Brittle bone disease: a case report

Brittle bone disease: a case report

Osteogenesis imperfecta (OI) is a rare genetic disorder. Due to considerable phenotypic variability, a classification for OI subtypes was developed based on clinical features and disease severity.

A seven day old female was born at 40+1 weeks gestation whose mother received routine prenatal care and had an uneventful pregnancy. At delivery, the newborn sustained bilateral clavicle fractures. One week later, she attended an unscheduled appointment at the family health unit due to inconsolable crying and pain during the mobilization of the lower left limb of three days’ evolution, which was reported by her parents. On examination, she presented edema in the right coxofemoral joint, asymmetry in the folds, and inconsolable crying during mobilization of both hip joints. She was sent to the emergency department, where a pelvic X-ray was performed which revealed a bilateral fracture of the femur. During hospitalization, a genetic study revealed pathogenic variants of the WNT1 gene, which causes OI type XV.

When a newborn presents fractures, the main differential diagnosis is physical abuse. However, this was ruled out as we knew his mother and family, leaving no other possible evidence of abuse. OI was a highly probable diagnostic hypothesis due to the presence of two other cases of this type of OI in the same region of origin, despite the fact that their parents were not consanguineous and there was no history of fractures in their families.

Although OI is a rare condition, the diagnosis was immediately suspected because there were two confirmed cases of this type in the same geographic area as our patient. In addition, he had bilateral clavicle fractures at birth with no obvious signs or risk factors for abuse. As family physicians, our goal is to support this family throughout their journey and provide the child with the best possible care.

Introduction

Osteogenesis imperfecta (OI) or brittle bone disease is a rare genetic disorder that occurs in 1 in 15,000 to 20,000 births and is characterized by brittle bones and osteopenia [1]. Due to considerable phenotypic variability, a classification of OI types based on clinical features and disease severity was developed. Most forms of OI are autosomal dominant with mutations in one of two genes encoding type I collagen alpha chains, namely COL1A1 (120150) and COL1A2 (120160) [2]. Type XV OI is described as an autosomal recessive form of the disorder characterized by early onset of recurrent fractures, bone deformity, significant reduction in bone density, short stature, and, in some patients, blue sclera. Tooth development and hearing remain normal. Delays in learning and development and brain abnormalities have been observed in some patients. [3,4].

case presentation

A seven-day-old female was born at 40+1 weeks’ gestation whose mother received routine antenatal care along with an uneventful pregnancy. Prenatal ultrasound did not detect fractures or other abnormalities. The baby was born in eutocic delivery without complications, with an Apgar score of 9/10 and the following anthropometric data: weight 3630 g, length 47.50 cm and head circumference 32 cm. At birth she had a bilateral clavicle fracture (Figure 1) with left brachial paresis. One week after the baby was born, she attended an unscheduled consultation at the family health unit due to inconsolable crying and pain during movement of the left lower limb for three days, which was perceived by her mother. On observation, there was edema in the right hip joint, skinfold asymmetry, and inconsolable crying during mobilization of both hip joints. She was sent to the emergency room, where a pelvic X-ray was performed, which revealed a bilateral femur diaphyseal fracture (Figure two), requiring hospitalization with the use of plaster for six weeks. During hospitalization, a genetic study for OI (next generation sequencing panel based on whole exome sequencing of 26 genes, including copy number variation analysis) was performed which revealed the probable pathogenic variant c.324 dup p .(Gly109Argfs*46) in probable homozygosis in the WNT1 gene. This variant is not described in the literature or in the ClinVar database and is present in the gnomAD population database (only one heterozygous individual was reported). pathogenic variants in the WNT1 the gene causes, among other pathologies, type XV OI, with autosomal recessive inheritance. Thus, this result confirms a genetic aetiology for the clinical picture presented. A genetic study of the parents was recommended and performed to confirm homozygosity and establish their carrier status. Currently, we are awaiting the results.

Discussion

OI is known to be a collagen-related disorder caused by defects in collagen structure as well as in genes that affect collagen folding, post-translational processing and modification, bone mineralization, and osteoblast differentiation. [5].

OI type XV is the result of homozygous mutations in WNT1. heterozygous mutations in WNT1 cause predominantly hereditary osteoporosis of early onset, being the genetic test of the parents essential to diagnose and treat this condition as soon as possible [5].

Although clavicle fractures can occur in newborn babies, bilateral clavicle fractures are extremely rare. [6]. Because the infant was neither macrosomic nor postterm and did not have an instrumental delivery, the bilateral clavicle fracture was not expected. When a newborn presents fractures, the main differential diagnosis is physical abuse or fall [7]. This was ruled out after confirming it with the mother and other relatives. In addition, there was no other evidence of abuse, such as skin injuries, and the fractures did not show any specific patterns. OI was a highly probable diagnostic hypothesis due to the existence of two other cases of OI in the same region of origin, although his parents were not consanguineous and there was no history of similar fractures in the families of both parents. Considering the potential brain abnormalities, learning, and/or developmental delay associated with OI XV, these patients should be followed by a multidisciplinary team and early involvement and family support should be encouraged. [8,9].

Conclusions

Although OI is a rare condition, the diagnosis was suspected immediately after evaluation at the family health unit because there were two confirmed cases of a similar condition in the same geographic area as our patient. In addition, he had bilateral clavicle fractures at birth with no obvious signs or risk factors for abuse. The suspicion of abuse should always be the first thing to rule out in newborns with multiple fractures. The diagnosis can only be verified by relevant genetic testing and although there is no apparent relationship between the other cases, there could be a role of shared family history in the past. As family doctors, we are obliged to accompany this family throughout its journey, providing the best possible care for the child.

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