilatory support
 Obstructive sleep apnea – Treated by adenotonsillectomy, weight
reduction, continuous airway pressure by a nasal mask, and
tracheostomy in extreme cases
 Monitoring height, weight, and head circumference
 Recombinant human growth hormone treatment

26.  Thoracolumbar kyphosis – Prevented by brace & casts
 Progressive kyphosis – Managed by anterior & posterior fusion
 Canal decompression – To reduce oedema and cord compression
 Correction of scoliosis with newer techniques & fusion
 Ilizarov procedure – To lengthen short bones, correct angular
deformity
 Bone marrow transplantation - congenital immune deficiencies,
mucopolysaccharidosis, lipidosis, osteopetrosis, and Gaucher
disease
 Cesarean delivery - In mothers with skeletal dysplasia
 Plastic reconstructive procedures for cranio facial naso cranial &
complex head & neck deformities.

27.  Intrauterine complications:
Polyhydramnios and fetal hydrops IUGR , Int.Uterine death
 Respiratory complications:
Respiratory distress, upper airway obstruction, hypoxic
episodes
 CNS complications: Hydrocephalus , Foramen Magnum stenosis
 Skeletal complications: C1-C2 InstabilityVertebral abnormalities,
hip dysplasia, tight and loose joints, bowed legs
 Muscular complications: Truncal hypotonia leading to
kyphoscoliosis – Achondroplasia, MPS
 Ophthalmologic complications : Myopia with MED –Stickler’s Syn
Kniest dysplasia and SED congenita
 Dental complications - with many types of chondrodystrophy

28.  Nutritional complications – Obesity, Failure to thrive &
severe malnutrition in oro-pharyngeal-palateal anomalies
 Anesthesia – in some form of chondrodysplasias
 Malignant hyperthermia – in osteogenesis imperfecta
 Numerous obstetric and gynecologic problems

29.  Certain skeletal dysplasia – lethal
 Non lethal dysplasia – normal or near normal life
 prognosis depends on the degree of skeletal abnormalities
and concomitant anomalies.
 Socio-economic and marital concerns
 Psychiatric issues and stigma – less in males Vs Females
 Relevance of the disability label