Binder-type nasomaxillary dysplasia also known as binder’s syndrome is a rare developmental defect that is present at birth (congenital) and characterized by a retruded mid-face with an extremely flat nose maxillofacial dysplasia whose noses were corrected with only costal cartilage grafts using a combined oral vestibular and external rhinoplasty approach for nasal dorsal augmentation, columellar lengthening, and premaxillary augmentation. The disorder is characterized by the underdevelopment (hypoplasia) of the central portion of the face, particularly the area including the nose and upper jaw (maxillofacial region). Binder reported three cases and six characteristic features[rx]:
- (1) carcinoid face;
- (2) abnormal position of the nasal bones;
- (3) Intermaxillary hypoplasia with consecutive malocclusion;
- (4) reduced or absent anterior nasal spine;
- (5) atrophy of the nasal mucosa, and
- (6) absence of the frontal sinus (not obligatory).
The specific symptoms and the severity of the disorder can vary from one person to another. Characteristic symptoms include an abnormally short, flattened nose and underdevelopment of the upper jaw bone (maxillary bone). The exact cause of Binder syndrome is not fully understood. Most cases appear to occur sporadically, but familial cases have been reported as well. Surgical and orthodontic treatment is recommended.
Binder-type nasomaxillary dysplasia was first described in the medical literature as far back as 1882. Dr. Noyes described the essential features of a single patient in 1939. Dr. von Binder first identified the condition as a distinct clinical entity in 1962 in a comprehensive report on three children; the disorder now bears his name. There is some debate in the medical literature as to whether Binder-type nasomaxillary dysplasia is a syndrome or an association. A syndrome is typically a genetic disorder, in which a group of symptoms consistently occur together. An association is a nonrandom collection of birth defects that may have been caused by several factors, including genetic ones, and can potentially be associated with a variety of underlying conditions.
Symptoms
Although researchers have been able to establish characteristic or “core” symptoms, much about Binder-type nasomaxillary l dysplasia is not fully understood. Several factors including the small number of identified affected individuals, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing an accurate picture of associated symptoms and prognosis.
The characteristic finding of the disorder is the abnormal development (dysplasia) of the central or mid-portion of the face. The midface appears abnormally flattened. In some patients the frontal sinuses may be underdeveloped or absent. Affected individuals have a short nose and flattened bridge of the nose. The nasal bones may be underdeveloped or abnormally positioned. The bottom of the sheet of cartilage and bone (nasal septum) that separates the right and left nostrils is known as the columella. The columella is abnormally short and the nostrils have a half-moon or comma-shaped appearance. In cases where the columella is severely short, the nostrils may appear triangular. The upper lips may be slanted backward. Despite the various nasal abnormalities, the sense of smell is unaffected.
Underdevelopment (hypoplasia) upper jaw (maxillary bone) is another key feature of Binder-type nasomaxillary dysplasia. The maxillae are the large bones of that form the upper jaw and assist in the formation of the nasal cavities, the bony cavities of the eyes (orbits), and the roof of the mouth (palate). The maxillae also contain the sockets of the upper teeth. Hypoplasia of the upper jaw may cause the lower jaw (mandible) to appear to protrude or stick out (relative prognathism). However, in some individuals, the mandible may actually be longer than normal (true prognathism). Affected individuals also develop malocclusion, a condition in which the upper teeth are improperly positioned about the lower teeth. More specifically, affected individuals may be predisposed to a reverse overbite (class III malocclusion), in which the lower jaw is too far forward, the cusps of the lower back teeth are abnormally positioned in front of the corresponding upper teeth, and the lower front teeth (incisors) meet or lie in front of the corresponding upper incisors.
In some cases, additional symptoms and physical findings have been reported in association with this condition. Individuals with Binder type nasomaxillary dysplasia seem to be at an increased risk of various malformations of the spine (vertebrae). Less often, affected individuals exhibit hearing impairment, incomplete closure of the roof of the mouth (cleft palate), misalignment of the eyes (strabismus), and structural malformations of the heart (congenital heart defects), mild intellectual disability, and other features. However, the exact relationship between these findings and Binder-type nasomaxillary dysplasia is unknown and they may not represent symptoms of the disorder.
Causes
The exact, underlying cause of Binder-type nasomaxillary dysplasia is not fully understood. In many cases, the disorder is believed to occur spontaneously, for no apparent reason (sporadically). However, there have been reports in the medical literature of families in which more than one family member was affected. This suggests that genetic factors play a role in some affected individuals. Some researchers have suggested that Binder-type nasomaxillary dysplasia is a genetic disorder inherited in either an autosomal dominant or recessive manner. Other researchers have suggested that the disorder is caused by complex genetic factors, specifically the interaction of many different genes, possibility in combination with environmental factors (multifactorial inheritance).
Researchers have identified several environmental factors that may be associated with Binder type nasomaxillary dysplasia including birth trauma, vitamin K deficiency, or exposure of a developing infant to an anti-seizure drug known as Phenytoin or to an anti-blood-clotting (anticoagulant) drug known as warfarin. No suspected environmental agent has been conclusively linked to Binder type nasomaxillary dysplasia.
Some researchers believe that specific cases of Binder type nasomaxillary dysplasia may be mild forms or variants of chondrodysplasia punctata (CDP), a general term for a group of disorders characterized by abnormalities affecting the development of cartilage and bone (skeletal dysplasias). A variety of additional symptoms and physical features can develop. A characteristic finding of CDP is the formation of small, hardened spots of calcium on the “growing portion” or heads of the long bones (stippled epiphyses) or inside other areas of cartilage in the body. However, over time there is a loss of epiphyseal stippling. Individuals who receive a diagnosis of Binder type maxillofacial dysplasia until their teen-age years or older may actually have CDP, but the distinctive epiphyseal stippling is gone so that a diagnosis of CDP is not considered.
Diagnosis
A diagnosis of Binder syndrome is based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation. Certain specialized tests can be used to confirm the diagnosis.
Clinical findings
- Abnormally large, wide-open fontanelles at birth that may remain open throughout life. The wide-open metopic suture results in the separation of the frontal bones by a metopic groove. The forehead is broad and flat; the cranium is brachycephalic.
- Frontal and parietal bossing and mid-face retrusion
- Narrow, sloping shoulders that can be opposed at the midline due to clavicular hypoplasia or aplasia
- Abnormal dentition includes delayed eruption of secondary dentition, failure to shed the primary teeth, variable numbers of supernumerary teeth along with dental crowding, and malocclusion
- Hand abnormalities including brachydactyly, tapering fingers, and short, broad thumbs
- Short stature (typically moderate)
- Normal intellect in individuals with classic CCD spectrum disorder
Shoulders in an individual with clavicular hypoplasia may be brought to the midline.
Radiographic findings
- Cranium
- Wide-open sutures, patent fontanelles, presence of wormian bones (small sutural bones)
- Delayed ossification of the skull
- Poor or absent pneumatization of the paranasal, frontal, and mastoid sinuses
- Impacted, crowded teeth; supernumerary teeth
- Thorax
- Cone-shaped thorax with narrow upper thoracic diameter
- Typically bilateral (but not necessarily symmetric) clavicular abnormalities ranging from complete absence to hypoplastic or discontinuous clavicles. The lateral portions are more affected than the medial aspects of the clavicles.
- Hypoplastic scapulae
- Pelvis
- Delayed ossification of the pubic bone with wide pubic symphysis
- Hypoplasia of the iliac wings
- Widening of the sacroiliac joints
- Elongated femoral head with short femoral neck and elongated epiphyses (“chef-hat” appearance)
- Coxa vara
- Hands
- Pseudoepiphyses of the metacarpal and metatarsal bones, which may result in a characteristic lengthening of the second metacarpal
- Hypoplastic distal phalanges
- Deformed and short middle phalanges of the third, fourth, and fifth digits with cone-shaped epiphyses
- Other. Osteopenia/osteoporosis with evidence of decreased bone mineral density by DXA; some affected individuals sustain multiple fractures.
Molecular testing approaches can include single-gene testing, karyotype, or the use of a multigene panel:
- Single-gene testing. Sequence analysis of RUNX2 is performed first and followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found.Note: Gene-targeted methods will detect deletions ranging from a single exon to whole genes; however, breakpoints of large deletions and/or deletion of adjacent genes may not be determined.
- Karyotype. If RUNX2 testing is not diagnostic and if strong suspicion persists in an individual with features of CCD spectrum disorder who also has multiple congenital anomalies and/or developmental delay, a karyotype may be considered to evaluate for complex chromosome rearrangements or translocations that involve 6p21.1 (RUNX2 locus) but do not result in RUNX2 copy number changes.
- A multigene panel that includes RUNX2 and other genes of interest may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition while limiting the identification of pathogenic variants in genes that do not explain the underlying phenotype. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
Clinical Testing and Workup
Specialized imaging techniques may be used to help obtain a diagnosis of Binder syndrome. Such tests include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues.
Such exams may yield specific findings including underdevelopment or absence of the bony protrusion that projects from the base of the nasal septum to join with the middle part of the upper jaw (anterior nasal spine); the thinness of a portion of the upper jaw known as the alveolar bone, which forms the dental arch over the upper incisors; underdevelopment or absence of the frontal sinuses; and/or certain abnormalities detected with cephalometric studies, which are scientific measurements of particular craniofacial dimensions.
Treatment
The treatment of Binder syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians or general internists, oral and plastic surgeons, craniofacial surgeons, specialists in the diagnosis, prevention, and treatment of crooked teeth (orthodontists), specialists in the diagnosis and treatment of disorders of the bones, joints, ligaments, and muscles (orthopedists), and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment. Psychosocial support for the entire family is essential as well.
There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with Binder syndrome.
Recommended treatment may include various orthodontic and surgical measures to help correct abnormalities of the jaw and nose. The specific therapeutic procedures performed will vary depending upon the nature and severity of the disorder in each individual including the specific anatomical abnormalities present, a patient’s general health, a patient’s age, patient preference, and other factors. Often more than one surgical procedure is necessary. The specific type and timing of an individual surgical procedure are determined based on disease severity and patient age. Some affected children have been treated during childhood, while others are not treated until the late teen-age years, which is when the bone stops growing.
Some individuals may only require treatment with orthodontic devices such as braces that can straighten teeth or reposition the jaw. Nose (nasal) reconstruction can be accomplished with bone or cartilage grafts, or the implantation of alloplastic materials. In some cases, the grafting of cartilage from the ribs has been used successfully to reconstruct the nose (costochondral graft).
More severe cases require surgical procedures known as Le Fort I or II osteotomy. During Le Fort, I osteotomy, the upper jaw is sectioned and repositioned to treat malocclusion and, if present, cleft palate. Le Fort II osteotomy involves repositioning the upper jaw and nose and correcting the backward displacement (retrusion) of the middle portion of the face.
Treatment of nasal deformity usually involves adding cartilage grafts to the bridge and to support the tip to give more projection and shape. These may be from the ear, but in most cases one needs more cartilage and the rib may be used. The narrow nasal passages may also require treatment.
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