Congenital spondyloepiphyseal dysplasia

This is part of Rare diseases.

Diagnosis: Congenital spondyloepiphyseal dysplasia

Synonyms: Spondyloepiphyseal dysplasia congenita


Publication date: 2013-03-15
Version: 3.1

The disease

Congenital spondyloepiphyseal dysplasia is characterised by severe bone growth abnormalities (spondyl=vertebra, epiphyseal=the end of the long bones, dysplasia=abnormal growth). The condition is hereditary and is part of a group of disorders known as skeletal dysplasias.

Disorders of skeletal development, or skeletal dysplasias, cause bone abnormalities and deformities. The severity of the deformities increases as the child grows and gains weight. Some skeletal dysplasias affect the whole skeleton while others affect certain areas, like the ends of the long bones or the growth zones (tmetaphysis). Abnormalities can affect bone, cartilage or connective tissue, and individuals with skeletal dysplasia are usually of short stature.

More than 200 inherited skeletal dysplasias are currently recognised. Information on several of them, including achondroplasia, diastrophic dysplasia, pseudo-achondroplasia, multiple epiphyseal dysplasia, and late-onset spondyloepiphyseal dysplasia, is available in the Rare Disease Database of the Swedish Board of Health and Welfare.


In Sweden, 1-2 children with congenital spondyloepiphyseal dysplasia are born every year. There are approximately 20-30 individuals with the disorder in Sweden.


Congenital spondyloepiphyseal dysplasia is caused by a mutation (a structural defect) in a gene known as COL2A1 on chromosome 12 (12q13.11-13.12). This gene governs the production of (codes for) type II collagen. The mutation impairs the development of bone, cartilage, and connective tissue, and normal bone growth is disrupted. This results in short stature, progressive spinal deformities and joint problems. Since collagen II is also present in the eye, the mutation may also cause defects in the vitreous body, resulting in myopia (short-sightedness).


The inheritance pattern of congenital spondyloepiphyseal dysplasia is autosomal dominant. This means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disease and do not pass it down.

Figure: Autosomal dominant inheritance

In most children the disorder is caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with this mutation risks passing on the mutated gene to his/her children.


The average length of newborn children with congenital spondyloepiphyseal dysplasia is 35 cm, as compared with the normal average of 50 cm. The trunk and neck are particularly short, but the upper arms and the femurs (thigh bones) are also disproportionately small. Many children are born with club foot (of the drop foot type), and hip dislocation (luxation). The musculature is weak and floppy, and trunk muscles are underdeveloped. Many infants die shortly after birth owing to severe respiratory distress.

Cleft palate is common. The facial profile is often flat and the eyes wide set (hypertelorism). The chest is underdeveloped, abnormally soft and barrel-shaped. Intellectual development is completely normal, but skeletal development and motor skills are delayed. Walking is delayed and the child will have a waddling gait. Knock-knees or bow-legs are common. Spinal defects may present as early as in infancy, and tend to progress over the years. It is often difficult to extend the hips, knees, and elbows, which may become increasingly stiff. Hip joint deformities and premature arthritis often cause considerable disability from an early age. Adults with congenital spondyloepiphyseal dysplasia reach a final stature of 85 to 140 cm.

The neck is short with flattened cervical vertebrae. The tooth-like projection on the upper side of the second cervical vertebra (the dens axis), is sometimes underdeveloped. This may result in increased pressure on the spinal cord, which, in some cases, can lead to progressive leg paralysis. The first signs of spinal cord injury are often subtle and easily overlooked. They include diffuse leg pain, fatigue, decline in physical function, and failure to walk, despite normal development in other respects.

Before surgery under general anaesthesia the anaesthetist must be informed about the condition, as there may be complications associated with intubation (when a tube is inserted into the airways to facilitate breathing during surgery), as the head is forced back during this procedure. Surgery should always be preceded by X-ray examination of the cervical column.

Pronounced congenital myopia is common. Children with congenital spondyloepiphyseal dysplasia sometimes also have strabismus (squinting), congenital cataracts, glaucoma and retinal detachment.

Infections of the middle ear are frequent among individuals with congenital spondyloepiphyseal dysplasia, and may lead to hearing impairment if left untreated.

As the mobility of the major joints decreases, motor functions progressively decline. A wheelchair may be needed, even before adulthood.


Skeletal dysplasia is usually evident at birth. In some cases the condition has been discovered in a routine ultrasound during pregnancy. Skeletal dysplasias are a complicated group of disorders in terms of both diagnosis and treatment. As treatment regimes, patterns of inheritance, and prognoses differ, it is essential to establish a correct diagnosis.

Usually diagnosis can be made at birth, based on observation of symptoms typical of the disease, and an X-ray of the skeleton. The diagnosis can frequently be confirmed by DNA analysis of a blood sample. At the time of diagnosis the family should be offered genetic counselling. Carrier and prenatal diagnostics, as well as pre-implantation genetic diagnostics (PGD) in association with IVF (in vitro fertilization), are available in families where the mutation is known.


There is no cure for congenital spondyloepiphyseal dysplasia, but a great deal can be done to provide support and compensate for disabilities.

Club foot is evident at birth. The condition can usually be treated with a corrective foot orthosis or a plaster cast, but surgery is sometimes necessary.

An ophthalmologist should examine the child at an early stage. Congenital cataracts are treated surgically. Glaucoma is treated with eye drops to relieve pressure, but may sometimes require surgical intervention. Strabismus is treated by placing a patch over the healthy eye in order to train the squinting eye. Most children need eyeglasses.

Recurrent middle ear infections can be treated by inserting a plastic tube into the eardrum in order to divert fluids and prevent hearing impairment.

Hip joint defects and arthrosis sometimes require surgical intervention. Spinal defects are treated with a corset brace, but may require surgery.

As even minor clefting can cause feeding problems, a thorough examination of the palate and palatal function should be carried out at an early stage. Clefting requires surgical repair. This procedure is performed by a plastic surgeon and is carried out in several stages. Parents of children who have problems sucking and eating require early contact with a dietician and a speech therapist to establish good feeding routines.

Early contact should be established with a habilitation team to stimulate the child’s development as much as possible and help compensate for disabilities. A habilitation team includes professionals with special expertise in different aspects of the disability and how it affects everyday life, health and development. Support and treatment are offered within the medical, educational, psychological, social and technical fields. All interventions focus on the existing needs of the child and family, and are adjusted as the child grows older. Habilitation is carried out in collaboration with individuals close to the child and includes evaluation, treatment, assessing the need for aids, information about the disability, and counselling.

Children and young people of short stature are to be treated age-appropriately and like their peers. Parents should be offered contact with other parents of children of short stature, and the children themselves should also be offered the opportunity to meet children in the same situation. Children and parents may also need to meet adults of short stature to learn more about their situation. Psychological support adapted to age and maturity should be available continuously while the child is growing up.

As most individuals with congenital spondyloepiphyseal dysplasia experience severe joint problems, the child’s immediate environment should be adapted to try to prevent any damage. The habilitation team can give advice on how strain on the joints can be alleviated. Adaptations to the environment make it possible for children to develop their independence. Examples of these adaptations can include door openers, low-hung coat hangers, chairs with footrests and low handrails, handles and light switches. Outdoors, mobility is easier on flat, smooth surfaces, such as asphalted ground. Special orthopaedic shoes or other aids may be needed. Some children require physical therapy and motor training. To prevent hand injuries resulting from excess strain, it is often beneficial to use an electric wheelchair. Later on a specially adapted car may be helpful.

Adults with the disorder may require continued individual habilitation and support in their daily lives. Adjustments to accommodation and the working environment are often essential.

In pregnancy, women with congenital spondyloepiphyseal dysplasia should be in contact with specialist maternity care services. Many of these women experience increasing breathing difficulties. Early delivery by caesarean section two to four weeks before the due date is often necessary.

Occupational guidance is needed, as well as adjustments to the work environment. The employment services and the Swedish Social Insurance Agency can provide information and support.

Practical advice


National and regional resources in Sweden

Diagnostics is performed at regional hospital paediatric clinics. If the diagnosis is inconclusive, investigations can be carried out at the National Centre for Skeletal Dysplasias, located at Uppsala University Children’s Hospital where the Swedish Centre for Deformities and Syndromes is also located. Both these centres also coordinate interventions for children and adults.

The skeletal dysplasia team at the Astrid Lindgren Children’s Hospital has wide experience of monitoring children and young people with skeletal dysplasia. The team consists of representatives from the following areas: respiratory physiology, neurosurgery, neuroradiology, skeletal radiology, paediatric orthopaedics, paediatric endocrinology, physiotherapy, urinary incontinence therapy and clinical genetics. Contacts are research nurse Lo Neumeyer, tel: +46 8 517 775 81, and chief physician Lars Hagenäs, Astrid Lindgren’s Children’s Hospital, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Resource personnel

Professor Göran Annerén, The Rudbeck Laboratory, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 59 42, fax: +46 18 55 40 25.

Associate Professor Lars Rehnberg, Paediatric Orthopaedic Unit, Astrid Lindgren Children’s Hospital, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 777 00.

Chief physician Lars Hagenäs, Paediatric Endocrinology Laboratory, The Astrid Lindgren Children’s Hospital, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Courses, exchanges of experience, recreation

Uppsala University Children’s Hospital arranges special theme days for children with skeletal dysplasia and their parents.

Family camps and other events are arranged by the RBU working group for people with short stature (see under “Organizations for the disabled/patient associations”).

The Association for People of Short Stature in Sweden-DHR, arranges theme days (see under “Organizations for the disabled/patient associations”).

Organizations for the disabled/patient associations etc.

The Association for People of Short Stature in Sweden-DHR, chair Gunilla Hyltén-Cavallius, Södra Forsåkersgatan 44, SE-431 63 Mölndal, Sweden. Tel: +46 31 27 45 74, email: info@fkv.se, www.fkv.se.
The association is in contact with similar organisations in several countries and cooperates closely with associations in the Nordic countries.

RBU, The Swedish National Association for Disabled Children and Young People, St Eriksgatan 44, Box 8026, SE-104 20 Stockholm, Sweden. Tel: +46 8 677 73 00, fax: +46 8 677 73 09, email: info@rbu.se, www.rbu.se.

Courses, exchanges of experience for personnel

Uppsala University Children’s Hospital arranges special theme days for children with skeletal dysplasia and their parents.

Research and Development

There is ongoing clinical and DNA-based research about skeletal dysplasias at Uppsala University Hospital.

Information material

An information leaflet on congenital spondyloepiphyseal dysplasia summarising the information in this database text is available free of charge from the Publishers Department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2012-8-22). Address: SE-106 30 Stockholm, Sweden. Fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se, or tel: +46 75 247 38 80. Postage will be charged for bulk orders.

The booklet “Barn och ungdomar med kortväxthet” (1999). (Children and adolescents with short stature. In Swedish only). Order from RBU (see under “Organizations for the disabled/patient associations”). It can also be downloaded from: www.rbu.se.

Kort men inte liten (In Swedish only). A fact book about short stature by Pernilla Gesén, Eva Schreiber and Ulla-Karin-Karlsson. Order from the Association for People of Short Stature in Sweden-DHR (see under “Organizations for the disabled/patient associations”).

Mindre vanliga människor (1996). A book by and about individuals with growth restriction disorders (in Swedish only). Published by Utbildningsförlaget Brevskolan on behalf of the Association for People of Short Stature in Sweden-DHR (see under “Organizations for the disabled/patient associations”). Edited by Gerd Andersson, Rune Larsson and Eva Schreiber.


Chan D, Rogers J, Bateman JF, Cole WG. Recurrent substitutions of arginine 789 by cysteine in pro-alpha 1(II) collagen chains produce spondyloepiphyseal dysplasia congenita. J Rheum 1995; Suppl 43: 37-38.

Chan D, Taylor TKF, Cole WG. Characterization of an arginine 789 to cysteine substitution in alpha-1(II) collagen chains of a patient with spondyloepiphyseal dysplasia. J Biol Chem 1993; 268: 15238-15245.

Chitty LS, Tan AW, Nesbit DL, Hall CM, Rodeck CH. Sonographic diagnosis of SEDC and double heterozygote of SEDC and achondroplasia – a report of six pregnancies. Prenat Diagn 2006; 26: 861-865.

Cui YX, Xia XY, Bu Y, Zhou GH, Shi YC, Pan LJ et al. Rapid molecular prenatal diagnosis of spondyloepiphyseal dysplasia congenita by PCR-SSP assay. Genet Tes 2008; 12: 533-536.

Dreyer SD, Zhou G, Lee B. The long and the short of it: developmental genetics of the skeletal dysplasias. Clinical Genetics 1998; 54: 464-473.

Escobar LF, Bixler D, Weaver DD, Padilla L-M, Golichowski A. Bone dysplasias: The prenatal diagnostic challenge. Am J Med Genet 2005; 36: 488-494.

Givon U, Kumar SJ, Scott CI Jr. Involvement of the humerus in two generations with spondyloepiphyseal dysplasia. Clin Orthop 1999; 366: 174-177.

Gustavson K-H, Annerén G, Axelsson O, Eriksson L, Gustafsson J, Lönnerholm T, Rhenberg L. Skelettdysplasi. Läkartidningen 1992; 38: 3425-3430.

Hall CM. International nosology and classification of constitutional disorders of bone (2001). Am J Med Genet 2002; 113: 65-77.

Hamidi-Toosi S, Maumenee IH. Vitreoretinal degeneration in spondyloepiphyseal dysplasia congenita. Arch Ophtal 1982; 100: 1104-1107.

Jagell S, Gustavson K-H. Skelettdysplasi hos barn kan ge allvarliga komplikationer. Läkartidningen 1984; 81: 2157.

Liao EY, Peng YQ, Zhou HD, Mackie EJ, Li J, Hu PA et al. Spondyloepihyseal dysplasia tarda with progressive arthropathy. Hum Genet 2004; 115: 74.

Macpherson RI, Wood BF. Spondyloepiphyseal dysplasia congenita. Pediatr Radiol 1980; 9: 217-224.

Nishimura G, Fukushima Y, Aihara T, Ohashi H, Nishimoto H, Nishimura J. Previously undescribed spondyloepiphyseal dysplasia associated with craniosynostosis, cataracts, cleft palate, and mental retardation: report of four sibs. Am J Med Genet 1998; 77: 1-7.

Shetty GM, Song HR, Lee SH, Kim TY. Bilateral valgus-extension osteotomy of hip using hybrid external fixator in spondyloepiphyseal dysplasia: early results of a salvage procedure. J Pediatr Orthop B 2008; 17: 21-25.

Sulko J, Czarny-Ratajczak M, Wozniak A, Latos-Bielenska A, Kozlowski K. Novel amino acid substitution in the Y-position of collagen type II causes spondyloepimetaphyseal dysplasia congenita. Am J Med Genet A 2005; 137: 292-297.

Xia XY, Cui YX, Huang YF, Pan LJ, Feng Y, Yang B et al. Molecular prenatal diagnosis in 2 pregnancies at risk for spondyloepiphyseal dysplasia congenita. Clin Chim Acta 2008; 387: 153-157.


OMIM (Online Mendelian Inheritance in Man)
Search: spondyloepiphyseal dysplasia, congenital type

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert Professor Karl-Henrik Gustavson, Uppsala University Hospital, wrote the draft of this information material.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Publication date: 2013-03-15
Version: 3.1
Publication date of the Swedish version: 2013-01-11

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se


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This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.