Osteogenesis imperfecta (OI) is a group of rare inherited disorders of connective tissue with the common feature of excessive fragility of bones.[1] It is caused by mutations in the collagen, type I, alpha 1 and collagen type I alpha 2 genes, which encode the alpha 1 and the alpha 2 chain of type I procollagen, respectively.[2] Molecular genetic studies have detected more than 150 mutations of these genes.[2] Other mutations have been identified in the leucine proline-enriched proteoglycan 1, cartilage associated protein and peptidyl-proly lisomerase B genes.[3,4]

The incidence is 1:20,000 and occurs in all races and ethnicity.[5] It is mostly inherited as an autosomal dominant disorder, but autosomal recessive forms have been reported.[6,7] The clinical classification by Sillence et al., is the most helpful in prognosis and genetic counseling and it groups OI into four types: Type I OI is mild, type II is perinatal lethal, type III is progressive deforming and type IV is moderately severe.[8] It is characterized by multiple and recurrent fractures, which are intrauterine or perinatal or post-natal. Other features include blue sclera, otosclerosis with hearing loss, high arched palate, hyperlaxity of ligaments and skin, “dentinogenesis imperfecta” (defective dentition), scoliosis and growth retardation. Wormian bones could also be seen on skull X-ray. Intelligence is not affected.[3]

Diagnosis can be made clinically. Radiographic support and confirmation by collagen analysis of skin fibroblast culture or blood deoxyribonucleic acid analysis may be necessary in some cases.[5,9] This is important for genetic counseling and cases of suspected child abuse. Prenatal diagnosis for at risk pregnancies by fetal ultrasonography in the early 2^nd trimester is possible and enables care.[5,10] There’s no cure for OI.Osteogenesis Imperfecta Bone Essay..  Management is multidisciplinary involving mainly surgery, physiotherapy and rehabilitation. However, medical treatment, especially with bisphosphonate have shown good prospects.[3,5,9]

This case is being reported because of its rarity, especially among blacks and also, to review the literature to highlight the challenges and advances in its management.

Case Report

O.E [Figure 1] was a male neonate delivered to a 33-year-old para 2 female at University of Nigeria Teaching Hospital, Enugu. He was admitted to the new born special care unit (NBSCU) 10 min after birth for inability to cry at birth, multiple deformities with abnormal body posture.

His mother received routine antenatal care and pregnancy was uneventful. Only routine drugs were used during pregnancy. Prenatal ultrasonography detected no fractures or other abnormalities. Onset of labor was spontaneous and lasted about 8 h with spontaneous vertex delivery. Apgar score was four at 10 min. There was no history of the tendency to fractures in the family and no family history of any baby with fracture at birth.

On examination in the NBSCU, he was found to be in “frog like position” with abnormal movement of the left thigh. He was in respiratory distress with acrocyanosis. He had blue-grey sclera and micrognathia with a high arched palate. Musculoskeletal system examination revealed pectus excavatum, fixed flexion deformity of the fingers, crepitus of the right humerus and ulnar and both femurs with bilateral talipes equinovarus and micromelia.

A diagnosis of severe birth asphyxia in a neonate with OI type II was made. Radiograph revealed fractures of the right humerus, ulna and femur with osteopenia. Treatment was mainly supportive with minimal handling, intermittent suctioning and intra-nasal oxygen administration. The parents were counseled and the baby was also reviewed by the orthopaedic surgeons and anesthetist for later surgical intervention when he stabilized. However, he continued to deteriorate until his death on the 7^th day of life. Osteogenesis Imperfecta Bone Essay..

Discussion/Literature Review

OI is a rare disorder. It has variously been called “osteopsathyrosis idiopathica” by Lobstein, “fragilitus osseum”, hereditary fragility of bone, later brittle bone disease and fragile bone disease, but the current name “OI” was coined by Vrolik in 1845.[11,12] The disorder was first brought to the limelight by the Swede, Olof Jakob Ekman in his doctorate thesis at Uppsala in 1788 as “osteomalacia congenital” involving three generations.[12,13] Since then, various researchers have tried to describe and classify this disorder into various types: In 1906, Looser, proposed the classification: “Congenita” and “tarda” based on time of fractures.[14] Congenita type has fracture in-utero and most were either still birth or died soon after. OI congenita was found in children whose parents have no traces of the disease while OI tarda was the hereditary form. In 1975, Bauze et al.,[15] describing the clinical, radiological and biochemical features of 42 patients classified OI into three: mild, moderate and severe based on deformity of one or more of the long bones. Mild had no long bone deformity; moderate had minor long bone deformities while severe had severe long bone deformities. One of their arguments is that long bone deformity is a strong prognostic feature and easily recognizable.

The most widely acceptable classification was by Sillence et al.,[8] in 1979, in which they grouped the disorder into four: Type I; dominantly inherited OI with blue sclera, type II; perinatally lethally deforming OI with crumpled femora, type III; progressively deforming OI with normal sclera and type IV; dominantly inherited OI with normal sclerae. Type I is a mild form with recurrent fractures and blue sclera. It has A and B subtypes depending on the absence or presence of dentinogenesis imperfecta. Fractures are less common after puberty. Osteogenesis Imperfecta Bone Essay.. Type II is autosomal recessive and generally lethal in the newborn period with multiple congenital fractures, micromelia and severe lung disease. Types III and IV represent intermediate phenotypes with type III being the most severe non-lethal form causing significant bony deformity secondary to multiple fractures, which can be congenital. Type IV also has subtypes A and B based on the presence of dentinogenesis imperfecta.

Over the past few decades, five additional types (V-IX) have been identified using histological and molecular findings.[6,7] Plotkin[16] proposed a classification of OI as syndromes secondary to mutations in type I pro-collagen genes and “syndromes resembling osteogenesis imperfecta” as those secondary to mutations other than the type I pro-collagen genes.

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The diagnosis of OI type II in our patient was based on the clinical features of multiple fractures at birth, blue-grey sclera, micromelia and radiological evidence of osteopenia. Although, there was no positive family history suggestive of OI or other skeletal malformations, it was noted that sporadic cases were most likely in type II.[8] Akiode et al., in Sagamu,[17] and Akinola et al., in Lagos,[18] both in Western Nigeria reported a single and two cases respectively of female babies based on the clinical findings of multiple fractures, blue sclera and craniotabes at birth with radiological evidence of defective ossification of the skull. Osteogenesis Imperfecta Bone Essay..

Although, reports available,[5,19] show no racial or ethnic variation, the sparseness of reports from Africa and obvious absence of blacks in most of the case reports from other continents may be an indication of low incidence in Africans. It may also be as a result of under reporting due to wide unavailability of facilities for disease confirmation. Although, an autosomal recessive form of type III, which is very rare, has been reported as been relatively more common among South African black population,[20] the etiology is not certain as type I collagen structural genes Colia one and two have not been demonstrated to be mutated in the affected population.[21] There have also been reports of OI in twins from Burundi[22] and more recently Nigeria.[23]

Prenatal diagnosis by fetal ultrasonography is possible,[5] but no abnormality was detected in our patient prenatally. Likewise, in the first case earlier reported within the country. The other case, report did not state the ultrasonography findings. It’s also possible that the fractures occurred during delivery in both cases since prenatal diagnosis is mainly based on the presence of fractures. Fractures can occur even on minimal stress, but there is no empiric data to prove that caesarean section will improve outcome over vaginal birth even when diagnosed prenatally.[24] However, its poor prognostic course raises an ethical question of termination of pregnancy on detection. Despite this, advances in technology continue to proffer options for these children.  Osteogenesis Imperfecta Bone Essay.