Case Report

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Case Report A Case of Klippel-Feil and Turner Syndromes Jae Hyun Park, DMD, MSD, MS, PhD1

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Kiyoshi Tai, DDS, PhD2

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Yasumori Sato, DDS, PhD3

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Akiyoshi Nishiyama, DDS4

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Je-Won Shin, DMD, MSD, PhD5

Abstract: The purpose of this paper was to describe the clinical case of a 12-year-old female patient with Klippel-Feil syndrome (KFS) combined with Turner syndrome (TS) and a submucous cleft palate (CP). The patient’s general appearance was characterized by KFS, a clinical triad consisting of congenital fusion of at least 2 of 7 cervical vertebrae with a short neck, limited head motion, and a low posterior hairline. Three-dimensional images from cone-beam computed tomography (CBCT) revealed cervical vertebrae anomalies and submucous CP. It was reported that the patient had TS and has been administered growth hormone (GH) therapy. Due to a skeletal Class III pattern with a steep mandibular plane angle, facial asymmetry, and fused cervical vertebrae, GH’s effects on the craniofacial complex should be considered before orthopedic/orthodontic treatment is started. (Pediatr Dent 2012;34:e35-e39) Received December 20, 2010 | Last Revision January 8, 2011 | Accepted February 10, 2011 KEYWORDS: KLIPPEL-FEIL SYNDROME, TURNER SYNDROME, SUBMUCOUS CLEFT PALATE, GROWTH HORMONE, ORTHODONTIC TREATMENT

Klippel-Feil syndrome (KFS) was reported by Klippel and Feil.1 It is characterized by a congenital fusion of at least 2 of 7 cervical vertebrae in the cervical spine, which results in a short neck, limited head motion, and a low posterior hairline.2 KFS has been classified into 3 categories: type 1 is a massive fusion of the cervical spine; type 2 is when 1 or 2 vertebrae are fused; and type 3 is when there are thoracic and lumbar spine anomalies in association with type 1 or type 2 KFS.3-7 Abnormalities associated with KFS may include: scoliosis; spina bifida; cleft lip and palate (CLP); frontonasal malformation; facial asymmetry; anomalies of the kidneys and ribs; deafness; respiratory problems; and congenital heart disease.8-10 In some cases, there may be neurological complications due to associated spinal cord injury.10 The incidence of KFS is estimated to be 1:40,000 to 1:42,000, with 60% of the cases occurring in females.11 In most KFS patients, the etiology and its associated conditions are unknown; however, in some cases, KFS may be inherited as an autosomal dominant or autosomal recessive trait. The syndrome can present with a variety of other clinical syndromes, including fetal alcohol syndrome, Goldenhar syndrome, or anomalies of the extremities.10-12 In the course of their practices, dentists may incidentally encounter cervical spinal anomalies associated with KFS during their radiological examinations. Since KFS is mainly characterized

by the fusion and occasional agenesis of some parts of 2 or more cervical vertebrae, it typically affects the natural head and neck position. This may, in turn, cause alternations in the craniofacial development.8-10 Long-term follow-up of KFS patients is essential to understanding the craniofacial development phases.8-10,13 Turner syndrome (TS) is an X chromosome genetic disorder that occurs in approximately 1 in every 2,500 live female births. Loss of all or part of an X chromosome causes TS.14,15 It is commonly characterized by abnormalities such as shortness of stature, epicanthal folds, low posterior hairline, a short webbed neck, and cubitus valgus.14,16 Girls with TS typically experience gonadal dysfunction, congenital heart disease, hypothyroidism, diabetes, vision problems, hearing concerns, and other autoimmune diseases.14-17 Shortness of stature has a psychological and sociological impact in childhood, adolescence, and adulthood and is, therefore, a driving force behind the use of a growth hormone treatment in TS cases. According to Rosenfeld et al.,18 while girls with TS are generally not growth hormone (GH) deficient, they do grow in response to a supplemental growth hormone administration. The purpose of this case report was to present a clinical case emphasizing the importance of a multidisciplinary approach in the detection and diagnosis of multiple syndromes.

Case report 1Dr. Park is an associate professor and chair, Postgraduate Orthodontic Program, Ari-

zona School of Dentistry and Oral Health, A.T. Still University, Mesa, Ariz, and an international scholar, Graduate School of Dentistry, Kyung Hee University, Seoul, Korea. 2Dr. Tai is a visiting adjunct assistant professor, Postgraduate Orthodontic Program, Arizona School of Dentistry and Oral Health, A.T. Still University, and an adjunct assistant professor, Graduate School of Dentistry, Kyung Hee University, Seoul, Korea and is an orthodontist in private practice; 3Dr Sato is an orthodontist; and 4Dr. Akiyoshi Nishiyama is a lecturer, Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, all in Okayama, Japan. 5Dr. Shin is a professor and chair, Department of Oral Anatomy and Developmental Biology, Graduate School of Dentistry, Kyung Hee University, Seoul, Korea. Correspond with Dr. Park at [email protected]

A 12-year-old female patient with documented KFS, TS, and submucous cleft palate (CP) was referred for orthodontic treatment to the orthodontist by her pediatrician. According to the physician, the following conditions were reported but were not, apparently, inheritto from her parents: hearing loss; hydronephrosis; Fallot tetralogy; ventricular septal defect; and an enlarged right ventricle. A physical examination revealed that she had a short neck with limited movement and a low posterior hairline—all primary characteristics of KFS. She was short of stature and had epicanthal folds, a short webbed neck, and cubitus valgus,

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characteristics of TS. On the basis of molecular analysis, she had a 45,XO karyotype. Her height (125.7 cm/ 49.5 inches) was below the third percentile for girls her age, even though a GH has been administered daily from the time she was 10-years, 5-months-old (Figure 1).19 No mental retardation was apparent. She had a facial asymmetry with thick protrusive lips (Figures 2 and 3). An intraoral examination revealed the mixed dentition stage with Class III molar occlusion on the left side and Class I molar occlusion on the right side. All erupted permanent anterior teeth and first molars showed discoloration. This patient was born with significant medical problems. Multiple medications were taken and adjusted over her childhood. Her mother could not remember whether she had taken tetracycline during her pregnancy, however, her health issues and a combination of medications taken as a result of the health problems are suspect for involvement in the staining. The patient showed an anterior cross bite and unilateral posterior crossbite.

When her mandible was guided in centric relation, a functional shift was detected because of the presence of crossbites. She had a 2-mm overjet and 20% overbite. Her mandibular dental midline was shifted to the right side approximately 7.5-mm (Figure 4). A submucous CP was identified by the presence of a bifid uvula, a furrow along the midline of the soft palate, and a notch at the back of the hard palate (Figure 5).20 She also had associated speech problems, persistent ear disease, and swallowing difficulties. A panoramic radiograph revealed the maxillary left canine to be horizontally impacted (Figure 6a). Cephalometric analysis using a lateral cephalogram showed Class III skeletal pattern (ANB: -7.7°, Wits: -13.3 mm) with a hyperdivergent growth pattern (SN-GoG n: 38.8°). The maxillary incisors were proclined (U1 to SN: 114.6°) and the mandibular incisors were retroclined (IMPA: 84.1°; Figure 6b). Examination of the lateral cephalogram from the patient revealed anomalous cervical vertebrae in the cervical spine. The shape of her spinous processes and vertebral bodies clearly differed from that of a normal 12-year-old girl (Figure 7). The shape of her spinous processes and vertebral bodies in the cervical vertebrae were obscure and appeared to be fused. We referred her to an orthopedic specialist for a detailed examination of her cervical vertebrae. Three-dimensional (3-D) reconstructions from computed tomography (CT) verified the diagnosis of KFS. She was also found to have scoliosis and Sprengel’s deformity.11,21 Figure 8 shows a 3-D reconstruction from the CT of the patient’s cervical vertebrae. Her cervical vertebral bodies could not be clearly distinguished from each other because of the anomalies in the spinous processes of all her cervical vertebrae. She did not require any therapy at this point in her life, since she had no real difficulties, but her family was advised to take her for periodic examinations due to the possibility that clinical manifestations associated with the neurological disorder might arise later.

Discussion Figure 1. Height growth curve for the patient with Klippel-Feil and Turner syndromes.

Figure 2. Facial photographs of a patient with Klippel-Feil and Turner syndromes.

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Both and KFS and TS occur infrequently, with KFS being the most rare, so the likelihood of encountering a patient with both conditions is low. Also, KFS patients present at different ages with varying clinical anomalies, and, thus, individual patients require individualized care. The challenge for the clinician is to recognize the associated conditions that can occur with KFS. The radiographic appearance of congenital anomalies of the cervical vertebrae encountered in patients with syndromes and nonsyndromic and idiopathic conditions has been described in various studies. 3,4,22 Anomalous cervical vertebrae have been identified on 2-dimensional (2-D) cephalometric radiographs. Although 2-D sagittal lateral cephalograms can provide a reference for observing the shape changes of cervical vertebrae at various stages of growth, conebeam computed tomography (CBCT) could be used as an adjunctive diagnostic tool for a 3-D visualization of cervical vertebral morphology.

PEDIATRIC DENTISTRY

Block vertebrae (failure in segmentation) are a general feature of KFS. 3 With KFS, the most common feature is a blocking or fusion of cervical vertebrae and the resulting reduction in length of the cervical spine and shortening of the neck.

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Although KFS is present from birth, the radiographic findings may be progressive.23-25 The fusion between cervical vertebrae C1 and C2 tends to develop during the first decade of life, while fusion between cervical vertebrae C2 and C3 is related to

Radiographs and intraoral photograph of a patient with Klippel-Feil and Turner syndromes ( Figures 3-6 )

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4

5

6a

6b

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Figure 3. Posteroanterior cephalogram showing facial asymmetry, a characteristic short neck, and shoulder asymmetry. Figure 4. Intraoral photograph. Figure 5. Multiplanar reconstruction (MPR) image from a computed tomography scan showing submucous cleft palate. Figure 6. (a) Panoramic radiograph showing a horizontally impacted maxillary left canine. (b) Lateral cephalogram showing anomalous cervical vertebrae in the cervical spine. Figure 7. A normal girl the same age as the patient in the present case. C1–C7 indicates the first through seventh cervical vertebrae.


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a

c

b

Figure 8. Three-dimensional reconstruction images of a patient with Klippel-Feil and Turner syndromes. A computed tomography scan of the patient’s cervical vertebrae: (a) right; (b) posterior; (c) lateral view.

neurological symptoms in the third decade.26 Most symptoms, regardless of the location of the lesion, appear before age 30. Compared with other syndromes, a careful differential diagnosis of KFS is needed, since many other syndromes may present fusion of the cervical vertebrae as a part of their clinical features. If the fetus has a cervical vertebrae fusion, the mandible will remain compressed against the chest, forcing the tongue to lie between the fusing palatal shelves, resulting in incomplete closure of the palate.27 Studies have reported that the frequency of congenital vertebral fusion is higher in children having CLP or CP than in noncleft controls.26,28 The high prevalence of CP in patients with congenital vertebral fusion indicates the developmental interactions by which a primary defect in one organ system can lead to secondary defects in contiguous structures.26 Dentists should be aware of the abnormalities of KFS before treatment planning. They should check for the existence of a submucous CP and the possibility of congenitally missing teeth and tooth size imbalances using the Bolton index.9 One other important consideration with KFS patients is an associated difficulty in posturing their heads and necks due to their reduced mobility, making many normal dental procedures more difficult. Likewise, the patient’s inability to completely open their mouth affects every aspect of working on them. It is difficult to take panoramic radiographs because of the shortness of their neck, which hinders normal rotation of the radiographic machine.13 Should intubation of patients with KFS be necessary, there is an added challenge and special precautions. During laryngoscopy, intubation, and positioning, there is high risk of neurological damage because the patient has potential cervical instability.29 When positioning the patient to provide maximum access to their oral cavity, it is especially important to exercise care to avoid any cervical damage, particularly if they will require dental treatment/management in an operating room. The skeletal characteristics of TS are decreased maxillary growth with a hypoplastic midface and a wide and micrognathic mandible. Some studies have demonstrated that orthodontic treatment is best delayed until treatment has been completed in patients receiving GH therapy due to their unpredictable mandibular growth.30,31 Hass et al.,14 reported that, even when

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there have been increases in statural height in TS children treated with human GH, there was little or no effect on the growth of their jaws, particularly in the older patients. They also stated that, if TS children require considerable improvement in craniofacial development, GH treatment would need to be initiated early (before the cessation of growth at the synchondroses of the cranial base) for the treatment to be effective.14 In typical TS patients, Class II dental and skeletal relationships, lateral crossbite, and anterior open bite have frequently been reported.14 Common intraoral findings include posterior crossbite, high narrow palatal arch, tooth size imbalance, an increased idiopathic root resorption tendency, and early eruption of the permanent teeth.32 In this case, the patient had a hyperplastic mandible, so the GH therapy necessary to accelerate height growth would negatively affect her orthodontic treatment. To determine the proper treatment plan in such cases, the effects of the GH treatment on the craniofacial complex must be considered. In addition, further investigation into the effects of GH therapy on tooth movement during orthodontic treatment as well as on facial growth is necessary. The pediatric dentist may be one of the first clinicians to detect and report anomalies or syndromes in their patients. It is, therefore, important that they are aware of this unusual case and that they discuss their observations with the patient’s family and other specialists. In this way, they fill an important position on the interdisciplinary team that will provide valuable information for the management, diagnosis, and treatment options of children with such conditions.

References

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