Medicine:Atelosteogenesis type I
| Atelosteogenesis type I | |
|---|---|
| Other names | Spondylo-humero-femoral dysplasia |
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| Autosomal dominant pattern is the inheritance manner of this condition | |
| Specialty | Medical genetics |
Atelosteogenesis type I is a rare autosomal dominant condition.[1] This condition is evident at birth and is associated with a very poor prognosis for the baby. It may be diagnosed antenatally.
Signs and symptoms
Clinical features include[2]
- Abnormal facies
- Prominent forehead
- Hypertelorism
- Depressed nasal bridge with a grooved tip
- Micrognathia
- Cleft palate
- Severe short limbed dwarfism
- Joint dislocations (hip, knee and elbow joints)
- Club feet
- Cardiorespiratory failure
Cardiorespiratory failure is due to pulmonary hypoplasia or tracheobronchial hypoplasia.[3]
Genetics
This condition is caused by mutations in the filamin B (FLNB) gene.[4][5][6] This gene is located on the short arm of chromosome 3 (3p14).[citation needed]
Pathogenesis
Filamin B forms part of the actin cytoskeleton. How these mutations produce the clinical picture is not yet clear.[citation needed]
Diagnosis
This condition is evident at birth and may be diagnosed antenatally with ultrasound or magnetic resonance imaging. The infants may be still born. Those that are live born do not survive long.[7]
Radiological findings include[8]
- Severe platyspondyly
- Distally tapered, shortened, incomplete or absent humeri and femurs
- Shortened or bowed radii, ulnas and tibias
- Hypoplastic pelvis and fibulas
- Deficient ossification of the metacarpals, middle and proximal phalanges
Differential diagnosis
This includes[9]
- Achondroplasia
- Achondrogenesis
- Atelosteogenesis III
- Boomerang dysplasia
- Campomelic dysplasia
- Ellis–Van Creveld syndrome
- Hypophosphatasia
- Melnick Needles syndrome
- Metatropic dysplasia
- Osteogenesis imperfecta
- Roberts syndrome
- Short-rib polydactyly syndrome
- Thanatophoric dysplasia
Treatment
There is currently no curative treatment for this condition. Supportive management is all that is currently available.[citation needed]
Epidemiology
This is a rare condition with a prevalence of less than 1/106. The total number of cases reported to date is less than 20.
History
This condition was first described by Maroteaux et al. in 1982.[10]
References
- ↑ Sillence D, Worthington S, Dixon J, Osborn R, Kozlowski K (1997) Atelosteogenesis syndromes: a review, with comments on their pathogenesis. Pediatr Radiol 27(5):388-396
- ↑ Temple K, Hall C A, Chitty L, Baraitser M (1990) A case of atelosteogenesis. J Med Genet 27: 194-197
- ↑ Wessels A, Wainwright HC, Beighton P (2011) Atelosteogenesis type I: autopsy findings. Pediatr Dev Pathol 14(6):496-500
- ↑ Farrington-Rock C, Firestein MH, Bicknell LS, Superti-Furga A, Bacino CA, Cormier-Daire V, Le Merrer M, Baumann C, Roume J, Rump P, Verheij JB, Sweeney E, Rimoin DL, Lachman RS, Robertson SP, Cohn DH, Krakow D (2006) Mutations in two regions of FLNB result in atelosteogenesis I and III. Hum Mutat 27(7):705-710
- ↑ Li BC, Hogue J, Eilers M, Mehrotra P, Hyland J, Holm T, Prosen T, Slavotinek AM (2013) Clinical report: Two patients with atelosteogenesis type I caused by missense mutations affecting the same FLNB residue. Am J Med Genet A 161A(3):619-625. doi: 10.1002/ajmg.a.35792
- ↑ Jeon GW, Lee MN, Jung JM, Hong SY, Kim YN, Sin JB, Ki CS (2014) Identification of a de novo heterozygous missense FLNB mutation in lethal atelosteogenesis type I by exome sequencing. Ann Lab Med 34(2):134-138. doi: 10.3343/alm.2014.34.2.134
- ↑ Stevenson RE, Wilkes G (1983) Atelosteogenesis with survival beyond the neonatal period. Proc. Greenwood Genet Center 2: 32-38
- ↑ Ueno K, Tanaka M, Miyakoshi K, Zhao C, Shinmoto H, Nishimura G, Yoshimura Y (2002) Prenatal diagnosis of atelosteogenesis type I at 21 weeks' gestation. Prenat Diagn 22(12):1071-1075
- ↑ Nishimura G, Horiuchi T, Kim OH, Sasamoto Y (1997) Atypical skeletal changes in otopalatodigital syndrome type II: phenotypic overlap among otopalatodigital syndrome type II, boomerang dysplasia, atelosteogenesis type I and type III, and lethal male phenotype of Melnick-Needles syndrome. Am J Med Genet 73(2):132-138
- ↑ Maroteaux P, Spranger J, Stanescu V, Le Marec B, Pfeiffer RA, Beighton P, Mattei JF (1982) Atelosteogenesis. Am J Med Genet 13: 15-25
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