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Table III

Physiopathology, manifestations, diagnosis and management of OI III and trisomy 18 (source author).

  Imperfect Type III osteogenesis (our patient) Trisomy 18
Pathophysiology Molecular level [9] Chromosomal anomaly due to the presence of an additional chromosome 18 (trisomy 18). The trisomy 18 phenotype appears to be related to the presence of three copies of the 18q11–q12 bands [7].
Autosomal dominant mutation in one of the genes encoding α‑1 (chromosome 17) and α‑2 (chromosome 7) type-I collagen chains:
– Quantitative abnormality (light and intermediate OI) or
– Qualitative abnormality (severe and lethal OI).
Tissue level [1,2]
Increased bone remodeling with predominant osteoclast resorption: thinner cortical thickness and fewer and thinner spongy trabeculae.
Clinical manifestations Skeletal manifestations – Intrauterine and postnatal growth retardation,
– Frequent prenatal and postnatal fractures – Increased risk of perinatal or postnatal mortality,
– Deformed and shortened long bones: patients are small in stature – Psychomotor disorders and marked cognitive disorders, developmental delays [7] (language, motor, and social skills [12])
– Soft skull at birth deforming during the first months of life: triangular face, with macrocephaly, micrognathia, small facial mass
– Osteoporotic collapse of vertebrae, resulting in kyphosis and/or scoliosis,  
– Thoracic deformations, severe respiratory insufficiency Major malformations are frequent [7,13]
– Cardiac (>90% cases): interatrial or ventricular septal defects, persistent ductus arteriosus, or valvular pathologies
Dentinogenesis imperfecta was observed in 80% affected patients [9] – Renal: hydronephrosis, unilateral or bilateral renal agenesis
  – Respiratory: central apnea, upper airway obstruction
Other extraskeletal manifestations – Ophthalmic: microphthalmia, coloboma
–Ligament laxity: found at the TMJ level – Labioalveolopalatal clefts are sometimes observed.
 • Joint pain, difficulty in chewing [10]  
 • Developmental anomaly [11] Craniofacial manifestations are typical: face emaciated and hypertrophied, microcephaly, dolichocephaly, microretrognathism, hypertelorism, pointed ears
– Bluish discoloration of sclera [1]  
– Hearing: hearing loss in 58% adults [1] The hands show overlapping fingers, small fingernails, and underdeveloped thumbs. At the trunk level, the sternum appears smaller [7,13]
– Cardiovascular system − coagulation abnormalities with uncommon and benign vascular tissue disorders [1]  
– Renal impairment: hypercalcuria [1]  
– Neurological impairment: headache, cranial nerve impairment, hyperreflexia [1]  
Diagnosis Diagnostic criteria: essentially clinical; lack of consensus May be suspected during pregnancy with ultrasound (growth stunting, malformations, multiple choroid plexus cysts, etc.) and confirmed by the fetal karyotype
– Blue sclera Serum markers (also used to screen for trisomy 21) may be abnormal [7]
– Dentinogenesis imperfecta: mainly found in temporary dentition [9]  
– Family history of the disease [1,2,9]  
In case of suspected impairment: mandatory assessment of bone density [2]  
Prognosis Support Objective: To help the patient acquire optimum motor and functional skills [1,9]  
Interdisciplinary support >95% of affected fetuses die in utero; 50% babies with trisomy 18 live >1 week, 5%–10% live for the first year. The most frequent causes of death are respiratory failure and cardiac arrest as a result of malformations
Possible surgical treatement: possible use of bisphosphonates (BP) (inhibition of bone resorption via inhibition of osteoclasts  
Action: limiting the incidence of fractures).  
– Pamidronate administered intravenously (IV) [2]: reduction of bone pain, improvement of quality of life, rapid increase of the bone mineral mass Prolonged survival (sometimes up to adulthood) is possible, especially in the case of genetic mosaicism or partial trisomy 21 (by translocation) [7]
Decreased risk of fractures [14]  
– Alendronate in bones: decreased number of fractures [2]  
NB: The benefit/risk ratio is to be considered for each patient; regular assessment of patient's oral health is essential to track potential infectious foci and prevent a possible osteoradionecrosis of the maxilla [15] Medical management is limited to supportive care, the surgical treatment of malformations does not change the prognosis significantly [7]

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