Skeletal Dysplasia

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Introduction

Skeletal dysplasias also termed as osteochondrodysplasias are a large heterogeneous group of disorders comprising of abnormalities of bone or cartilage growth or texture. Skeletal dysplasia is a group of rare genetic disorders that affect bone growth and development. These disorders are characterized by abnormalities in the size, shape, and structure of bones, resulting in short stature, limb deformities, and other skeletal abnormalities.

They occur due to genetic mutations and their phenotype continues to evolve throughout life. Skeletal dysplasias thus differ from dysostoses which are malformations of single or multiple bones in combination, are due to abnormal blastogenesis in-utero and phenotypically remain static throughout life.

Epidemiology

About 1 in 5,000 babies are born with some type of skeletal dysplasia. Nonetheless, if taken collectively, genetic skeletal dysplasias or osteochondrodysplasias comprise a recognizable group of genetically determined disorders with generalized skeletal affection.

Etiology

Skeletal dysplasia is caused by mutations in genes that are responsible for bone growth and development. These mutations can be inherited from one or both parents, or they can occur spontaneously during fetal development.

Clinical Signs and Symptoms

The symptoms of skeletal dysplasia can vary widely depending on the specific type of disorder and the severity of the condition. However, some common symptoms include:

Short stature: Individuals with skeletal dysplasia are typically shorter than average for their age and gender.

Limb deformities: Skeletal dysplasia can cause abnormalities in the size and shape of the limbs, including bowed legs, knock-knees, and curved spine.

Joint pain: Skeletal dysplasia can cause joint pain and stiffness, particularly in the hips and knees.

Breathing difficulties: In some cases, skeletal dysplasia can cause narrowing of the airways, leading to breathing difficulties.

Dental abnormalities: Some types of skeletal dysplasia can cause abnormalities in the teeth, including missing or misshapen teeth.

Skeletal dysplasia Classification

The first 8 groups of conditions in the 2010 nosology are separated according to the molecular basis of the disease: FGFR3, type 2 collagen, type 11 collagen, sulfation disorders, perlecan, aggrecan, filamin, and TRPV4. The other 32 groups are organized according to their clinical and radiographic presentation. The prefix acro- refers to the extremities (hands and feet), meso- to the middle portion (ulna and radius, tibia and fibula), rhizo- to the proximal portion (femur and humerus), spondylo- to the spine, epi- to the epiphyses, and meta- to the metaphyses. For example, if only the hands and feet are shorter, one would consult the acromelic group of conditions, whereas if the spine and metaphyses are affected, one would consult the spondylometaphyseal dysplasias. Listed below are the 40 groups of conditions to be detailed in this chapter.

Groups of conditions organized according to their molecular bases

1. FGFR3 chondrodysplasia group
2. Type 2 collagen group and similar disorders
3. Type 11 collagen group
4. Sulfation disorders group
5. Perlecan group
6. Aggrecan group
7. Filamin group and related disorders
8. TRPV4 group

Group of conditions according to their clinical presentations;

9. Short-ribs dysplasias (with or without polydactyly) group

10.Multiple epiphyseal dysplasia and pseudoachondroplasia group

11.Metaphyseal dysplasias

12.Spondylometaphyseal dysplasias (SMD)

13.Spondylo-epi-(meta)-physeal dysplasias (SE(M)D)

14.Severe spondylodysplastic dysplasias

15.Acromelic dysplasias (extremities of the limbs)

16.Acromesomelic dysplasias (extremities and middle portion of the limbs)

17.Mesomelic and rhizo-mesomelic dysplasias (proximal and middle portions of the limbs)

18.Bent bones dysplasias

19.Slender bone dysplasia group

20.Dysplasias with multiple joint dislocations

21.Chondrodysplasia punctata (CDP) group

22.Neonatal osteosclerotic dysplasias

23.Increased bone density group (without modification of bone shape)

24.Increased bone density group with metaphyseal and/or diaphyseal involvement

25.Osteogenesis imperfecta and decreased bone density group

26.Abnormal mineralization group

27.Lysosomal storage diseases with skeletal involvement (dysostosis multiplex group)

28.Osteolysis group

29.Disorganized development of skeletal components group

30.Overgrowth syndromes with skeletal involvement

31.Genetic inflammatory/rheumatoid-like osteoarthropathies

32.Cleidocranial dysplasia and isolated cranial ossification defects group

33.Craniosynostosis syndromes

34.Dysostoses with predominant craniofacial involvement

35.Dysostoses with predominant vertebral with and without costal involvement

36.Patellar dysostoses

37.Brachydactylies (with or without extraskeletal manifestations)

38.Limb hypoplasia—reduction defects group

39.Polydactyly-Syndactyly-Triphalangism group

40.Defects in joint formation and synostoses