Achondrogenesis: A review with special consideration of achondrogenesis type II (langer‐saldino)

Chen, Harold; Liu, Charlotte T.; Yang, S. Samuel; Opitz, John M.

doi:10.1002/ajmg.1320100411

Cited by 34 publications

(12 citation statements)

References 31 publications

(9 reference statements)

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“…Prognostication and management are based largely on case series suggesting that nearly all affected infants die shortly after birth. [6][7][8][9][10][11][12][13][14][15][16] However, reports of occasional long-term survivors [21][22][23][24] and of decreased mortality with intensive care 25,26 raise questions about the use of the term 'lethal' in this context. Especially, as parents access available knowledge, policies that limit medical treatment are being questioned.…”

Section: Discussionmentioning

confidence: 99%

“…First, we elicited the expert opinion of knowledgeable clinicians (three perinatologists, three neonatologists, one geneticist and two genetics counselors) who reviewed International Classification of Diseases, Ninth Revision codes (ICD-9 codes 740 to 759) 5 and identified the congenital diagnoses they considered lethal. We then performed MEDLINE and Google searches of the diagnoses listed by two-thirds or more of the clinicians, reviewed articles, [6][7][8][9][10][11][12][13][14][15][16] reference texts 17 and websites, 18,19 and retained those diagnoses that were consistently reported to be associated with death before a year of life in nearly all (X85%, when statistics were available) cases. We excluded conjoined twins because of the confounding effect of one infant's condition on the other.…”

Section: Methodsmentioning

confidence: 99%

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Length of life and treatment intensity in infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal

2010

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Objectives: The objectives of this study were (1) to compare age at death and the intensity and cost of medical treatment for infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal.(2) To determine whether greater treatment intensity is associated with longer life.Study Design: This is a retrospective cohort study of all fetuses and neonates with congenital anomalies classified as lethal who were diagnosed or treated at the University of North Carolina Hospitals from January 1998 to December 2003. Result:The cohort consisted of 192 fetuses and infants: 160 were diagnosed prenatally, 2 were diagnosed perinatally, and 30 were diagnosed postnatally. In all, 115 (72%) pregnancies were terminated. Of the liveborn infants, 75% died before 10 days of age and 90% before 4 months of age. Compared with postnatally diagnosed infants, prenatally diagnosed infants received less intense treatment (median average daily Neonatal Therapeutic Intervention Scoring System score 8.3 versus 14.0; P ¼ 0.02), at less cost (median direct cost of hospitalization $1550 versus $8474; P ¼ 0.03) and died sooner (median age at death <1 day versus 4 days; P ¼ 0.01). Greater treatment intensity did not correlate with longer survival (r ¼ À0.04; P ¼ 0.66). Conclusion:Although some kinds of medical therapy may be appropriate for newborns with lethal congenital anomalies, highly aggressive interventions did not prolong survival and should not be offered. Even when pregnancy termination is not elected, infants diagnosed prenatally receive less intense care.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Length of life and treatment intensity in infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal

2010

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“…Secondary cartilages (symphyseal, angular and condylar cartilages) form prenatally and eventually ossify by endochondral ossification during post-natal growth, serving as growth centers (12). The central role of cartilages in mandibular development and growth is exemplified by the mandibular phenotype observed in several chondrodysplasias where mutations in genes involved in chondrocyte function, such as Collagen II (responsible for Achondrogenesis type II), Sox9 (Campomelic dysplasia) or PTHrP (Jansen type of metaphyseal chondrodysplasia) result in abnormal mandibular shape, size or position (14–16). …”

Section: Introductionmentioning

confidence: 99%

Meckel’s and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible

et al. 2016

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Activating FGFR3 mutations in human result in achondroplasia (ACH), the most frequent form of dwarfism, where cartilages are severely disturbed causing long bones, cranial base and vertebrae defects. Because mandibular development and growth rely on cartilages that guide or directly participate to the ossification process, we investigated the impact of FGFR3 mutations on mandibular shape, size and position. By using CT scan imaging of ACH children and by analyzing Fgfr3Y367C/+ mice, a model of ACH, we show that FGFR3 gain-of-function mutations lead to structural anomalies of primary (Meckel’s) and secondary (condylar) cartilages of the mandible, resulting in mandibular hypoplasia and dysmorphogenesis. These defects are likely related to a defective chondrocyte proliferation and differentiation and pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 corrects Meckel’s and condylar cartilages defects ex vivo. Moreover, we show that low dose of NVP-BGJ398 improves in vivo condyle growth and corrects dysmorphologies in Fgfr3Y367C/+ mice, suggesting that postnatal treatment with NVP-BGJ398 mice might offer a new therapeutic strategy to improve mandible anomalies in ACH and others FGFR3-related disorders.

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“…Osteosclerosis with ichthyosis appears to be a different disease [87]. Patients with type II achondrogenesis lack ossification of vertebral, sacral, and pubic bones and have characteristic craniofacial features including prominent forehead, flat face, and micrognathia [88]. Causative de novo mutations are found in the COL2A1 gene [89].…”

Section: Familial Disorders With Pathologic Fractures and Facial Bonementioning

confidence: 98%

Hereditary and Familial Syndromes of Bone and Blood. Genetic Pathways, Diagnostic Pitfalls

Rossbach

2007

Fetal and Pediatric Pathology

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Numerous metabolic disorders, teratogenic agents, and in utero infections lead to congenital bone disease and malformation. This review focuses on hereditary and familial disorders of bone with particular emphasis on impaired hematopoiesis, myelofibrosis, pathologic fractures, and dysmorphology of the forearm and craniofacial structures. The severity of bone disease and marrow dysfunction of any given disorder may vary considerably from one affected individual to the next, and intrapersonal variability over time may be substantial as well. Both can impart difficulty to the appropriate evaluation and delay the correct diagnosis. Many of these disorders are phenotypically quite similar but require very different therapeutic intervention.

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Achondrogenesis: A review with special consideration of achondrogenesis type II (langer‐saldino)

Cited by 34 publications

References 31 publications

Length of life and treatment intensity in infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal

Length of life and treatment intensity in infants diagnosed prenatally or postnatally with congenital anomalies considered to be lethal

Meckel’s and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible

Hereditary and Familial Syndromes of Bone and Blood. Genetic Pathways, Diagnostic Pitfalls

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