What Is Bent Bone Dysplasia Syndrome?
Bent bone dysplasia syndrome is a rare genetic disorder of autosomal dominant inheritance and is characterized by various skeletal anomalies. It is a deadly disorder characterized by poor mineralization of the top part of the skull bone, abnormal premature fusion of the bones of the baby’s skull (craniosynostosis), underdevelopment of the pubic bone (hypoplastic pubis), underdeveloped collarbone (clavicle), deformities or abnormalities in the facial features, low bone mineral density, long bent bones, and prenatal teeth. This condition is often associated with altered or abnormalities in the FGFR2 gene (fibroblast growth factor receptor 2).
What Is the FGFR2 Gene?
The FGFR2 gene in humans produces a protein called Fibroblast growth factor receptor 2 (FGFR2). Fibroblast growth factor receptor 2 is the biological transducer for fibroblast growth factor. FGFR2 is a class of proteins that are involved in essential processes such as cell growth, cell division, cell differentiation, wound healing, bone development, and during embryonic development. This gene is found in chromosome 10. They play a vital role in bone development during embryogenesis. Any alterations or genetic changes (mutations) in this gene affect normal bone development. Patients affected with bent bone dysplasia have been shown to have a mutated FGFR2 gene.
How Is Bent Bone Dysplasia Syndrome Inherited?
Genetic disease occurs when there are harmful changes to the individual’s DNA (deoxyribonucleic acid) material. It may either be inherited from the affected parents or random genetic changes due to an underlying reason. Bent bone dysplasia is inherited in an autosomal dominant pattern, which means that a single copy of the altered or mutated gene is enough to cause the disease. Normally for a genetic disorder, two mutated genes are received from each of the parents. In the dominant inheritance pattern, only one copy of the abnormal gene can cause the disease. Autosomal refers to the presence of the altered gene found on any of the 22 numbered pairs of non-sex chromosomes other than the X and Y chromosome (sex chromosome). The chances of passing down an abnormal gene from the affected parents are 50 percent in each pregnancy, regardless of the sex of the patient.
What Are the Predisposing Factors?
Not every individual with predisposing factors is affected by the condition. The presence of predisposing factors increases the chances of getting the condition. The highest risk factor predisposing the bent bone dysplasia syndrome is the presence of a familial history of the condition. The presence of pathogenic variants in the parents increases the chances of inheriting the genetic condition in their offspring.
What Are the Signs and Symptoms?
The signs and symptoms of bent bone dysplasia begin to occur during pregnancy and in newborns four weeks of age. Bent bone dysplasia has diverse clinical features affecting various parts of the skeletal system. Symptoms may differ for each person. The common symptoms of this condition are:
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Abnormalities in the position of the external ear.
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Presence of a low set of ears.
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Abnormal Shape of the Thorax: The newborns affected with this condition have a ribcage in the shape of a wide-mouthed bell. Ribcage has a constricted upper portion and the lower portion is expanded with increased diameter.
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Newborns with this condition might have disproportionate toes and fingers. The toes and fingers are shorter than normal.
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Presence of deformity in the morphology of the clitoris. Changes in the size of the clitoris.
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Stationary Night Blindness: This is a congenital condition affecting the retina which is a specialized tissue in detecting light and colors.
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Coronal Craniosynostosis: The word synostosis refers to the abnormal fusion of the bones. Newborns with this condition have a premature closure of the sutures present at the top part of the skull. It may result in a flattened forehead.
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Abnormal reduction in the normal process of bone formation (ossification) in the skull bone.
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Extramedullary Hematopoiesis: The process of hematopoiesis refers to the formation of blood cells. In this condition, there is an activation and formation of blood cells outside the bone marrow.
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Abnormal increase in hair growth.
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Hypertelorism (an abnormal increase in distance between the orbits).
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Under-development of the pubic bone.
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Undeveloped mandible during birth.
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Midface retrusion.
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Presence of teeth during birth.
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Presence of low bone mineral density.
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Lower limb deformities.
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Abnormal bow-shaped curvature of the long bones of the leg.
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Rarely there is an enlargement of the spleen and the liver.
How Is It Diagnosed?
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The diagnosis of the condition is made through detailed history taking and a thorough physical examination of the newborn.
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The familial history of the patient is assessed.
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Clinical presentation of the condition varies from one baby to another. The diagnosis of the condition is made by assessing the symptoms of the patients.
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The clinician may perform various laboratory tests to assess the patient.
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Radiographic imaging studies are performed to assess skeletal anomalies.
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Radiographic findings may reveal craniosynostosis, poor mineralization of the skull, bell-shaped chest, undeveloped collarbone and pubic bone, various extents of bending of long bones, and prominent periosteum.
What Are the Complications of Bent Bone Dysplasia Syndrome?
The possible complications of this condition are:
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Continuous progression in the severity of the symptoms.
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The affected baby is stillborn (death of the baby before or during birth) in most cases.
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Affected babies fail to develop properly during the newborn period.
How Is It Treated?
Since it is a genetically inherited condition, there is no treatment for this syndrome. The affected child may be referred to a pediatric neurosurgeon or an orthopedic surgeon, depending on the symptoms of the patient. The prognosis of this condition is questionable and poor. Most of the affected babies are stillborn or pass soon after delivery. And the survivors of the condition live with a severely reduced standard of living.
Conclusion
Bent bone dysplasia syndrome is an uncommon condition characterized by various skeletal anomalies. The condition is genetically inherited in an autosomal dominant pattern. It has a diverse clinical presentation affecting multiple systems, and the extent of the symptoms differs from person to person. The diagnosis of this condition is made through radiological imaging studies. As of now, there is still no cure to treat this condition. However, research and studies are being conducted to evaluate the progress and treatment of the disease. Presence of familial history may undergo genetic counseling before planning a child to assess the risks of inheriting the disease. The expecting parents with a familial history of the condition are recommended for genetic screening regularly.
