eMedicine Specialties > Orthopedic Surgery > Neoplasms

Diastrophic Dysplasia

Author: Shital Parikh, MD, Assistant Professor, Department of Pediatric Orthopaedic Surgery, Cincinnati Children's Hospital Medical Center
Coauthor(s): Preeti Batra, MBBS, MD, Staff Physician, Department of Radiology, VS Hospital, India; Twee Do, MD, Assistant Professor, Department of Pediatric Orthopedic Surgery, University of Cincinnati College of Medicine; Director, Neuromuscular Orthopedic Services, Cincinnati Children's Hospital Medical Center
Contributor Information and Disclosures

Updated: Jan 29, 2009

Introduction

Skeletal dysplasias are a heterogeneous group of dysplasias that include more than 200 recognized conditions (see examples in images below). They are disorders of growth and remodeling of bone and cartilage. Most disorders result in short stature, which is defined as height more than 2 standard deviations below the mean for the population at a given age.

Problem

Conditions that cause dwarfing are frequently referred to as short-limb or short-trunk types, depending on whether the trunk or limbs are more extensively involved. Diastrophic dysplasia is considered a short-limb dwarfing condition. Additional terms used to describe the segment of the limb with the greatest involvement are rhizomelic (proximal), mesomelic (middle), and acromelic (distal). In diastrophic dysplasia, the extremity involvement is rhizomelic (in 40% of cases) or mesomelic (in 29% of cases), as seen in the image below.

A distinct group of patients who have many features of diastrophic dysplasia are referred to as having diastrophic variants; these individuals are taller and less severely affected than persons with classic diastrophic dwarfism. Classic diastrophic dysplasia and diastrophic variants are different expressions of a single genetic disorder (with variable penetrance) rather than separate entities. Individuals identified as having a diastrophic variant should be referred to as having mild diastrophic dysplasia.

Impairment of physeal, epiphyseal, and articular cartilage throughout the body is responsible for characteristic findings. Unlike those with achondroplasia or hypochondroplasia, patients with diastrophic dysplasia have epiphyseal involvement and are at risk for degenerative joint disease. Although the development and growth of cartilaginous structures are disturbed, the intramembranous ossification and appositional growth pattern are not primarily affected.

Frequency

Although diastrophic dysplasia is extremely rare, the percentage of carriers in certain groups is high. In Finland, 1-2% of the general population are carriers and a total of 183 cases have been diagnosed, with a prevalence of 1 per 30,000 population. Diastrophic dysplasia has been observed in most white populations.

Diastrophic dysplasia is an autosomal recessive disorder and occurs with equal frequency in males and females.

Etiology

In 1994, Hastbacka et al identified the gene DTDST. This gene, which codes for a sulfate transporter protein, has been mapped to distal end of chromosome bands 5q31-q34.⁴

DTDST is inherited in an autosomal recessive manner.⁵ About 5% of cases may involve sporadic new mutations. Both parents of an affected individual are carriers of the abnormal gene but are clinically healthy. For a carrier couple, each pregnancy entails a 25% risk of producing an affected child. Each unaffected full sibling of an affected individual has a 67% likelihood of being a carrier. The offspring of an affected individual is a carrier and therefore unaffected unless the other parent is a carrier or affected with the same condition. Diastrophic dysplasia and McKusick-type metaphyseal chondrodysplasia are the only skeletal dysplasias with autosomal recessive transmission.

Diastrophic dysplasia is a disorder with a wide range of clinical manifestations; this variation has important implications. Parents of a child with mild diastrophic dysplasia, which would previously have been called a diastrophic variant, must be informed that they are at 25% risk of having other children with disproportionate dwarfism. In addition, they should be made aware that the expression of the disorder may be more severe in subsequent children.

Pathophysiology

Proteoglycans are considered to be among the chief constituents of cartilage. Undersulfation of proteoglycan in the cartilaginous matrix is responsible for the impairment of performance and load-bearing ability of physeal, epiphyseal, and articular cartilage throughout the body.

The DTDST protein acts as a sodium-independent sulfate/chloride transporter and belongs to the SLC26 anion transporter family. The Finnish founder mutation in DTDST has been identified.⁴ Approximately 95% of affected Finnish patients have a rare ancestral haplotype that was found in only 4% of a Finnish control population. The founder mutation is a guanine-thymine (GT) to guanine-cytosine (GC) transition in the splice donor site of a 5'-untranslated exon of the DTDST gene. The mutation acts by severely reducing levels of mRNA of the DTDST transcript.⁶

Mutations in DTDST are responsible for a family of chondrodysplasias that include 4 recessively inherited conditions: diastrophic dysplasia, multiple epiphyseal dysplasia, atelosteogenesis type 2, and achondrogenesis type 1B. In addition to the intrinsic sulfate transport properties of the DTDST protein, other factors influence the phenotype in individuals with these mutated alleles.

Presentation

In evaluating a patient, several aspects of his or her medical history should be investigated for coordination of care. Respiratory difficulties, neurogenic problems, family history, and history of any prior skeletal surgery should be investigated.

The diagnosis can be made at birth with the observation of pathognomic features or within the first few months of life, when the cystic swelling of the ears becomes apparent. Neonates with diastrophic dysplasia may be thought to have atypical achondroplasia at birth, but the diagnosis is relatively easy to establish in the older child or adult because of the unique combination of deformities. Birth length, head circumference, and weight should be recorded. The mental status and intelligence findings are normal.

Height is related to severity of involvement; taller people are less severely affected than shorter people. The mean height is 136 cm in men and 129 cm in women. The pubertal growth spurt is diminished; therefore, the overall growth failure is progressive. The other components of puberty occur normally. This fact suggests that the bones do not respond to hormonal influences. The patient's height percentile for age should be determined by using specific growth charts. In relationship to trunk length, the limbs are relatively short. Short-limbed stature can be confirmed by measurement of the upper-to-lower segment ratio. The normal ratio is 1.6 at birth and decreases to 0.93 during adolescence. Kyphoscoliosis and hip and knee contractures further accentuate the apparent dwarfism. Difficulty in walking is common, and some patients are wheelchair bound.^7,8

The expression and severity of diastrophic dysplasia vary greatly. Patients may present with complaints pertaining to the head and neck, spine, major joints, and hands and feet, as seen in the image and described below.

Head and neck

Typical facial features are present in most patients.⁹ Prominent cheek and circumoral fullness inspired the historical term cherub dwarf. The nasal bridge is narrow, without flattening or depression. Because the eyes are normally spaced, the distance between the bridge of the nose and inner canthus of the eye appears to be increased. In contrast to the bridge, the mid nose is broad. The nostrils flare, and the columella dips low between them. The arch of the palate is wide, and many teeth are visible when the patient smiles. The face has a long, full appearance with a high, broad forehead and square jaw. Midline hemangiomas are sometimes present but fade with age.

Approximately 50% of patients have a cleft palate, either complete or partial. Other abnormalities, such as a high and arched palate, bifid uvula, or submucous clefts, are common. This cleft palate may also contribute to aspiration pneumonia. The cartilage of the larynx and trachea is abnormally soft, and this may contribute to narrowing of respiratory passages. The abnormal palate may play a part in the production of the somewhat characteristic voice heard in patients with this condition. Patients also have a hoarse cry. Hyponasality or misarticulation of R, S, or L sounds is observed in 50% of these patients, possibly due to defects in the palate or vocal cords or due to laryngeal cartilage affection in a process similar to that seen in the ears.¹⁰

The pinnae, though unaffected at birth, develop acute swelling at 3-6 weeks of age, as seen in the image below. The swelling is usually bilateral. The pinnae are reddened, swollen, hot, and often fluctuant; they may feel cystic. After these findings resolve, the cartilage thickens and deforms, giving rise to cauliflower ear, one of the pathognomonic features of diastrophic dysplasia. This typical cauliflower ear is present in 85% of patients. Eventually, the pinnae may become calcified or even ossified. Typically, older patients have rock-hard masses in the superior portions, which are easily palpable.

Spine

One half to one third of patients develop cervical kyphosis. Cervical kyphosis may be present in infancy; its course is variable. Though spontaneous resolution has been reported, the possibility of progression with neurologic involvement should always be considered. Progressive kyphosis of the cervical spine causing quadriplegia with respiratory muscle paralysis and neurogenic bladder has been described in young children.^{11,12,13,14,15,16}

Generally, external signs of cervical abnormalities are absent; however, 80% of patients present with some degree of spinal curvature. Scoliosis is not present at birth, but it tends to develop within the first year of life; it becomes progressively severe with weight bearing. Spinal stenosis is not common, in contrast to its presence in achondroplasia. Mild stenosis may be masked by a patient's relative inactivity. Most patients have significant lumbar lordosis, most likely due to associated hip flexion contracture. Kyphoscoliosis can cause imbalance of the trunk, leading to difficulties in gait and a reduction in already short standing height.

Early and rapid progression of spinal degenerative changes is a normal finding in patients, regardless of age, and leads to stiffness of the cervical spine on physical examination. At present, only one case of atlantoaxial instability has been reported, to the authors' knowledge.

Scoliosis is common. The reported prevalence is 37-88%. Scoliosis can be divided into 3 subtypes: early progressive, idiopathic, and mild nonprogressive, as seen in the first image below. In early progressive scoliosis, dysplastic curves are sharply angular and segment curves are short with associated kyphosis at the same level. Neurologic deficits may be present from severe kyphosis. Lumbar lordosis is usually significant, as seen in the second image below. Spinal stenosis is less common. Degenerative changes are common at all levels, and in patients of all ages. These changes lead to spinal stiffness that is evident on clinical examination.

The hips maintain a persistent flexion contracture. Patients may present with hip subluxation. Arthritic changes develop by early-to-middle adulthood. Hip dysplasia is usually progressive and may result in a significant decrease in the range of motion.¹⁷ The knees, too, have flexion contractures. Excessive valgus with lateral dislocation of the patella may occur. Genu valgum with patellar dislocation may occur in patients with diastrophic dysplasia. Genu varum is uncommon. Similar to hip changes, arthritic changes develop by early-to-middle adulthood. Rarely, the patient may manifest joint laxity and instability rather than limitation of motion. The symptoms may involve hips, knees, ankles, shoulders, or elbows.¹⁸

In the major joints, motion is markedly limited, and there is a tendency toward dislocation or subluxation. The hips, knees, and elbows are usually affected. At birth, the hips are normal, but with walking, coxa vara becomes apparent, often with subluxation or dislocation of the femoral heads. Bilateral hip dislocations occur in 25% of patients. The proximal femoral epiphyses deform. Hinge abduction may develop in some patients. Valgus may develop at the knee joint, along with subluxation of the patella and flexion contracture. The elbows and shoulders are occasionally subluxated, and the radial head may be dislocated. Degenerative joint disease of the hips and knees develops in early-to-mid adulthood. The joints may be affected by webbing, in addition to the contractures.

Hands and feet

The hands are short, broad, and ulnarly deviated due to shortening of the ulna. The fingers appear widely spaced. About 95% of patients have an abducted, hypermobile, hitchhiker thumb, as seen in the image below. The first metacarpal is characteristically short, leading to the clinical appearance of proximal insertion of the thumb. Flexion is absent at multiple proximal interphalangeal joints of the fingers. This finding, termed symphalangism, is associated with the absence of normal flexural creases and suggests an antenatal onset.

Other findings

Associated hernia is another possible manifestation of the basic mesodermal defect. Cases of inguinal hernia have been reported in patients with diastrophic dysplasia.

Differential diagnoses for diastrophic dysplasia are as follows:

• Achondroplasia
• Spondyloepiphyseal dysplasia
• Hypochondroplasia
• Cartilage hair hypoplasia
• Chondroectodermal dysplasia (Ellis-van Creveld syndrome)
• Chondrodysplasia punctata (Conradi disease)
• Pseudodiastrophic dysplasia
• Metatropic dwarfism
• Thanatophoric dwarfism
• Osteogenesis imperfecta
• Asphyxiating thoracic dystrophy
• Hypophosphatasia
• Arthrogryposis multiplex congenita
• Larsen syndrome

Consultations should involve the following specialists:

• Otolaryngologist: Cleft palate and laryngeal abnormalities should be identified and treated early in life.
• Geneticist: A clinical geneticist may be of help in counseling the family. A geneticist may also be a valuable resource for the pediatrician seeking additional information or consultation. The proper establishment of the mode of inheritance not only aids in genetic counseling but also enables the orthopedist to distinguish diastrophic dwarfism from other forms of dwarfism.
• Pulmonologist: Pulmonary function should be evaluated, and respiratory complications such as hypopnea and cyanosis should be prevented.
• Pediatrician: The American Academy of Pediatrics and the Committee on Genetics have issued guidelines to assist the pediatrician in caring for children with dwarfism and in advising their families. Occasionally, the pediatrician is asked to advise pregnant women who have been informed of a prenatal diagnosis of diastrophic dysplasia.

Indications

In a large survey of patients with chondrodysplasias, the highest percentage of patients treated surgically were those with diastrophic dysplasia (87.5%). As a part of the same survey, 88.8% of patients judged the outcome after surgery to be an improvement. See Surgical therapy for a discussion of the relevant surgical procedures.

Relevant Anatomy

See Clinical.

Contraindications

See Surgical therapy.

• Search for CME/CE on This Topic »

• Multiple Epiphyseal Dysplasia (Orthopedic Surgery)
• Arthrogryposis (Pediatrics: Genetics and Metabolic Disease)
• Achondrogenesis (Pediatrics: Genetics and Metabolic Disease)
• Skeletal Dysplasia (Pediatrics: Genetics and Metabolic Disease)