Frank Horan

ORTHOPAEDIC ASPECTS OF THE EHLERS. DANLOS SYNDROME

1. The orthopaedic features of 100 patients with the Ehlers-Danlos syndrome are described. 2. The significance of these findings is discussed and comment is made of their relationship to the other stigmata of the syndrome.

A review of the osteopetroses.

The osteopetroses are a group of conditions which are characterized by varying combinations of bony sclerosis and modelling defects. Classical osteopetrosis may be inherited as an autosomal dominant or autosomal recessive: the former variety is benign, heterogeneous and comparatively common, while the latter is precocious, potentially lethal and rare. Many other craniotubular dysplasias and hyperostoses are loosely grouped with the osteopetroses. The commonest of these is the autosomal dominant form of craniometaphyseal dysplasia, while the others which are well known include Pyle disease, and van Buchem disease. Sclerosteosis is a progressive condition in which massive cranial thickening is associated with syndactyly and gigantism. Each of these disorders has specific clinical and radiographic features, which permit recognition. Diagnostic accuracy is crucial for treatment, prognostication and effective genetic management.

Osteopathia striata with cranial sclerosis. An autosomal dominant entity.

The syndromic association of striae in the long bones and pelvis, together with sclerosis of the base of the skull, has been investigated in four families. Impairment of hearing and alteration in the shape of the head are the most important clinical manifestations. Spinal abnormalities are an inconsistent feature. The distribution of affected individuals in the kindreds is compatible with autosomal dominant inheritance.

Craniometaphyseal dysplasia--variability of expression within a large family.

Fifteen individuals in five generations of a kindred with branches in South Africa and England had the autosomal dominant form of craniometaphyseal dysplasia. The majority of affected adults had mild to moderate mandibular distortion, while paranasal bossing was a transient manifestation in childhood. Facial palsy with onset in childhood was present either unilaterally or bilaterally in about 30% of the patients, while 50% had auditory dysfunction which varied from mild impairment of hearing to total deafness. Stature and intellect were normal, and bone fragility, osteomyelitis and dyshaemopoesis were not features of the condition. Five other potentially affected family members had deafness or facial palsy of uncertain aetiology in the absence of other stigmata of CMD. It is uncertain whether these complications represent minor degrees of phenotypic expression of the abnormal gene.

DOMINANT INHERITANCE IN FAMILIAL GENERALISED ARTICULAR HYPERMOBILITY

Two individuals with generalised articular hypermobility are described. There are many affected members in both kindreds, and the pedigrees indicate that the disorder is transmitted as an autosomal dominant trait. Orthopaedic complications and deformities are common in one family but absent in the other. It is suggested therefore that the two disorders are distinct and separate genetic entities.

Spondylocostal dysostosis in South African sisters

The clinical and radiographic features of two sisters with a severe form of spondylocostal dysostosis (SCD) are described and depicted. Autosomal recessive inheritance is likely.

Autosomal recessive inheritance of osteogenesis imperfecta

Six individuals in two closely related families in Southern Africa had osteogenesis imperfecta (OI). Although OI is usually inherited as an autosomal dominant, the pattern of transmission in this kindred was consistent with autosomal recessive inheritance.

Orthopaedic aspects of the Schwartz syndrome

The Schwartz syndrome is a rare disease characterized by skeletal dysplasia, short stature, and myotonia. The affected individuals have a mask-like facies, with blepharophimosis and ptosis. The condition, which most likely is inherited as an autosomal recessive, is being recognized with increasing frequency, and we have been able to find descriptions of fourteen patients with this syndrome in the world literature. In this paper we give details of the skeletal findings in two affected brothers and discuss them on the basis of a review of all previously reported cases.

Orthopaedic problems in inherited skeletal disorders

1. Genetic Principles.- 1.1 Basic Genetics.- 1.2 Chromosomal Disorders.- 1.3 Gene Disorders.- 1.3.1 Autosomal Dominant.- 1.3.2 Autosomal Recessive.- 1.3.3 X-Linked Inheritance.- 1.3.4 Polygenic Inheritance.- 2. The Investigation and General Management of Bone Dysplasias.- 2.1 Assessment of the Patient.- 2.1.1 Clinical Examination.- 2.1.2 Genealogical Studies.- 2.1.3 Radiological Assessment.- 2.1.4 Biochemical Investigation.- 2.2 Other Investigations.- 2.2.1 Radio-isotope Scanning of Bone.- 2.2.2 Computerised Tomography.- 2.2.3 Histological Studies.- 2.2.4 Histochemical Studies.- 2.3 Antenatal Diagnosis.- 2.3.1 Amniocentesis.- 2.3.2 Foetoscopy.- 2.3.3 Antenatal Radiography.- 2.3.4 Ultrasonography.- 2.3.5 General Considerations.- 2.4 The General Management of Bone Dysplasias.- 2.4.1 Psycho-social Problems.- 2.4.2 General Considerations.- 2.4.3 Dwarfism.- 2.4.4 The Lower Limbs.- 2.4.5 Genetic Counselling.- 3. Nomenclature and Terminology.- 3.1 Introduction.- 3.2 Historical Perspectives.- 3.3 Nomenclature.- 3.4 Classification.- 3.5 Terminology.- 3.6 Current Trends.- 4. Disorders of Epiphyses and Metaphyses with Predominant Epiphyseal Involvement.- 4.1 Multiple Epiphyseal Dysplasia.- 4.2 Chondrodysplasia Punctata.- 4.2.1 Conradi-Hunerman Type.- 4.2.2 Rhizomelic Form.- 4.3 Dysplasia Epiphysealis Hemimelica.- 5. Disorders of Epiphyses and Metaphyses with Predominant Metaphyseal Involvement.- 5.1 Achondroplasia.- 5.2 Hypochondroplasia.- 5.3 Metaphyseal Chondrodysplasia.- 5.3.1 Schmid Type.- 5.3.2 Jansen Type.- 5.3.3 McKusick Type.- 5.3.4 Other Forms.- 5.4 Vitamin D-Resistant Rickets.- 6. Disorders of the Epiphyses and Metaphyses with Major Vertebral Involvement.- 6.1 Spondyloepiphyseal Dysplasia.- 6.1.1 Spondyloepiphyseal Dysplasia Congenita.- 6.1.2 Spondyloepiphyseal Dysplasia Tarda.- 6.2 Pseudoachondroplasia.- 6.3 Diastrophic Dysplasia.- 6.4 Metatropic Dysplasia.- 6.5 Spondylometaphyseal Dysplasia.- 6.6 Other Disorders.- 6.6.1 Parastremmatic Dysplasia.- 6.6.2 Dyggve-Melchior-Clausen Syndrome.- 6.6.3 Kniest Dysplasia.- 7. Generalised Decrease in Bone Density.- 7.1 Osteogenesis Imperfecta.- 7.1.1 Osteogenesis Imperfecta Congenita.- 7.1.2 Osteogenesis Imperfecta Tarda.- 7.2 Idiopathic Osteolysis.- 8. Increased Bone Density.- 8.1 Osteopetrosis.- 8.1.1 Autosomal Recessive Form.- 8.1.2 Autosomal Dominant Form.- 8.2 Pycnodysostosis.- 9. Craniotubular Dysplasias and Hyperostoses.- 9.1 Craniometaphyseal Dysplasia.- 9.2 Metaphyseal Dysplasia (Pyle Disease).- 9.3 Diaphyseal Dysplasia (Camurati-Engelmann).- 9.4 Infantile Cortical Hyperostosis.- 9.5 Other Craniotubular Disorders.- 9.5.1 Endosteal Hyperostosis.- 9.5.2 Sclerosteosis.- 9.5.3 Frontometaphyseal Dysplasia.- 9.5.4 Craniodiaphyseal Dysplasia.- 10. Cranio-Facial Abnormalities.- 10.1 Cranio-Facial Dysostosis (Crouzon Syndrome).- 10.2 Acrocephalosyndactyly (Apert Syndrome).- 10.3 Acrocephalopolysyndactyly (Carpenter Syndrome).- 10.4 Mandibulofacial Dysostosis (Treacher Collins Syndrome).- 11. Vertebral Anomalies.- 11.1 Klippel-Feil Syndrome.- 11.2 Costovertebral Segmentation Anomalies.- 11.3 Sprengel Deformity.- 12. Limb and Digital Anomalies.- 12.1 Limb Reduction.- 12.2 Synostosis Syndromes.- 12.2.1 Radioulnar Synostosis.- 12.2.2 Humero-radial Synostosis.- 12.2.3 Tarsal Synostosis.- 12.3 Digital Anomalies.- 12.3.1 Polydactyly.- 12.3.2 Syndactyly.- 12.3.3 Symphalangism.- 12.3.4 Brachydactyly.- 12.3.5 Ectrodactyly.- 13. Mucopolysaccharidoses and Other Storage Disorders.- 13.1 MPS I-H(Hurler Syndrome).- 13.2 MPS II(Hunter Syndrome).- 13.3 MPS IV(Morquio Syndrome).- 13.4 Gaucher Disease.- 14. Abnormalities of Cartilage and Fibrous Tissue.- 14.1 Diaphyseal Aclasia.- 14.2 Enchondromatosis (Ollier Disease).- 14.3 Neurofibromatosis (Von Recklinghausen Disease).- 14.4 Fibrous Dysplasia.- 14.5 Fibrodysplasia Ossificans Progressiva.- 15. Miscellaneous Disorders.- 15.1 Osteopoikilosis.- 15.2 Melorheostosis.- 15.3 Osteopathia Striata.- 15.4 Cleidocranial Dysplasia.- 15.5 Marfan Syndrome.- 15.6 Homocystinuria.- 15.7 Larsen Syndrome.- 15.8 Chondro-Ectodermal Dysplasia (Ellis-Van Creveld Syndrome).- 15.9 Schwartz Syndrome.- 15.10 Dyschondrosteosis.- 15.10.1 The Madelung Deformity.- 15.11 Mesomelic Dysplasia.

Nomenclature and Terminology

The majority of the inherited skeletal dysplasias are rare, and until recently they have been grouped into general categories rather than delineated into specific disorders. The realisation that the recognition and accurate definition of individual abnormalities facilitates satisfactory management and prognostication, has led to increased efforts towards the separation and precise identification of individual syndromes.