Atelosteogenesis I and boomerang dysplasia: a question of nosology

Hunter, Alasdair G. W.; Carpenter, Blair

doi:10.1111/j.1399-0004.1991.tb03060.x

Cited by 33 publications

(4 citation statements)

References 15 publications

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“…The morphology of the cartilage from these patients showed acellular areas within the growth plate and the presence of large multinucleated cells (''giant cells'') ( Fig. 1D) within the resting zone as previously described [Sillence et al, 1982;Yang et al, 1983;Hunter and Carpenter, 1991].…”

Section: Clinical Phenotype Of Aoi and Aoiii Casesmentioning

confidence: 77%

Mutations in two regions ofFLNBresult in atelosteogenesis I and III

Farrington-Rock¹,

Firestein²,

Bicknell³

et al. 2006

Hum. Mutat.

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The filamins are a family of cytoplasmic proteins that bind to and organize actin filaments, link membrane proteins to the cytoskeleton, and provide a scaffold for signaling molecules. Mutations in the gene encoding filamin B (FLNB) cause a spectrum of osteochondrodysplasias, including atelosteogenesis type I (AOI) and atelosteogenesis type III (AOIII). AOI and AOIII are autosomal dominant lethal skeletal dysplasias characterized by overlapping clinical findings that include vertebral abnormalities, disharmonious skeletal maturation, hypoplastic long bones, and joint dislocations. Previous studies have shown that heterozygosity for missense mutations that alter the CH2 domain and repeat 6 region of filamin B produce AOI and AOIII. In this study, 14 novel missense mutations in FLNB were found in 15 unrelated patients with AOI and AOIII. The majority of the mutations resided in exon 2 and exon 3, which encode the CH2 domain of the actin-binding region of filamin B. The remaining mutations were found in exon 28 and exon 29, which encode repeats 14 and 15 of filamin B. These results show that clustering of mutations in two regions of FLNB produce AOI/AOIII, and highlight the important role of this cytoskeletal protein in normal skeletogenesis.

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Section: Clinical Phenotype Of Aoi and Aoiii Casesmentioning

confidence: 77%

Mutations in two regions ofFLNBresult in atelosteogenesis I and III

Farrington-Rock¹,

Firestein²,

Bicknell³

et al. 2006

Hum. Mutat.

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“…In BD and AO1, the short tubular bones have been described as very short, with predominantly the middle phalanges (BD) but in severe cases also the metacarpals and proximal phalanges (AO1) unossified. Postaxial hexadactyly and partial syndactyly of the fingers have also been reported (Farrington‐Rock et al, ; Hunter & Carpenter, ; Sillence et al, ). Again, there is absolutely no ossification of the short tubular bones in POCD fetuses.…”

Section: Discussionmentioning

confidence: 92%

“…The features observed in POCD allow its classification as a distinct entity within the spectrum of giant cell osteochondrodysplasias. BD and AO1 are characterized by nonossification of all parts or of the “distal ends” of the humeri and femora, displaying a missing or seemingly global (BD) or squared and blunt (AO1) structure and associated with attenuated and shortened (in BD, bowed or boomerang like) ulnae, radii, and/or single lower leg bones, and by platyspondyly and abnormal vertebral segmentation (Farrington‐Rock et al, ; Hunter & Carpenter, ; Sillence, Worthington, Dixon, Osborn, & Kozlowski, ). However, absolutely no ossification was found in the long tubular bones and vertebrae, excluding the lateral pedicles, of our POCD fetuses.…”

Section: Discussionmentioning

confidence: 99%

Piepkorn type of osteochondrodysplasia: Defining the severe end of FLNB‐related skeletal disorders in three fetuses and a 106‐year‐old exhibit

Rehder

Laccone

Kircher

et al. 2018

American J of Med Genetics Pt A

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The Piepkorn type of lethal osteochondrodysplasia (POCD) is a rare and lethal dwarfing condition. Four cases have been reported to date. The characteristic features are distinctly shortened "flipper-like" limbs, polysyndactyly, excessive underossification, especially of the limb bones and vertebrae, and large (giant) chondrocytes in the cartilaginous bone primordia. These characteristics allowed the diagnosis of Piepkorn type of osteochondrodysplasia in four new cases, three fetuses of 15 to 22 weeks and one 106-year-old museum exhibit. Piepkorn type of osteochondrodysplasia has been assigned to the giant cell chondrodysplasias such as atelosteogenesis type 1 (AO1) and boomerang dysplasia (BD). Analysis of the Filamin B gene in 3p14.3, which is associated with these disorders, allowed the identification of the first FLNB mutations in Piepkorn type of osteochondrodysplasia. The heterozygous missense mutations, found in the three fetuses, were located in exons 28 and 29, encoding the immunoglobulin-like repeat region R15, one of three mutational hot spots in dominant FLNB-related skeletal disorders. Direct preparations and alcian blue staining revealed single upper and lower arm and leg bone primordia, preaxial oligodactyly, and polysyndactyly with complete fusion and doubling of the middle and end phalanges II-V to produce eight distal finger rays. Considering the unique clinical features and the extent of underossification, Piepkorn type of osteochondrodysplasia can be regarded as a distinct entity within the AO1-BD-POCD continuum.

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“…Review of the literature revealed 8 reports of postmortem examinations in individual cases in which the diagnosis had been confirmed by the demonstration of giant chondrocytes in cartilage [17–24]. Laryngeal stenosis had been identified in each of these cases, and hydronephrosis was also present in 1 instance [17] and the tetralogy of Fallot in another [23].…”

Section: Discussionmentioning

confidence: 99%

Atelosteogenesis Type I: Autopsy Findings

2011

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We have documented the clinical, radiologic, and autopsy findings of 2 fetuses with atelosteogenesis type I, aged 22 and 17 weeks. This rare autosomal dominant lethal skeletal dysplasia is caused by mutation in the FNLB gene. The 17-week-old fetus had some features of atelosteogenesis type II, notably "hitchhiker thumbs," a cleft palate, and midfacial flattening. The histologic demonstration of giant cells in the growth plate cartilage confirmed the diagnosis of atelosteogenesis type I in both fetuses, thereby facilitating accurate prediction of recurrence risks for the parents of the affected fetuses. Autopsy findings included tracheal narrowing and stenosis with pulmonary hypoplasia in both fetuses. Renal microcysts and abnormal branching of the pancreatic duct were also present in 1 of the fetuses, and malrotation of the caecum and retinal dysplasia involving the optic nerve were identified in the other. Postmortem and histologic investigations play an important role in the elucidation of the genetic micromelic skeletal disorders that are lethal in the fetus and neonate.

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Atelosteogenesis I and boomerang dysplasia: a question of nosology

Cited by 33 publications

References 15 publications

Mutations in two regions ofFLNBresult in atelosteogenesis I and III

Mutations in two regions ofFLNBresult in atelosteogenesis I and III

Piepkorn type of osteochondrodysplasia: Defining the severe end of FLNB‐related skeletal disorders in three fetuses and a 106‐year‐old exhibit

Atelosteogenesis Type I: Autopsy Findings

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