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Bent bone dysplasia syndrome 2(BBDS2)

MedGen UID:
1824006
Concept ID:
C5774233
Disease or Syndrome
Synonym: BBDS2
 
Gene (location): LAMA5 (20q13.33)
 
Monarch Initiative: MONDO:0859573
OMIM®: 620076

Definition

Bent bone dysplasia syndrome-2 (BBDS2) is characterized by defects in both the axial and appendicular skeleton, with radiographic findings of undermineralized bone and a distinct angulation of the mid femoral shaft. Extraskeletal features include facial dysmorphisms, abnormally formed ears with tags, widely spaced nipples, and atrial septal defects. Abnormalities of muscle function are suggested by the presence of elbow fusions, ulnar flexion contractions at the wrist, and bilateral talipes equinovarus, as well as failure to mount a respiratory effort at birth (Barad et al., 2020). For a general phenotypic description and discussion of genetic heterogeneity of bent bone dysplasia syndrome, see BBDS1 (614592). [from OMIM]

Clinical features

From HPO
Shawl scrotum
MedGen UID:
388088
Concept ID:
C1858539
Congenital Abnormality
Superior margin of the scrotum superior to the base of the penis.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Ulnar deviation of the hand
MedGen UID:
66031
Concept ID:
C0241521
Finding
Divergence of the longitudinal axis of the hand at the wrist in a posterior (ulnar) direction (i.e., towards the little finger).
Short lower limbs
MedGen UID:
98100
Concept ID:
C0426901
Finding
Shortening of the legs related to developmental hypoplasia of the bones of the leg.
Hypoplastic acetabulae
MedGen UID:
375890
Concept ID:
C1846442
Finding
Underdeveloped acetabulae.
Short 1st metacarpal
MedGen UID:
376561
Concept ID:
C1849311
Finding
A developmental defect characterized by reduced length of the first metacarpal (long bone) of the hand.
Short tibia
MedGen UID:
338005
Concept ID:
C1850259
Finding
Underdevelopment (reduced size) of the tibia.
Bowed humerus
MedGen UID:
395269
Concept ID:
C1859460
Finding
A bending or abnormal curvature of the humerus.
Ulnar bowing
MedGen UID:
356099
Concept ID:
C1865847
Finding
Bending of the diaphysis (shaft) of the ulna.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Thin ribs
MedGen UID:
98095
Concept ID:
C0426818
Finding
Ribs with a reduced diameter.
Short sternum
MedGen UID:
108394
Concept ID:
C0575497
Finding
Decreased inferosuperior length of the sternum.
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 cleft vertebrae
MedGen UID:
320483
Concept ID:
C1834954
Finding
Frontal schisis (cleft or cleavage) of vertebral bodies.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Relative macrocephaly
MedGen UID:
338607
Concept ID:
C1849075
Congenital Abnormality
A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Hypoplastic iliac wing
MedGen UID:
351279
Concept ID:
C1865027
Anatomical Abnormality
Underdevelopment of the ilium ala.
Butterfly vertebrae
MedGen UID:
1744309
Concept ID:
C5438458
Congenital Abnormality
A butterfly vertebra (sagittal cleft vertebra or anterior rachischisis) is a sagittal defect in the vertebral body caused by failure of fusion of the two lateral chondrification centers during embryogenesis. The name is based on the appearance of the two hemivertebrae emerging as butterfly wings from the central cleft on x-ray.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Cystic hygroma
MedGen UID:
60195
Concept ID:
C0206620
Neoplastic Process
A cystic lymphatic lesion of the neck.
Webbed neck
MedGen UID:
113154
Concept ID:
C0221217
Congenital Abnormality
Pterygium colli is a congenital skin fold that runs along the sides of the neck down to the shoulders. It involves an ectopic fibrotic facial band superficial to the trapezius muscle. Excess hair-bearing skin is also present and extends down the cervical region well beyond the normal hairline.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Thickened nuchal skin fold
MedGen UID:
324644
Concept ID:
C1836940
Finding
A thickening of the skin thickness in the posterior aspect of the fetal neck. A nuchal fold (NF) measurement is obtained in a transverse section of the fetal head at the level of the cavum septum pellucidum and thalami, angled posteriorly to include the cerebellum. The measurement is taken from the outer edge of the occiput bone to the outer skin limit directly in the midline. An NF measurement greater than 5 mm at 14 to 17+6 weeks of gestation, or 6 mm at 18 to 28 weeks has been associated with a markedly increased risk for Down syndrome.
Wide intermamillary distance
MedGen UID:
473489
Concept ID:
C1827524
Finding
A larger than usual distance between the left and right nipple.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Recent clinical studies

Etiology

Leal GF, Nishimura G, Voss U, Bertola DR, Åström E, Svensson J, Yamamoto GL, Hammarsjö A, Horemuzova E, Papadiogannakis N, Iwarsson E, Grigelioniene G, Tham E
J Bone Miner Res 2018 Apr;33(4):753-760. Epub 2018 Jan 4 doi: 10.1002/jbmr.3348. PMID: 29178448

Diagnosis

Leal GF, Nishimura G, Voss U, Bertola DR, Åström E, Svensson J, Yamamoto GL, Hammarsjö A, Horemuzova E, Papadiogannakis N, Iwarsson E, Grigelioniene G, Tham E
J Bone Miner Res 2018 Apr;33(4):753-760. Epub 2018 Jan 4 doi: 10.1002/jbmr.3348. PMID: 29178448
Stichelbout M, Dieux-Coeslier A, Clouqueur E, Collet C, Petit F
Am J Med Genet A 2016 Mar;170(3):785-9. Epub 2015 Nov 17 doi: 10.1002/ajmg.a.37473. PMID: 26573129
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

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

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