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Bent bone dysplasia syndrome 1(BBDS1)

MedGen UID:
482877
Concept ID:
C3281247
Disease or Syndrome
Synonyms: BBDS1; FGFR2-related bent bone dysplasia
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): FGFR2 (10q26.13)
 
Monarch Initiative: MONDO:0013815
OMIM®: 614592
Orphanet: ORPHA313855

Definition

Bent bone dysplasia syndrome-1 (BBDS1) is a perinatal lethal skeletal dysplasia characterized by poor mineralization of the calvarium, craniosynostosis, dysmorphic facial features, prenatal teeth, hypoplastic pubis and clavicles, osteopenia, and bent long bones (Merrill et al., 2012). Genetic Heterogeneity of Bent Bone Dysplasia Syndrome BBDS2 (620076) is caused by mutation in the LAMA5 gene (601033) on chromosome 20q13. [from OMIM]

Clinical features

From HPO
Clitoral hypertrophy
MedGen UID:
57848
Concept ID:
C0156394
Finding
Hypertrophy of the clitoris.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Short clavicles
MedGen UID:
96529
Concept ID:
C0426799
Congenital Abnormality
Reduced length of the clavicles.
Decreased calvarial ossification
MedGen UID:
322270
Concept ID:
C1833762
Finding
Abnormal reduction in ossification of the calvaria (roof of the skull consisting of the frontal bone, parietal bones, temporal bones, and occipital bone).
Coronal craniosynostosis
MedGen UID:
344694
Concept ID:
C1856266
Congenital Abnormality
Premature closure of the coronal suture of skull.
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 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.
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.
Bent long bone
MedGen UID:
1842053
Concept ID:
C5826454
Anatomical Abnormality
A developmental defect of a long bone, such as the femur or the humerus, characterized by a sharply curve deviation located in the diaphysis (shaft) of the bone.
Natal tooth
MedGen UID:
10268
Concept ID:
C0027443
Finding
A tooth present at birth or erupting within the first month of life.
Gingival overgrowth
MedGen UID:
87712
Concept ID:
C0376480
Finding
Hyperplasia of the gingiva (that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
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.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Abnormally large globe
MedGen UID:
344595
Concept ID:
C1855852
Finding
Diffusely large eye (with megalocornea) without glaucoma.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Bent bone dysplasia syndrome 1 in Orphanet.

Recent clinical studies

Etiology

Alanay Y, Krakow D, Rimoin DL, Lachman RS
Am J Med Genet A 2007 Jun 1;143A(11):1159-68. doi: 10.1002/ajmg.a.31711. PMID: 17486589
Cormier-Daire V, Geneviève D, Munnich A, Le Merrer M
Clin Genet 2004 Sep;66(3):169-76. doi: 10.1111/j.0009-9163.2004.00307.x. PMID: 15324311

Diagnosis

Shirodkar D, Smithson SF, Keen R, Lester T, Banos-Pinero B, Burren CP
BMC Med Genomics 2024 Jun 15;17(1):160. doi: 10.1186/s12920-024-01931-6. PMID: 38879467Free PMC Article
Alanay Y, Krakow D, Rimoin DL, Lachman RS
Am J Med Genet A 2007 Jun 1;143A(11):1159-68. doi: 10.1002/ajmg.a.31711. PMID: 17486589
Kozlowski K, Tenconi R
Am J Med Genet 1996 May 3;63(1):17-9. doi: 10.1002/(SICI)1096-8628(19960503)63:1<17::AID-AJMG6>3.0.CO;2-P. PMID: 8723081
Rönning O, Myllarniemi S, Perheentupa J
Cleft Palate J 1978 Jan;15(1):49-55. PMID: 272241

Therapy

Ferrante MI, Romio L, Castro S, Collins JE, Goulding DA, Stemple DL, Woolf AS, Wilson SW
Hum Mol Genet 2009 Jan 15;18(2):289-303. Epub 2008 Oct 29 doi: 10.1093/hmg/ddn356. PMID: 18971206Free PMC Article

Prognosis

Shirodkar D, Smithson SF, Keen R, Lester T, Banos-Pinero B, Burren CP
BMC Med Genomics 2024 Jun 15;17(1):160. doi: 10.1186/s12920-024-01931-6. PMID: 38879467Free PMC Article

Clinical prediction guides

Sergienko NM, Kondratenko YN, Yakimov AK
Eur J Ophthalmol 2009 Jan-Feb;19(1):143-6. doi: 10.1177/112067210901900123. PMID: 19123164
Rönning O, Myllarniemi S, Perheentupa J
Cleft Palate J 1978 Jan;15(1):49-55. PMID: 272241

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