Atelosteogenesis type I

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[edit | edit source]

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[edit | edit source]

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).

Pathogenesis[edit | edit source]

Filamin B forms part of the actin cytoskeleton. How these mutations produce the clinical picture is not yet clear.

Diagnosis[edit | edit source]

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[edit | edit source]

This includes^[9]

Treatment[edit | edit source]

There is currently no curative treatment for this condition.

Supportive management is all that is currently available.

Epidemiology[edit | edit source]

This is a rare condition with a prevalence of < 1/10⁶. The total number of cases reported to date is <20.

History[edit | edit source]

This condition was first described by Maroteaux et al. in 1982.^[10]

References[edit | edit source]

↑ 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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[Sillence1997-1] 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

[Temple1990-2] Temple K, Hall C A, Chitty L, Baraitser M (1990) A case of atelosteogenesis. J Med Genet 27: 194-197

[Wessels2011-3] Wessels A, Wainwright HC, Beighton P (2011) Atelosteogenesis type I: autopsy findings. Pediatr Dev Pathol 14(6):496-500

[Farrington-Rock2006-4] 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

[Li2013-5] 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

[Jeon2014-6] 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

[Stevenson1983-7] Stevenson RE, Wilkes G (1983) Atelosteogenesis with survival beyond the neonatal period. Proc. Greenwood Genet Center 2: 32-38

[Ueno2002-8] 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

[Nishimura1997-9] 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

[Maroteaux1082-10] 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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