1. Introduction

Melnick-Needles syndrome is amongst the rarest genetic diseases, which is evidenced by only about 100 documented cases described in the literature. It causes a number of somatic disorders that occur as a result of abnormalities in the development of the skeleton. John Melnick and Carl Needles in 1996 described the case of a family whose several members presented similar somatic symptoms resembling skeletal dysplasia. They put forward the thesis that this disease may have a genetic basis. Following a series of such analyzes by research teams, mutations in the FLNA gene (Filamin A) were identified as the main cause of Melnick-Needles disease. The FLNA gene encodes the flamine A protein, which is involved in the formation of the cytoskeleton. In addition, flamine A plays a very important role in building muscle structure. It combines with actin, which is one of the key proteins involved in the muscle movement. In Melnick-Needles syndrome, the FLNA gene is damaged. This results in the synthesis of flamine A with an altered function, which, while showing hyperactivity, causes disturbances in the functioning of the cytoskeleton [1].

The disease has X-linked dominant inheritance. It is enough for a mutation to occur on only one of sex chromosomes to cause symptoms of the disease. In men, the symptoms of the disease are much more severe, which is why most male children die shortly after birth. Often the disease is included in the so-called ear-palatal-digital disorders or is also referred to as Melnick-Needles osteodysplasia.

Abnormalities in the development of the cytoskeleton are manifested as a series of symptoms in the external appearance and functioning of tissues and organs of people suffering from this disease. A characteristic feature of this syndrome is the loss of hearing in patients due to improper formation of the auditory ossicles. In addition, there is an incorrect formation of the palate and bone disorders in the fingers and toes. Moreover, numerous abnormalities in the development of the bones of the viscerocranium contribute to the characteristic appearance and asymmetry of the patients' faces. Deformations include: exophthalmos due to shallow eye sockets, wide-set eyes, micrognathism and the lack of permanent tooth buds. The general physique includes short stature, scoliosis, partial joint dislocations, shortening of the forearms and phalanges, arched bending and splitting of the distal parts of long bones, underdevelopment of the ribs (so-called ribbon ribs), hip dislocations and deformities of the pelvis, gait disturbances, narrow shoulders and sometimes bone deficiencies. Disturbances in the functioning of the respiratory and circulatory systems may also occur, including heart defects and lung infections, and there are also ureteral strictures and skin symptoms in the form of excessive hair on the forehead ^[1][2][1-2].

Diagnostics is based on a physical and radiological examination, family history and prenatal examinations. Melnick-Needles syndrome is an incurable disease, however, through multidisciplinary cooperation and treatment, it is possible to significantly improve the external appearance and quality of life of patients ^[2][3][2-3].

Therefore, the authors would like to present a case of a surgical correction of the facial skeleton in a 26-year-old female patient. Treatment was conducted in a multi stage manner consisting of distraction osteogenesis procedure followed by upper jaw surgery in order to improve the facial features and the functioning of the oral cavity and nasopharynx. The authors emphasize that such a method of treatment has not been (practiced) described in the literature so far.

2. Case Rreport

A 26-year-old patient came to the local Orthognathic Surgery Clinic for consultation and treatment of the maxillofacial defect that occurred in the course of abnormal cytoskeleton development, caused by a mutation in the FLNA gene in Melnick-Needles syndrome. Detailed radiological diagnostics, physical examination and family history were performed. In the family, there was one case of the disease in the maternal grandmother. Physical examination revealed an abnormal bite (overshot bite) caused by retraction and an abnormal shape (micrognathism) of the mandible and an abnormal arched palate with mucosal hyperplasia. The second skeletal class was noted. The patient complained of significantly reduced exercise capacity, sleep disturbances. The patient also reported difficult eating of hard food, the pronunciation of some vowels, snoring and frequent infections of the upper respiratory tract. Radiological examinations revealed: abnormal shape and reduced dimensions of the mandible and jaws, oligodontia in the mandible and jaws (no tooth buds 18,17,15,12,22,24,25,27,28,38,37,35,34,45,47,48), as well as persistent deciduous teeth (55,52,64,65). The baseline condition is shown in Figures 1-6. Laboratory tests revealed about 10 million erythrocytes, and the polysomnography showed AHI -45.

The patient was then presented with a detailed treatment plan, which she fully accepted. After orthodontic preparation (permanent upper and lower metal arches), surgical treatment under general anesthesia was performed. In the first stage, a bilateral transverse osteotomy of the mandibular bodies was performed using intra- and extraoral access, with the sparing of the inferior alveolar nerves and their mental branches. Then, on the outer surface of the bone, two individually designed mandible distractors were attached to the outer surface of the bone and the wounds were treated in a typical manner. After twelve days, as a result of a technical fault causing incorrect force of the left side distractor, it was replaced and the new distractor was fixed in the same place with emergency screws. Distraction began after 7 days and a bone lengthening of approximately 20 mm was achieved within 6 weeks. In the next stage, after a period of about 7 months after consolidation of the newly formed bone, the distractors were removed. On the left side, due to complications related to the defective functioning of the first distractor, additional stabilization in the distraction scar was preventively performed with a double titanium plate fixed with five typical screws ø 2.0 mm. In addition, the Le Fort I type osteotomy of the maxilla was performed in a typical manner and stabilized with dedicated ø 2.0 mm plates (Medartis^®), leading to the achievement of skeletal class I. In addition, left jaw corticotomy was performed in section 22-24 and augmentation with MP3 biomaterial (Osteobiol^®). In the final stage, a mandibular osteotomy in the mental section was performed as a genioplasty for aesthetic reasons. Every steps of the surgery are shown in figures 7- 16.Wound dressing, post-operative care and pharmacological treatment were carried out according to the usual routine. The final effects of the orthognathic treatment were assessed after 12 weeks. The patient fully accepted the effects of the reconstructive surgery. She is under the regular control of our facility. Further stages of the reconstruction of missing teeth, smile aesthetics, and occlusal correctness are currently carried out in the mock-up technique. The final results are shown in figures 17-19.

3. Discussion

Multidisciplinary treatment of patients suffering from Melnick-Needles syndrome allows for a significant improvement in their quality of life in everyday functioning. In terms of the facial part of the skull, the multifaceted cooperation of doctors of various specialties allows for very good results in improving the functioning of the stomatognathic system, aesthetic correction of facial features, as well as improving the functioning of the respiratory system, sleep function, and thus comprehensive improvement of general health. In the presented case, an uncompromising and effective change in the shape of the patient's face was achieved thanks to the performance of double jaw osteotomy, preceded by distraction osteogenesis of the mandible. The patient described the final result of the surgical treatment as very good and satisfying. In addition, orthodontic preparation before surgery was of no small importance here. It is also significant that so far no one has treated maxillofacial defects in patients with Melnick-Needles syndrome in a similar way.

In addition, various correction methods are widely practiced using the techniques of orthognathic surgery, orthodontics and implantology. Thus, the group of Kustrzycka D, based on the analysis of the literature and observation of their own case, recommends orthodontic treatment in conjunction with mandibular distraction if micrognation occurs in the course of the syndrome. In addition, the authors consider orthodontic treatment alone to be insufficient to restore the proper functioning of the stomatognathic system. According to the above, genetic tests may also be helpful in differentiating Melnick-Needles dysplasia from, for example, Frank-Ter Haar's disease, in the course of which similar clinical symptoms occur [4]. In addition, orthognathic surgery procedures are sometimes performed to eliminate life-threatening disorders and restore the proper functioning of vital organs and systems. This is confirmed by the work of the Molina FM team. The described case concerned a patient with severe respiratory disorders that required the creation of a permanent trachestomy in order to allow breathing. However, despite this approach, sleep apnea and pulmonary inflammatory infections were not eliminated, which resulted in frequent reconnection of the patient to a ventilator. Anterior distraction of the mandible was performed, reducing the skeletal class II. The distraction lasted 34 days, with the daily repositioning of the distractor arms by 1 mm. Although interesting for the patient seems to be the prolonged consolidation time of the newly formed bone (255 days), thanks to the distraction procedure, the tracheostomy was closed and sleep apnea was eliminated, and the frequency of lung infections was reduced [5]. The report by Aoki and Prahl-Andersen also confirms the effectiveness of the use of osteodistraction in an incorrectly developed mandible in dysplastic syndromes. The paper presents the effectiveness of osteodistraction in other genetic diseases, where the micrognathism significantly impairs breathing, forcing the decision of a permanent tracheostomy. Intraoral distraction and mandible protrusion eliminate this unpleasant necessity and restore the normal functioning of the upper respiratory tract [6].

Early detection of the disease also allows for possible further planning of multi-specialist treatment. Hearing impairment may be one of the early symptoms. Rapid implementation of radiological examinations when detecting hearing disorders is suggested by the JC Belfield team. They described the case of a girl who was diagnosed with hearing deterioration in the period from 6 months to 5 years, when her hearing was completely lost. During the development of the patient, progressive disturbances in the formation of the temporal bones and the cranial vault were confirmed radiographically. Moreover, at the same time there was a bilateral underdevelopment of anatomical structures within cochleas, which, according to the authors, had not been described until 2007 [7]. Chi-Hoon O et al. Also described three women (mother and two daughters) with symptoms of Melnick-Needles syndrome. The presence of the disease was confirmed in a family history. The researchers paid particular attention to a 16-month-old girl who, in addition to retardation in mental development and frequent pneumonia, experienced various typical orthopedic disorders. Among other things, the diagnosis was arched lower limbs, a flattened chest, ribbon-like ribs and numerous pelvic anomalies (underdevelopment of the ischial and pubic bones). Mutation of the FLNA gene was confirmed in all three women [8].

4. Conclusion

It should be emphasized, based on the presented case and the literature on the subject, that orthognathic surgery procedures give excellent therapeutic effects in patients suffering from Melnick-Needles syndrome. Thanks to the double jaw surgery, which has not been practiced so far, the patient achieved a significant improvement in the functioning of the upper respiratory tract and a change in facial features. In the literature and descriptions, the procedure

only a few cases of mandibular distraction in the presence of micrognations can be found surgically. An alternative to osteodistraction in the mandibular area may be BSSO. However, attention should be paid to the limitations of BSSO resulting from the relatively small protrusion of the mandibular body compared to the possibilities of osteodistraction. Other restrictions on BSSO result from a very unusual and delicate structure of the mandible, especially around the angle and ramus which increases the procedure difficulty and leads to unpredictability of osteotomy. Such a picture was ,,,, in the presented case, where the unusual structure of the mandible forced the use of individually designed distractors. It is possible to consider alternative methods of surgical treatment in relation to the presented method. One of such ideas the authors would like to share is the simultaneous osteodystraction of the maxilla and the mandible with the use of a RED distractor within the maxilla and individual distractors in the mandible. With such a procedure, however, another procedure cannot be ruled out - at least within the jaw, in order to match the short-circuit contacts.

In the presented procedure, the Le Fort I osteotomy allowed for an additional improvement in the appearance of the middle and lower levels of the face in relation to each other and the effective achievement of the 1st skeleton class. The diagnosis and diagnosis of the disease itself is not easy due to the rarity of its occurrence and the relatively small number of available case reports. Moreover, the significant symptoms of Melnick-Needles syndrome, especially in the maxillofacial area, may in a way induce surgeons to take up new challenges and apply innovative methods of reconstructive treatment.

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