Diastrophic Dysplasia

The term "diastrophic" is Greek and means "crooked". Although diastrophic dysplasia occurs in most countries, the highest prevalence is found in Finland (1 in 33,000) where the carrier rate in the population is 1 – 2% (3). The incidence in non-Finnish populations is considerably lower, being 1 in 500,000 live births (6).

 
How Diastrophic Dysplasia Is Inherited

Diastrophic dysplasia is inherited as an autosomal recessive trait, with very wide variability of phenotypic expression. Approximately 5% of cases constitute new mutations (6).

 
Causes of Diastrophic Dysplasia

Diastrophic dysplasia is caused by a mutation in the gene coding for a sulfate transporter protein that is essential for normal cartilage function. This protein is called DTDST and was first identified by Hastabacka and colleagues in 1994 (1). The gene is located on chromosome 5 (5q31-q34). Mutations in the same gene are responsible for lethal chondrodysplasias.

Proteoglycans are complex molecules that absorb water and facilitate load bearing in articular cartilage. Reduction in sulfate transporter concentrations in chondrocytes causes under-sulfation of the proteoglycan matrix and predisposes individuals to early degenerative joint disease. Diastrophic dysplasia affects chondrocyte function in the growth plate, epiphyseal region and other areas such as the trachea.

 
Physical Characteristics

The physical characteristics of diastrophic dysplasia include a short limbed form of disproportionate short stature. Both joint dislocations and joint contractures can be present. Intelligence is typically average.

Face & Skull
  • Narrow nasal bridge and broad midportion of the nose
  • Long and broad philtrum
  • High, broad forehead
  • Square jaw
  • Cleft palate in approximately 50% of children
  • Capillary hemangiomas called an "Angel's kiss" can be present in the midforehead region. They will disappear or fade with time.
  • In the majority of patients in first 2 weeks of life, cystic swellings of the ear appear but resolve spontaneously, resulting in the characteristic “cauliflower ear” deformity.
Trunk, Chest, & Spine:
Arms & Legs:
  • Shortening of limbs
  • "Hitchhiker’s thumb." Due to poor development of the bone supporting the thumb, the main thumb joint deviates outwards
  • Limited movement of the fingers due to symphalangism
  • Dislocations of the elbow and shoulder
  • Dislocated kneecap
  • Clubfoot
  • Abnormal gait
  • Weight bearing on balls of feet and toes with compensatory knee and hip flexion
What are the X-ray characteristics?

The radiographic features of Diastrophic Dysplasia include short and broad long bones of the limbs. The metaphyses are flared and crescent-shaped, and flattened epiphyses are typical. The epiphyses of the proximal tibias are triangular and larger than those of the distal femoral epiphyses. The metacarpals, metatarsals, and phalanges are deformed and shortened. Cervical kyphosis and thoraco-lumbar kyphoscholiosis are characteristic at different ages. There is a moderate narrowing of the interpediculate distances within the lower lumbar segments of spine. The hips are either partially or completely dislocated.

 
Making the Diagnosis

The condition is typically recognized at birth based on physical and radiographic evaluation. Milder variants or atypical cases may not be diagnosed until a later age. If suspicions arise during a prenatal ultrasound, molecular testing can be done from an aminocentesis sample.

In parents who already have children with diastrophic dysplasia, an ultrasound scan or molecular genetic testing (using DNA from amniocentesis or chorionic villus sampling) in the first trimester of pregnancy offers the possibility of prenatal diagnosis of this condition.

 
Musculoskeletal Problems
Cervical Spine

Cervical kyphosis is present in 30 – 50% of individuals. It is due to hypoplasia of the vertebral bodies and progressive degenerative changes in the intervertebral joints. Kyphosis can be sufficiently severe and will cause a predisposition to spinal cord compression and quadriplegia (weakness of all 4 extremities and incontinence). Short, sharply angulated curves are associated with severe kyphosis and increase the incidence of neurological abnormalities. Surgery may be necessary to alleviate the spinal cord compression in the neck. A halo and vest device is usually employed after surgery to support the neck until stable fusion is achieved. Occasionally, the kyphosis will resolve spontaneously.

Thoracolumbar Spine

Scoliosis, although not apparent at birth, will become severe as weight bearing increases. The curves usually develop around 5 years of age but can develop even before walking age. The spine curvature causes trunk deformity and barrel chest. Three distinct patterns of scoliosis occur: early progressive, idiopathic-type and mild non-progressive. Kyphoscoliosis occurs frequently (up to 90% of patients) in the lumbar region of the spine. Lumbar lordosis is increased due to exaggerated thoracic kyphosis and concomitant hip flexion contractures (hip joint is fixed with the thigh bent forwards).

Severe Clubfoot

Severe clubfoot is almost always present and typically requires surgical release. Surgery is usually undertaken around 1-year of age, to enable the child to start walking. In spite of early intervention, recurrence of the foot deformity is common and an osteotomy may become necessary. Special shoes are oftentimes required.

Progressive Sublixation

Progressive subluxation of the hips occurs because the soft articular cartilage is unable to perform its normal function of load bearing. Superimposed joint contractures around the hips and knees lead to restricted movement and deformity. If the deformity interferes with walking, an osteotomy is performed around the hips or knees. Due to the intrinsic cartilage abnormality, degenerative joint disease (arthritis) is common. Flexion deformities are pronounced. Knees are dislocated. Hip or knee replacement surgery is usually necessary in early to mid-adult life and typically has successful results.

 
Problems Elsewhere in the Body
Respiratory Obstruction

Respiratory obstruction, including laryngeal stenosis, may occur in newborns. The mortality rate due to respiratory distress can approach 25% in early infancy.

Hypoplastic Cartilage

Hypoplastic cartilage in the trachea and larynx causes voice abnormalities and breathing difficulty.

Small Auditory Canals

Small auditory canals are characteristic, but this does not usually impair hearing. However, deformity of the middle ear ossicles can result in
hearing loss.

 
What to Look For

In infancy, it is important to be regularly monitored by a pediatric orthopedic surgeon so that future problems of the feet and spine can be managed and possibly evaded. Surgery is usually performed before walking age to correct foot deformities.

Later in life, patients must look out for worsening foot deformities, progressive curvature of the spine, and hip pain in early adult life (due to arthritis). Common surgical procedures intended to correct these problems include an osteotomy of the foot or lower leg (to achieve a plantigrade foot) or hip replacement surgery (for progressive degenerative arthritis).

Occasionally, spinal cord compression in the neck can lead to quadriparesis, resulting in a loss of limb function. Symptoms to watch for include a loss of walking or reduced endurance, altered sensations in the arms and legs, or incontinence. Oftentimes patients undergo spinal fusion surgery in the neck or lower back, along with decompression of the spinal cord.

Generally all skeletal dysplasias warrant multidisciplinary attention. Regular assessment by an orthopedist, geneticist, pediatrician, dentist, neurologist, and physical therapist will provide the most comprehensive treatment.

 
References
  1. Hastbacka, J.; Sistonen, P.; Kaitila, I.; Weiffenbach, B.; Kidd, K. K.; de la Chapelle, A. : A linkage map spanning the locus for diastrophic dysplasia (DTD). Genomics 11: 968-973, 1991.
  2. Jones, Kenneth L. Recognizable Patterns of Human Malformation. Philadelphia, PA: Elsevier Saunders. 2006.
  3. Poussa, Mikko. Merikanto, Juhani. Ryoppy, Soini. Marttinen, Eino. Kaitila, Ilkka. The Spine in Diastrophic Dysplasia. Spine; 16(8):881-887. 1991.
  4. Scott, Charles I. Dwarfism. Clinical Symposium, 1988; 40(1):9-10.
  5. Spranger, Jurgen W. Brill, Paula W. Poznanski, Andrew. Bone Dysplasias: An Atlas of Genetic Disorder of Skeletal Development. Oxford: Oxford University Press. 2002.
  6. Diastrophic Dysplasia Booklet http://pixelscapes.com/ddhelp/DD-booklet/

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