Abstract
Diamond Blackfan Anemia (DBA) is a rare, congenital, hypoplastic anemic syndrome, which frequently presents with accompanying facial and bodily anomalies that require corrective surgery. We describe a 19-year-old girl with DBA, who presented at our department of Oral and Maxillofacial Surgery with a class II malocclusion and an anterior open bite. The treating orthodontist referred her for a combined orthodontic-orthognathic treatment plan. DBA is an uncommon hematologic disorder, which is mostly heritable in an autosomal dominant fashion with variable penetrance. Not all etiological factors can be entirely explained. Patients with this disease often experience severe hematological anomalies and physical abnormalities and the condition might require multiple transfusions and corticoid therapy. Both congenital aberrations and potential treatments can complicate surgery. Therefore, several considerations should be taken into account. Orthognathic surgery in patients with DBA can be performed safely, when the patients are hematologically stable, and when DBA-associated organ impairment is limited. Under these conditions, these patients can be treated with the same surgical and pharmacological procedures as those applied in healthy individuals.
Highlights
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DBA is associated with an elevated risk of craniofacial anomalies possibly necessitating orthognathic surgery.
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A hematological checkup, airway examination and evaluation of organ function should be conducted before performing surgery.
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Orthognatic surgery can be performed safely when patients are hematologically stable and organ impairment is limited.
Introduction
Diamond Blackfan anemia (DBA) is a rare, congenital, hypoplastic anemia that was first described by the American pediatricians Diamond and Blackfan, in 1938 [ ]. DBA is estimated to occur in 1 out of 100,000 to 200,000 live births [ ], and it typically presents within the first year of life, although presentation in adulthood has also been described [ ]. The inheritance pattern is mostly autosomal dominant, with a variable penetrance. Some genes are inherited in an X-linked pattern, which can explain the heterogeneous character of the disorder [ ]. In addition to the hematological complications, patients often have facial anomalies, which require orthognathic surgery. Here, we describe a patient with severe hematological and maxillofacial abnormalities.
Presentation of case
A 19-year-old girl was referred to the department of Oral and Maxillofacial Surgery by a treating orthodontist. She presented with vertical maxillary hyperplasia and protrusion of the upper lip, which resulted in a gummy smile. She displayed an Angle class II malocclusion with an anterior open bite and eversion of the lower incisors ( Fig. 1 ). A further clinical examination showed normal sensitivity in the teeth and radiography showed pulp stones in elements 36 and 46 (shown on the panoramic radiograph, Fig. 2 ). The patient had no history or clinical signs of a disorder in the temporo-mandibular joint.
Overall, we noted that the size of the patient’s head was disproportional to the body, with frontal bossing, and a flat nasal bridge ( Fig. 3 ). A computed tomography of the skull showed that the cranial bones were substantially wider than normal, which could indicate extramedullary hematopoiesis ( Fig. 2 ).
The patient’s medical history included congenital dyserythropoietic anemia. As a child, she had had multiple blood transfusions, until a splenectomy was performed, at age 8 years. A cholecystectomy was performed one year later. The patient was scheduled for routine follow-ups with her general practitioner and hematologist. Excess iron storage throughout the body was treated with iron chelation therapy, which showed good effects.
Due to her splenectomy, she received amoxicillin 250 mg twice daily. Her platelet count was elevated, to values above 1000 × 10 9 /L (normal values: 150–400 × 10 9 /L). This condition could be attributed to post-splenectomy thrombocytosis, which was treated with 80 mg aspirin daily. The patient was also followed up regularly for a minor cardiac dilatation, due to chronic anemia, without hemodynamic repercussions. She had a history of poor wound healing. However, four impacted wisdom teeth were removed 6 months earlier, and recovery was uneventful.
Up to the moment of presentation at our institute, the patient had no diagnosis of a possible genetic disorder. However, due to the unusual combination of her hematological condition and the intra-oral and extra-oral clinical observations, we set up a collaboration with the Department of Human Genetics at our institute, to identify the genetic anomaly. This specific array of symptoms pointed towards a possible diagnosis of Diamond Blackfan anemia. A microarray analysis showed a 404-kb duplication in genes GABRA6 , GLRXP3 , and GABRA1 , located in chromosomal region 5q34.
To improve the occlusion, aesthetics, and oral function, a combined orthodontic-orthognathic treatment plan was proposed. The patient was cleared for surgery after a hematological workup. No contra-indications were found for surgery or for the postoperative use of antibiotics, nonsteroidal anti-inflammatory drugs, or other analgesics. First, extraction of elements 14 and 24 and placement of bone anchors in the upper jaw would allow the orthodontist to retrude the upper front teeth and perform presurgical orthodontic decompensation. Next, a bimaxillary osteotomy is to be performed to correct dentoskeletal discrepancies. Finally, orthodontic finishing is needed to establish the final occlusion.
Discussion
DBA is a congenital, pure red-cell aplasia that displays genetic and clinical heterogeneity. The DBA diagnosis is based on clinical and laboratory diagnostic criteria ( Table 1 ). Moreover, a large number of patients that fall outside these criteria might be diagnosed with a ‘non-classical’ DBA [ ]. DBA is associated with an elevated risk of congenital malformations and a predisposition to cancers, such as acute myeloid leukemia and osteosarcoma [ ]. Current treatment options consist of corticosteroid therapy, blood transfusions, and hematopoietic stem cell transplantation [ ].
