Medicine:Bent bone dysplasia syndrome

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Short description: Rare genetic skeletal dysplasia
Bent bone dysplasia syndrome
Other namesBBDS; FGFR2-related bent bone dysplasia; bent bone dysplasia-FGFR2 type
SpecialtyMedical genetics
SymptomsBowed long bones, poor skull mineralization, craniosynostosis, osteopenia, facial differences
Usual onsetPrenatal or neonatal period
CausesPathogenic variants in FGFR2 or LAMA5
Diagnostic methodPrenatal testing
PrognosisOften lethal in the perinatal period; longer-term survival is rare but documented
FrequencyExtremely rare

Bent bone dysplasia syndrome (BBDS) is an extremely rare genetic skeletal dysplasia characterized by bowed long bones and abnormal bone mineralization.[1][2] The most studied form, FGFR2-related bent bone dysplasia, is usually severe and often lethal before or shortly after birth. Reported symptoms include poor mineralization of the skull, craniosynostosis, osteopenia, hypoplastic clavicles and pubic bones, and distinctive craniofacial findings such as low-set ears, hypertelorism, midface hypoplasia, natal teeth, and micrognathia.[3]

Two genetic forms have been described. Bent bone dysplasia syndrome 1 is associated with pathogenic variants in FGFR2, the gene encoding fibroblast growth factor receptor 2.[4][5] Bent bone dysplasia syndrome 2 has been linked to biallelic variants in LAMA5, which encodes laminin subunit alpha 5.[6]

Signs and symptoms

The disorder may be suspected prenatally when imaging shows bowing of the long bones, especially the femora. Other findings can include a poorly mineralized calvarium, craniosynostosis, small or unusually shaped shaped clavicles, abnormal phalanges, hirsutism, hepatic abnormalities and genitourinary abnormalities.[7] The condition is usually described as perinatal lethal, but longer-term survival has been reported in a small number of individuals.[7][8]

Diagnosis

Diagnosis is based on the pattern of clinical and radiographic findings, often followed by molecular genetic testing. Prenatal ultrasound or fetal radiography may show long-bone bowing and other skeletal abnormalities, while postnatal evaluation may include skeletal survey and sequencing of genes associated with skeletal dysplasia.[9]

Prognosis

Most published cases have involved fetal, neonatal, or early infant death. In the largest early clinical series, three longer-term survivors were reported—all of these required ventilatory support.[7] A later case report described survival into early childhood, suggesting that FGFR2-related bent bone dysplasia is not invariably lethal, although severe complications remain common.[10] The oldest documented individual with BBDS is a 4-year-old male (FGFR2 type). Still living as of 2026, he is making developmental progress and is able to walk and interact with others.[10]

See also

References

  1. ↑ "Bent Bone Dysplasia Syndrome". National Organization for Rare Disorders. 2024-07-15. https://rarediseases.org/rare-diseases/bent-bone-dysplasia-syndrome/. 
  2. ↑ Stichelbout, Morgane; Dieux-Coeslier, Anne; Clouqueur, Elodie; Collet, Corinne; Petit, Florence (2015). "A new case of bent bone dysplasia—FGFR2 type and review of the literature". American Journal of Medical Genetics Part A 170 (3): 785–789. doi:10.1002/ajmg.a.37473. PMID 26573129. 
  3. ↑ "Bent bone dysplasia syndrome 1". National Center for Advancing Translational Sciences. https://rarediseases.info.nih.gov/diseases/10965/bent-bone-dysplasia-syndrome-1. 
  4. ↑ Merrill, Amy E.; Sarukhanov, Anna; Krejci, Pavel; Idoni, Brian; Camacho, Nelson; Estrada, Karen D. et al. (2012). "Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling". American Journal of Human Genetics 90 (3): 550–557. doi:10.1016/j.ajhg.2012.02.005. PMID 22387015. 
  5. ↑ Neben, Cynthia L.; Tuzon, Creighton T.; Mao, Xiaojing; Lay, Fides D.; Merrill, Amy E. (2017). "FGFR2 mutations in bent bone dysplasia syndrome activate nucleolar stress and perturb cell fate determination". Human Molecular Genetics 26 (17): 3253–3270. doi:10.1093/hmg/ddx209. 
  6. ↑ Barad, Maya; Csukasi, Flora; Bosakova, Michaela; Martin, Joshua H.; Zhang, Wei; Taylor, Sarah Paige et al. (2020). "Biallelic mutations in LAMA5 disrupts a skeletal noncanonical focal adhesion pathway and produces a distinct bent bone dysplasia". EBioMedicine 62. doi:10.1016/j.ebiom.2020.103075. PMID 33242826. 
  7. ↑ 7.0 7.1 7.2 Krakow, Deborah; Cohn, Daniel H.; Wilcox, William R.; Noh, Grace J.; Raffel, Leslie J.; Sarukhanov, Anna et al. (2016). "Clinical and radiographic delineation of Bent Bone Dysplasia-FGFR2 type or Bent Bone Dysplasia with Distinctive Clavicles and Angel-shaped Phalanges". American Journal of Medical Genetics Part A 170 (10): 2652–2661. doi:10.1002/ajmg.a.37772. PMID 27240702. 
  8. ↑ Malesu, Vijay Kumar (2025-10-23). "Bent Bone Dysplasia: Diagnosis, Prognosis and Management". AZoNetwork. https://www.news-medical.net/health/Bent-Bone-Dysplasia-Diagnosis-Prognosis-and-Management.aspx. 
  9. ↑ Handa, Akihiro; Okajima, Yuko; Izumi, Noriyuki; Yamanaka, Michiko; Kurihara, Yoshimitsu (2016). "Bent bone dysplasia (BBD)-FGFR2 type: the radiologic manifestations in early gestation". Pediatric Radiology 46 (2): 296–299. doi:10.1007/s00247-015-3465-y. PMID 26446305. 
  10. ↑ 10.0 10.1 Bates, Cheyenne; Gill, Pardeep; Choi, Matthew; Mahon, Frances; Yarascavitch, Blake; Lim, Audrey; Ejaz, Resham (2026). "Clinical Presentation of the Longest Reported Living Individual With Bent Bone Dysplasia-FGFR2-Related". American Journal of Medical Genetics Part A 200 (3): 728–732. doi:10.1002/ajmg.a.64295. PMID 41186107. 



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