Spondyloepimetaphyseal Dysplasia

Spondyloepimetaphyseal Dysplasia (SEMD) describes a group of disorders which have major radiological abnormalities of the spine, epiphyses, and metaphyses in common. Multiple forms exist and the phenotypes, modes of inheritance, and radiographic abnormalities vary considerably.

Spondyloendochromatosis; Camera Stella Syndrome; Leonard Hughes Syndrome.

Strudwick type of SEMD (Strudwick Syndrome)

• SEMD with Joint Laxity
• SEMD with Micromelia
• SEMD Iraqi type (Sohat type of SEMD)
• SEMD Irapa type
• SEMD type II
• X-linked type of SEMD
• Sponastrime Dysplasia
• SEDM with Short Limbs and Abnormal Calcifications
• SEMD with Multiple Joint Dislocations (Hall type of SEMD)

The incidence for spondyloepimetaphyseal dysplasia remains unknown. However, the overall incidence for all skeletal dysplasias is approximately 1 case per 4000-5000 births in the USA. However, some authors have suggested that the true incidence may be twice as high because many skeletal dysplasias do not manifest clinically until the individual is diasgnosed with short stature, joint symptoms, or other complications that arise during childhood. Lethal skeletal dysplasias are estimated to occur in 0.95 per 10,000 live births. The 4 most common skeletal dysplasias are thanatophoric dysplasias, achondroplasia, osteogenesis imperfecta, and achondrogenesis. Thanatophoric dysplasia and achondrogenesis account for 62% of all lethal skeletal dysplasias. Achondroplasia is the most common nonlethal skeletal dysplasia.

Autosomal dominant inheritance is found in Strudwick type of SEMD and SEMD with Multiple Dislocations. Autosomal recessive transmission occurs in SEMD with Joint Laxity, Iraqi type of SEMD, Irapa type of SEMD, Short Limb-Abnormal Calcification type of SEMD, and Sponastrime Dysplasia. X-Linked SEMD is likely to be inherited in an (X-linked) dominant manner. Inheritance in the Micromelic type of SEDM has not been determined, yet.

Skeletal dysplasias are characterized by abnormal growth of bone and cartilage. Involvement of both the epiphyses and metaphyses distinguishes the Spondyloepimetaphyseal Dysplasias from the Spondylometaphyseal Dysplasias and the Spondyloepiphyseal Dysplasias.

Clinical syndromes with characteristic radiological findings. In utero ultrasonography may identify limb abnormalities but is not diagnostic.

The clinical features depend on the type of SEMD and the age of the patient.

Strudwick type of SEMD presents at birth with cleft palate, short limbs and trunk, protruding abdomen, and respiratory distress secondary to small chest with short ribs. Other clinical features include hypertelorism and a flat face. Intelligence and life expectancy are normal. Features occurring later on in life include severe coxa vara (with possible dislocation), a waddling gait, lumbar hyperlordosis (platyand anisospondyly) and myopia with retinal detachment. Before these children reach school age, the characteristic changes in the metaphyses of the long bones become evident, which usually affect the ulna more severely than radius, fibula, or tibia. The disorder manifests as fragmentation of the long bone metaphyses mixed with areas of sclerosis. Lung function tends to remain compromised, even more so if kyphoscoliosis develops. Cervical spine instability may be present because of hypoplasia of C3 and/or the odontoid process. The genetic defect has been mapped to 12q13, involving the COL2A1 (collagen type II) gene.

SEMD with Joint Laxity is characterized by short stature, mental retardation, joint and ligamentous laxity with dislocations (e.g., hips, radial heads). Kyphoscoliosis is already present at birth, may progress rapidly and lead to significant cardiopulmonary changes (cor pulmonale) and even paraplegia. The face appears oval, often has a long philtrum, and either a high arched palate or a cleft palate. Congenital cardiac lesions (e.g., atrial and/or ventricular septal defects) are common. Ocular features include blue sclerae, myopia, and lens dislocation. This form of SEMD has the highest incidence in South Africa, where it was also first described.

SEMD with Micromelia presents at birth and is characterized with short stature, small thoracic dimensions, and brachydactyly. Mental retardation is common.

SEMD Iraqi type: The name originates from the first family described with this disorder, who was from Iraq. The patients present at birth with short stature, short limbs, and short neck. Generalized joint laxity and varus deformity of the hips and knees are characteristic findings. Hepatosplenomegaly with prominent abdomen is common. The chest is often short and narrow. The vertebrae may be abnormal (platyspondyly, cleft vertebrae), and the interpeduncular distance is decreased.

SEMD Irapa type: This disorder is named after the Indians in Venezuela's Irapa district on the north shore, where it was first detected. Presentation is usually delayed until approximately 5 years of age, when symptoms of joint pain and walking difficulties occur. There is a limited range of movement in affected joints and premature osteoarthrosis and osteoporosis develop. Generalized platyspondyly, widening and shortening of the tubular bones with anomalies of the metaphyses, shortening and occasionally fusion of the metacarpalia, coxa vara and pelvic anomalies (acetabular dysplasia) are the main skeletal findings.

SEMD type II: Usually presents with skeletal features such as shortened legs with bowing of the femurs and tibia. With the exception of short stature, these modelling defects improve spontaneously by the onset of adolescence.

X-Linked type of SEMD: Short stature is present, but becomes usually not evident before the age of 2 years. Radial dislocation of the hands is a typical feature caused by relative elongation of the ulna. Progressive platyspondyly and predominately lumbar narrowing of the interpeduncular distance define the spinal anomalies. Coxa vara is common.

Sponastrime Dysplasia: Less than 20 patients have been reported. This type of SEMD presents early in infancy with short stature and craniofacial dysmorphism including enlarged head with frontal bossing, midface hypoplasia with a short, upturned nose and depressed nasal root. However, microcephaly and mental retardation have also been described in these patients. Progressive lumbar lordosis and kyphoscoliosis may develop and result in cardiopulmonary changes (restrictive lung disease and cor pulmonale). Striation of the metaphyses refers to the irregular, longitudinal sclerotic changes seen on radiographs, most notably in the distal femur and proximal tibia metaphyses. Coxa vara (with potential dislocation) and avascular necrosis of the capital femoral epiphyses have been described. In contrast to most other forms of SEMD, vertebral body size can be enlarged (despite platyspondyly), resulting in increased interpeduncular distance. Subglottic stenosis and tracheobronchomalacia have been reported.

SEDM with Short Limbs and Abnormal Calcifications characterized by short limbs (including short hands and feet), but in contrast to most other forms of SEDM, the trunk is relatively long. Facial dysmorphic features include hypertelorism, midfacial hypoplasia, depressed and wide nasal bridge, and micrognathia. The chest is narrow, and progressive kyphoscoliosis may lead to cor pulmonale. Ligamentous laxity and anomalies of the odontoid process with subluxation of C1 and C2 may cause compression of the cervical cord.

SEMD with Multiple Joint Dislocations: These patients present with short stature, midface hypoplasia, and severe, generalized muscular hypotonia. Almost one-third of these patients has some form of laryngeal stenosis and/or tracheomalacia. Tracheo(s)tomy has been necessary in a few of these children. One patient has been reported with inspiratory stridor secondary to laryngeal stenosis. Joint laxity is progressive and results in dislocations mainly affecting the hips and the knees. The changes in the spine include sacral dysraphism, mild platyspondyly (or other forms of abnormally shaped vertebrae), and decreased interpeduncular distance. Scoliosis may develop, but is usually mild.

Preoperative investigations are determined by the specific disease pattern. Pulmonary function testing, echocardiography, and arterial blood gas analysis should be performed in the presence of kyphoscoliosis and/or the narrowing of the chest. Electrocardiography and echocardiography should also be performed if cardiac dysfunction or congenital cardiac lesions are suspected. A detailed neurological evaluation should be performed in disorders associated with cervical instability and in the presence of kyphoscoliosis because of its association with paraplegia. Facial dysmorphisms may indicate difficult airway management. Cervical spine imaging may be required to ascertain bony stability. Renal function should be checked because of occasional renal dysfunction. Regional anesthesia is not contraindicated per se, but central neuraxial blocks may be difficult to perform given the anomalies of the spine (hyperlordosis, kyphoscoliosis, diminished interpeduncular distance). Some patients may be mentally retarded, hence cooperation may be difficult. Anxiolytic and sedative premedication (careful in patients with cardiopulmonary compromise) and the presence of the primary caregiver for induction may be helpful. Kyphoscoliosis with associated respiratory dysfunction increases the risk for postoperative mechanical ventilation, which should be arranged in advance.

Expect airway management to be difficult. Maintain spontaneous ventilation until the airway has been secured and lung ventilation confirmed. A laryngeal mask airway should be available in case of failure to ventilate and/or intubate. Cervical instability and subluxations require in-line stabilization of the cervical spine during direct laryngoscopy. Primary fiberoptic tracheal intubation may therefore be the approach of choice for these patients. Careful positioning is requested secondary to joint laxity with the risk of dislocations.

Avoid neuromuscular blockers until the airway has been secured.

Morquio Syndrome: An inborn error of metabolism characterized by the deficiency of one of ten specific lysosomal enzymes, resulting in the inability to metabolize complex carbohydrates (mucopolysaccharides) into simpler molecules. May be detected as early as 18 to 24 months of age. The skeletal abnormalities may include macrocephaly, a broad mouth, prominent cheekbones, an unusually small nose, short neck, short barrel chests, disproportionately long arms, enlarged and possibly hyperextensible wrists, stubby hands, and “knock knees.” The joint laxity and bony abnormalities of the spine can result in life-threatening spinal cord compression. The presence of thoracic kyphoscoliosis may also contribute to the risk of spinal cord ischemia during positioning. Aortic regurgitation and deafness have also been reported.