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Fibrochondrogenesis 2(FBCG2)

MedGen UID:
482758
Concept ID:
C3281128
Disease or Syndrome
Synonym: FBCG2
 
Gene (location): COL11A2 (6p21.32)
 
Monarch Initiative: MONDO:0013795
OMIM®: 614524

Definition

Fibrochondrogenesis is a severe skeletal dysplasia characterized by a flat midface, short long bones, short ribs with broad metaphyses, and vertebral bodies that show distinctive hypoplastic posterior ends and rounded anterior ends, giving the vertebral bodies a pinched appearance on lateral radiographic views. The chest is small, causing perinatal respiratory problems which usually, but not always, result in lethality. Affected individuals who survive the neonatal period have high myopia, mild to moderate hearing loss, and severe skeletal dysplasia (summary by Tompson et al., 2012). For a discussion of genetic heterogeneity of fibrochondrogenesis, see FBCG1 (228520). [from OMIM]

Additional description

From MedlinePlus Genetics
People with fibrochondrogenesis also have distinctive facial features. These include prominent eyes, low-set ears, a small mouth with a long upper lip, and a small chin (micrognathia). Affected individuals have a relatively flat-appearing midface, particularly a small nose with a flat nasal bridge and nostrils that open to the front rather than downward (anteverted nares). Vision problems, including severe nearsightedness (high myopia) and clouding of the lens of the eye (cataract), are common in those who survive infancy. Most affected individuals also have sensorineural hearing loss, which is caused by abnormalities of the inner ear.

Fibrochondrogenesis is a very severe disorder of bone growth. Affected infants have a very narrow chest, which prevents the lungs from developing normally. Most infants with this condition are stillborn or die shortly after birth from respiratory failure. However, some affected individuals have lived into childhood.

Fibrochondrogenesis is characterized by short stature (dwarfism) and other skeletal abnormalities. Affected individuals have shortened long bones in the arms and legs that are unusually wide at the ends (described as dumbbell-shaped). People with this condition also have a narrow chest with short, wide ribs and a round and prominent abdomen. The bones of the spine (vertebrae) are flattened (platyspondyly) and have a characteristic pinched or pear shape that is noticeable on x-rays. Other skeletal abnormalities associated with fibrochondrogenesis include abnormal curvature of the spine and underdeveloped hip (pelvic) bones.  https://medlineplus.gov/genetics/condition/fibrochondrogenesis

Clinical features

From HPO
Protuberant abdomen
MedGen UID:
340750
Concept ID:
C1854928
Finding
A thrusting or bulging out of the abdomen.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Metaphyseal cupping
MedGen UID:
323062
Concept ID:
C1837082
Finding
Metaphyseal cupping refers to an inward bulging of the metaphyseal profile giving the metaphysis a cup-like appearance.
Thoracic hypoplasia
MedGen UID:
373339
Concept ID:
C1837482
Congenital Abnormality
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Hypoplastic ischia
MedGen UID:
347146
Concept ID:
C1859447
Finding
Underdevelopment of the ischium, which forms the lower and back part of the hip bone.
Hypoplastic ilia
MedGen UID:
348814
Concept ID:
C1861218
Finding
Underdevelopment of the ilium.
Hypoplastic pubic bone
MedGen UID:
355894
Concept ID:
C1865030
Finding
Underdevelopment of the pubis, which together with the ilium and the ischium, is one of the three bones that make up the hip bone.
Cupped ribs
MedGen UID:
351284
Concept ID:
C1865039
Finding
Wide, concave rib end.
Bell-shaped thorax
MedGen UID:
351320
Concept ID:
C1865186
Finding
The rib cage has the shape of a wide mouthed bell. That is, the superior portion of the rib cage is constricted, followed by a convex region, and the inferior portion of the rib cage expands again to have a large diameter.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.

Recent clinical studies

Etiology

Cheng P, Han P, Zhao C, Zhang S, Wu H, Ni J, Hou P, Zhang Y, Liu J, Xu H, Liu S, Zhang X, Zheng Y, Chai Y
Biomaterials 2016 Mar;81:14-26. Epub 2015 Dec 15 doi: 10.1016/j.biomaterials.2015.12.005. PMID: 26713681
Hall CM, Elçioglu NH
Pediatr Radiol 2004 Jan;34(1):66-74. Epub 2003 Oct 18 doi: 10.1007/s00247-003-1063-x. PMID: 14566438
Al-Gazali LI, Bakir M, Hamid Z, Varady E, Varghes M, Haas D, Bener A, Padmanabhan R, Abdulrrazzaq YM, Dawadu A
Birth Defects Res A Clin Mol Teratol 2003 Feb;67(2):125-32. doi: 10.1002/bdra.10009. PMID: 12769508

Diagnosis

Nixon T, Richards AJ, Lomas A, Abbs S, Vasudevan P, McNinch A, Alexander P, Snead MP
Mol Genet Genomic Med 2020 Sep;8(9):e1354. Epub 2020 Jun 24 doi: 10.1002/mgg3.1354. PMID: 32578940Free PMC Article
Tompson SW, Faqeih EA, Ala-Kokko L, Hecht JT, Miki R, Funari T, Funari VA, Nevarez L, Krakow D, Cohn DH
Am J Med Genet A 2012 Feb;158A(2):309-14. Epub 2012 Jan 13 doi: 10.1002/ajmg.a.34406. PMID: 22246659Free PMC Article
Akawi NA, Al-Gazali L, Ali BR
Clin Genet 2012 Aug;82(2):147-56. Epub 2011 Jul 18 doi: 10.1111/j.1399-0004.2011.01734.x. PMID: 21668896
Chen CP
Taiwan J Obstet Gynecol 2007 Jun;46(2):111-20. doi: 10.1016/S1028-4559(07)60004-7. PMID: 17638618
Hall CM, Elçioglu NH
Pediatr Radiol 2004 Jan;34(1):66-74. Epub 2003 Oct 18 doi: 10.1007/s00247-003-1063-x. PMID: 14566438

Prognosis

Tompson SW, Faqeih EA, Ala-Kokko L, Hecht JT, Miki R, Funari T, Funari VA, Nevarez L, Krakow D, Cohn DH
Am J Med Genet A 2012 Feb;158A(2):309-14. Epub 2012 Jan 13 doi: 10.1002/ajmg.a.34406. PMID: 22246659Free PMC Article
Akawi NA, Al-Gazali L, Ali BR
Clin Genet 2012 Aug;82(2):147-56. Epub 2011 Jul 18 doi: 10.1111/j.1399-0004.2011.01734.x. PMID: 21668896

Clinical prediction guides

Cheng P, Han P, Zhao C, Zhang S, Wu H, Ni J, Hou P, Zhang Y, Liu J, Xu H, Liu S, Zhang X, Zheng Y, Chai Y
Biomaterials 2016 Mar;81:14-26. Epub 2015 Dec 15 doi: 10.1016/j.biomaterials.2015.12.005. PMID: 26713681
Vijzelaar R, Waller S, Errami A, Donaldson A, Lourenco T, Rodrigues M, McConnell V, Fincham G, Snead M, Richards A
BMC Med Genet 2013 Apr 26;14:48. doi: 10.1186/1471-2350-14-48. PMID: 23621912Free PMC Article
Tompson SW, Faqeih EA, Ala-Kokko L, Hecht JT, Miki R, Funari T, Funari VA, Nevarez L, Krakow D, Cohn DH
Am J Med Genet A 2012 Feb;158A(2):309-14. Epub 2012 Jan 13 doi: 10.1002/ajmg.a.34406. PMID: 22246659Free PMC Article
Akawi NA, Al-Gazali L, Ali BR
Clin Genet 2012 Aug;82(2):147-56. Epub 2011 Jul 18 doi: 10.1111/j.1399-0004.2011.01734.x. PMID: 21668896
Al-Gazali LI, Bakir M, Hamid Z, Varady E, Varghes M, Haas D, Bener A, Padmanabhan R, Abdulrrazzaq YM, Dawadu A
Birth Defects Res A Clin Mol Teratol 2003 Feb;67(2):125-32. doi: 10.1002/bdra.10009. PMID: 12769508

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