Filamin B related disorders - Filamin B (FLNB) is a protein suspected to play a role in vertebral segmentation, joint formation and endochondral ossification.

Mutations in FLNB have been reported in five clinically distinct disorders. These disorders are: Larsen syndrome, autosomal dominant (LRS1; MIM 150250), atelosteogenesis, type I (AOI; MIM 108720), atelosteogenesis, type III (AOIII; MIM 108721), boomerang dysplasia (BD; MIM 112310) and spondylocarpotarsal synostosis syndrome (SCT; MIM 272460).

Larsen syndrome, autosomal dominant (LRS1) is a chondrodysplasia characterized by dislocations of various joints and joint laxity, marked hypoplasia of cervical vertebrae with resultant kyphosis and spinal cord compression, a juxtacalcaneal accessory ossification center, flat facies with prominent forehead, hearing loss, depressed nasal bridge and widely spaced eyes, various deformities of the hands and feet, cardiovascular lesions including mitral valve prolapse, aortic dilation and atrial and ventricular septal defects. Adult height is reduced and about 50% display a cleft palate.

Atelosteogenesis, type I (AOI) is a sporadic lethal chondrodysplasia. It is characterized by rhizomelic limb shortening, elbow dislocation, poor ossification of metacarpals and proximal phalanges, short metacarpals and metatarsals, narrow thorax, short neck, cleft palate, midface hypoplasia with frontal bossing, a depressed nasal bridge, micrognathia, vertebral abnormalities and laryngeal stenosis.

Atelosteogenesis, type III (AOIII) is a rare autosomal dominant disorder sharing many features with AOI. Affected patients also have rhizomelic limb shortening, similar facial features, short necks and cervical spine segmentation defects. In addition, they display hitchhiker thumbs with tombstone-shaped proximal phalanges and hitchhiker toes. Characteristic pelvic abnormalities including rounded iliac bones, vertical, block like ischia, flat acetabular roofs with a horizontal sacrum are also reported.

Boomerang dysplasia (BD) is an autosomal dominant, perinatal lethal chondrodysplasia with radiographic and histological findings similar to those of AOI and AOIII. There is a generalized retarded ossification of long bones and vertebral bodies. The radii and fibulae may be absent and remaining long bones are boomerang shaped. The limbs are short, bowed and rigid. Iliac bones can be small.

Spondylocarpotarsal synostosis syndrome (SCT) is a form of short trunk dwarfism with autosomal recessive inheritance. The trunk is disproportionately short and the spine displays abnormal spinal segmentation with block vertebrae, odontoid hypoplasia, subluxation of C2-C3 and unilateral unsegmented bar. The neck is also short. Scoliosis and lordosis are observed. The face is round and broad with a short nose displaying anteverted nares. Patients may have a cleft palate and hearing loss. Carpal and tarsal synostosis with flat feet are features and there is decreased range of motion at the elbows. Restrictive lung disease and renal cysts are reported.