Atelosteogenesis type 2

Other Names: AOII; AO2; Neonatal osseous dysplasia 1; De la Chapelle dysplasia; Atelosteogenesis II

Atelosteogenesis type 2 is a severe disorder of cartilage and bone development. Infants born with this condition have very short arms and legs, a narrow chest, and a prominent, rounded abdomen.

The signs and symptoms of atelosteogenesis type 2 are similar to those of another skeletal disorder called diastrophic dysplasia; however, atelosteogenesis type 2 is typically more severe. As a result of serious health problems, infants with this disorder are usually stillborn or die soon after birth from respiratory failure. Some infants, however, have lived for a short time with intensive medical support.

Epidemiology

Atelosteogenesis type 2 is an extremely rare genetic disorder; its incidence is unknown.

Cause

Atelosteogenesis type 2 is one of several skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene disrupt the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of atelosteogenesis type 2.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

The signs and symptoms of atelosteogenesis type 2 include an opening in the roof of the mouth (a cleft palate), characteristic facial features, an inward- and upward-turning foot (clubfoot), and unusually positioned thumbs (hitchhiker thumbs).

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 30%-79% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Bell-shaped thorax
• Bilateral talipes equinovarus(Club foot on both sides)
• Brachydactyly(Short fingers or toes)
• Broad metacarpals(Wide long bones of hand)
• Broad phalanx(Wide digital bones)
• Camptodactyly(Permanent flexion of the finger or toe)
• Dumbbell-shaped femur(Dumbbell-shaped thighbone)
• Equinovarus deformity
• Excessive femoral anteversion
• Genu valgum(Knock knees)
• Hitchhiker thumb
• Laryngeal cartilage malformation
• Laryngeal stenosis
• Metatarsus adductus(Front half of foot turns inward)
• Narrow chest(Low chest circumference)
• Pulmonary hypoplasia(Small lung)
• Rhizomelic arm shortening
• Sandal gap(Gap between 1st and 2nd toes)
• Short femur(Short thighbone)
• Short lower limbs(Short legs)
• Short metacarpal(Shortened long bone of hand)
• Short neck(Decreased length of neck)
• Short phalanx of finger(Short finger bones)
• Short ribs
• Thoracolumbar kyphoscoliosis
• Tibial torsion
• Tracheobronchomalacia
• Ulnar deviation of the hand or of fingers of the hand
• Upper limb undergrowth(Short arms)

Diagnosis

Atelosteogenesis type 2 (AO2) is usually lethal at birth or shortly thereafter because of pulmonary hypoplasia and tracheobronchomalacia. AO2 should be suspected when the following are present.

Clinical features

• Rhizomelic limb shortening with normal-sized skull
• Hitchhiker thumbs
• Small chest
• Protuberant abdomen
• Cleft palate
• Distinctive facial features (midface retrusion, depressed nasal bridge, epicanthus, micrognathia)

Other usual findings are ulnar deviation of the fingers, gap between the first and second toes, and clubfoot.

Radiographic findings

• Normal-sized skull with disproportionately short skeleton
• Platyspondyly, hypodysplastic vertebrae, and cervical kyphosis. Ossification of the upper thoracic vertebrae and coronal clefts of the lumbar and lower thoracic vertebrae may be incomplete.
• Hypoplastic ilia with flat acetabulum. The pubic bones are often unossified.
• Shortened long bones with metaphyseal flaring. The distal humerus is sometimes bifid or V-shaped, sometimes pointed and hypoplastic; the femur is distally rounded; the radius and tibia are typically bowed.
• Characteristic hand findings of sulfate transporter-related dysplasia:
• Hitchhiker thumb with ulnar deviation of the fingers (characteristic of diastrophic dysplasia [DTD])
• Gap between the first and second toe (characteristic of ACG1B [when the phalanges are identifiable on x-ray] and DTD)
• Hypoplasia of the first metacarpal bone (also present in ACG1B and DTD)

Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing or multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype.

Treatment

There is no specific treatment available. Decisions regarding supportive therapy versus palliative treatment depend on the degree of respiratory compromise at birth. For long-term survivors, care should include surgical repair of cleft palate. Utility of surgery for club feet is unclear as this is quite complicated and the results limited. Physiotherapy is useful for retaining range of motion.

NIH genetic and rare disease info

• NIH info on Atelosteogenesis type 2

Atelosteogenesis type 2 is a rare disease.

Atelosteogenesis type 2 Resources
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