American Journal of Medical Genetics 103:326 ±333 (2001)
New Syndrome? Hemifacial Myohyperplasia: Description of a New Syndrome Samson Lee,1 Raymond Sze,2 Craig Murakami,3 Joseph Gruss,4 and Michael Cunningham5* 1
Department of Otolaryngology, University of Washington, Seattle, Washington Children's Craniofacial Center, Children's Hospital and Regional Medical Center, and Department of Radiology, University of Washington, Seattle, Washington 3 Division of Otolaryngology, Virginia Mason Medical Center, Seattle, Washington 4 Children's Craniofacial Center, Children's Hospital and Regional Medical Center, and Division of Plastic Surgery, University of Washington, Seattle, Washington 5 Children's Craniofacial Center, Children's Hospital and Regional Medical Center, and Department of Pediatrics, University of Washington, Seattle, Washington 2
Hemifacial hypertrophy is a rare condition characterized by unilateral enlargement of all tissues of the face. We describe three patients who exhibit hemifacial hyperplasia of the muscles of facial expression with no other organ system involvement. These three cases, in addition to six other cases identi®ed in the literature, describe a unique constellation of characteristics that place these patients into a distinct syndrome. We suggest that the term ``hemifacial myohyperplasia'' be used to describe this speci®c and unique condition. ß 2001 Wiley-Liss, Inc.
KEY
WORDS: hemifacial; hypertrophy; hyperplasia; myohyperplasia INTRODUCTION
First described by Meckel [1822], congenital hemihypertrophy or hemihyperplasia is a rare condition. In the literature, this disease is most often described as hemihypertrophy rather than hemihyperplasia [Cohen, 1995]. We chose the term ``hemifacial myohyperplasia'' for our discussion of this condition because the condition involves muscle enlargement rather than muscle proliferation. Hemihyperplasia can involve an entire
*Correspondence to: Dr. Michael Cunningham, RR537-HSB, Department of Pediatrics, University of Washington, 1959 Paci®c St. NE, Box 356320, Seattle, WA 98159. E-mail:
[email protected] Received 30 January 2001; Accepted 15 June 2001 DOI 10.1002/ajmg.1578
ß 2001 Wiley-Liss, Inc.
side or an isolated part on one side of the body. In most of the cases described in the literature, hemihyperplasia involves all of the organ systems of the affected body part. There are several classi®cation systems for hemihyperplasia by Rowe [1962] (Table I) and Ward and Lerner [1947] (Table II). The ®rst case of isolated hemifacial hyperplasia was described in 1836 by Beck [1836]. Since then, over 50 cases of isolated hemifacial hyperplasia have been described in the literature. According to Rowe's de®nition of hemifacial hyperplasia, ``true'' hemifacial hyperplasia is characterized by unilateral enlargement of all tissues on one side of the face (e.g., skin, bone, nervous, cardiovascular, fat, etc.) while ``partial'' hemifacial hyperplasia would describe enlargement of one or more, but not all organ systems of the face [Kogon et al., 1984; Rowe, 1962]. In Ward and Lerner's classi®cation system, ``total'' hemifacial hyperplasia is characterized by hyperplasia of all organ systems of the face, while ``limited'' hemifacial hyperplasia would describe those cases that are limited to certain organ systems of the face. The vast majority of the cases of hemifacial hyperplasia described in the literature are classi®ed as ``true'' or ``total'' hyperplasia. In a select few cases, only the muscular system is involved in hemifacial hyperplasia, with no bony or other organ system hyperplasia evident [Staffenberg et al., 1998]. Our three patients demonstrate unilateral hyperplasia of the facial muscles with no evidence of hyperplasia of bone or other organ systems. The pattern of muscular involvement suggests a segmental pattern correlating to the derivatives of the 1st and 2nd branchial arches. We believe that our cases, combined with the previous cases cited in the literature, are a distinct entity from the previous classi®cations of hemifacial hyperplasia and should be categorized as a separately de®ned syndrome named hemifacial myohyperplasia.
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TABLE I. Rowe's Classi®cation of Hemihypertrophy Complex hemihypertrophy Involves an entire half of the body, or at least an arm, and a leg, wherin the enlarged parts may be (a) One the same side, or (b) Crossed Simple hemihypertrophy Involves a single limb Hemifacial hypertrophy (a) True hemifacial hypertrophy: characterized by unilateral enlargement of the viscerocranium, bounded superiorly by the frontal bone (not including the eye), inferiorly, the inferior border of the mandible, medially, by the midline and laterally by the ear including the pinna with enlargement of all tissues, teeth, bones, and soft tissue in this area. (b) Partial hemifacial hypertrophy if not all structures are enlarged to the same degree or not at all [Kogon et al., 1984] (Strafne and Lovestedt).
TABLE II. Ward and Lerner Classi®cation of Congenital Hypertrophy Total hypertrophy (involves all systems) Segmental Crossed Hemihypertrophy (entire side) Limited hypertrophy (in which one or more, but not all systems are involved) Muscular Skeletal Vascular Neurologic
CLINICAL REPORTS Patient 1 A 2-year-old female (Fig. 1) was referred to the Craniofacial Center (Children's Hospital Regional Medical Center, Seattle, WA) for marked left-sided facial asymmetry. Past medical history was signi®cant for a congenital ankyloblepharon of the left lateral eyelids repaired within the ®rst year of life. The family history was negative except for her father having had epilepsy as a child. On physical examination, gross asymmetry of the left face was noted. There was dimpling of the skin on the left side of the chin and left corner of the mouth. Enophthalmos of the left eye was present with a small palpebral ®ssure on the left compared to the right. The left lateral canthus was displaced inferiorly with minimal narrowing of the palpebral ®ssure. There was a slight ptosis of the left brow. The left nasal vestibule was smaller compared to the right. There was minimal malar ¯attening. The left pinna and external auditory canal were smaller than on the right side. There was a downward displacement of the left auricle. On intraoral examination it was noted that there was an overbite (Class II malocclusion) with crowded dentition of the left mandible. The chin was deviated to the left. The patient exhibited a paresis of the marginal mandibular and frontal branches of the seventh cranial nerve. The remainder of the physical exam was normal. A head and neck CT (Figs. 2 and 3) revealed enlargement of the muscles of facial expression (mentalis, depressor labii inferioris, buccinator, orbicularis, oris, zygomatic major and minor, nasalis, and levator labii superioris aleque nasi, orbicularis oculi, and platysma) on the left side. The posterior belly of the digastric was enlarged, while the anterior belly of the
digastric was normal. The muscles of mastication were normal. The muscle signal and density on all sequences were normal. There was evidence of mild left maxillary and mandibular hypoplasia as well as deviation of the
Fig. 1. Patient 1. AP photo. Note narrow palpebral ®ssure of the left eye, dimpling near the left oral commisure, inferiorly displaced auricle on the left side, ptosis of the left eyebrow, small nasal vestibule on the left side, and malar ¯attening of the left side.
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Fig. 2. Patient 1. Head CT. Note the nasal tip and frontal process of maxilla deviation toward the left. Note the hyperplastic zygomaticus (small white arrowheads) and levator labii superiorus alaquae nasi (large white arrowheads) muscles on the left compared to the normal corresponding structures on the right.
nasal bones and frontal process of the maxilla toward the left side. (Fig. 4). It was decided that a muscle biopsy might yield a more speci®c clinical diagnosis. The biopsy revealed normal appearing muscle on routine histology. Patient 2 A 9-year-old female (Fig. 5) was referred to the Craniofacial Center for marked right-sided facial asymmetry. Past medical history was signi®cant for a lingual vascular malformation on the right side removed by laser surgery. Family history was negative. On physical examination, gross asymmetry of the right face was noted. There was dimpling of the skin on the right side of the chin and right corner of the mouth. There was a mild right ptosis of eyelid, enophthalmos of right side, and a narrow palpebral ®ssure on the right side. A periocular mass thought to be a lymphangioma was present, pushing the lower right eyelid superiorly. There was a slight downward displacement of the right auricle. The right nasal vestibule was slightly smaller then the left. There was malar ¯attening on the right side. Oral examination revealed a class II malocclusion with a small overbite. The chin was deviated to the right. An examination of the cranial nerves was normal. The remainder of the physical exam was normal.
Fig. 3. Patient 1. Head CT. Note the nasal bone and ethmoidal air cell deviation toward the left. Note the hyperplastic orbicularis oris (small white arrowheads) and postauricular muscle (large white arrowheads) on the left compared to the normal corresponding structures on the right.
An MRI and head and neck CT (Figs. 6 and 7) showed enlargement of the muscles of facial expression (as described above) on the right side. The muscles of mastication, including the medial pterygoid, lateral pterygoid, and temporalis muscles, were enlarged. The anterior and posterior digastric muscles were enlarged. The masseter muscle was not enlarged. The muscle signal and density were normal on all sequences. There was rightward deviation of the nasal bones and frontal process of maxilla toward the right. The right external auditory canal and tympanic cavity were smaller than on the left. A biopsy of muscle tissue has not been performed at this time. Patient 3 A 16-year-old female (Fig. 8) was referred to the Craniofacial Center for marked facial asymmetry on the left side. Past medical history was noncontributory. Family history was negative. On physical examination, gross asymmetry of the left face was noted. There was minimal malar ¯attening on the left. Her auricles were of normal contour and position. The patient exhibited a smaller nasal vestibule on the left than on the right. There was dimpling of the skin on the chin on the left side. Her chin was deviated to the left. The physical examination was remarkable for a right-sided giant hairy cell nevus on
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Fig. 4. Patient 1. Head MRI. Note the hyperplastic posterior digastric muscle on the left side (small white arrowhead).
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Fig. 5. Patient 2. AP photo. Note the narrow palpebral ®ssure on the right side and dimpling around the right oral comissure.
the back. The remainder of the physical exam was normal. An MRI and head and neck CT (Fig. 9) showed enlargement of the muscles of facial expression (as described above) on the left side. The posterior belly of the digastric muscle was enlarged, while the anterior belly was normal. The orbicularis oris and platysma were normal bilaterally. The medial and lateral pterygoid muscles showed enlargement, while the remainder of the muscles of mastication were normal. There was deviation of the cartilaginous nasal septum to the left. There was deviation of the nasal bones and frontal process of the maxilla to the left. Muscle signal and density were normal in all sequences. It was decided that a muscle biopsy might yield a more speci®c clinical diagnosis. The biopsy revealed normal appearing muscle on routine histology. DISCUSSION The vast majority of cases of hemifacial hyperplasia describe the involvement of all organ systems. Most of these cases describe clinical or radiological evidence of bone and muscle involvement, while only a few cases show histological evidence of hyperplasia of multiple organ systems. One case of hemifacial hyperplasia described a child with muscle, nerve, and lymphoid hyperplasia on one side of the face with airway compromise, but no hyperplasia of bone [Sculerti and
Fig. 6. Patient 2. Head CT. Note widening of the inferior orbital ®ssure (small arrows). Note the hyperplastic temporalis (large arrows), procerus (small white arrowheads), and obicularis oculi muscles (large arrowheads) on the right compared to the normal corresponding structures on the left.
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Fig. 7. Patient 2. Head CT. Note the normal posterior neck, sternocleidomastoid, and masseter muscles bilaterally. Note the hyperplastic platysma (large white arrow), zygomaticus (small gray arrows), medial and lateral pterygoid (small white arrows), and levator labii superiorus alequae nasi (large gray arrows) muscles on the right side compared to the normal corresponding structures on the left. Note the nasal tip deviation to the right.
Jacobs 1985]. In our review of the literature, only one work described hemifacial muscular hyperplasia without evidence of hyperplasia of other organ systems [Staffenberg et al., 1998]. Six patients were described with characteristics very similar to our three patients, summarized in Table III. All of our patients and the patients in Staffenberg et al. [1998] demonstrated unilateral hyperplasia of the muscles of facial expression and/or mastication with no evidence of hyperplasia of bone or other organ systems on the affected side. Changes in the facial skeleton of our patients and those in Staffenberg et al. [1998] showed either minimal hypoplastic changes or none at all. If bone remodeling does occur, it is likely secondary to the insertion of hyperplastic muscles on bone resulting in inappropriate contractile forces that cause bone remodeling. An example of this process is demonstrated on CT and MRI by the ipsilateral deviation of the frontal process of the maxilla and nasal bones toward the affected side in our patients. Our patients, as well as those of Staffenberg et al. [1998], exhibit dimpling of the skin at various sites on the face secondary to hyperplastic muscle in close proximity to the dermis pulling the skin away from the surface resulting in dimpling. In addition, malar
Fig. 8. Patient 3. AP photo. A: Note dimpling of the left oral comissure and left chin.
¯attening, auricular displacement, nasal deviation, chin deviation, narrowed palpebral ®ssure, and smaller nasal vestibule on the affected side were common facial characteristics in all of our patients and those of Staffenberg et al. [1998]. These deformations of facial structures are most likely secondary to hyperplastic facial muscles inserting into facial structures and causing inappropriate displacement. The severity of displacement varies according to the severity of the facial myohyperplasia, and may not be present at all if the patient exhibits a mild or early presentation of the disease. Four of six patients in Staffenberg et al. [1998] exhibited aberrant neck musculature on the affected side. It is interesting to note that the platysma in two of three of our patients was very hyperplastic and could easily be construed as an anomalous neck muscle. Considering the description of the patients with anomalous neck musculature in Staffenberg et al. [1998], this anomalous neck musculature may have actually been a hyperplastic platysma muscle. Facial nerve paresis is another common characteristic among our patients and those described by Staffenberg et al. [1998]. Facial nerve paresis may be explained by the inability of the nerve to function
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Fig. 9. Patient 3. Head CT. Note the deviation of the nose and septum to the left Note the hyperplastic zygomaticus (small white arrows) and levator labii superiorus alaquae nasi (large white arrows) muscles on the left compared to the normal corresponding structures on the right.
correctly with hyperplastic muscle ®bers, the inability of the muscle to contract properly to appropriate facial nerve stimulation, or primary cranial nerve dysfunction. It is interesting to note that none of our patients or those described in Staffenberg et al. [1998] exhibited
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trigeminal nerve dysfunction. In addition, abnormal muscle attachments can result in dis®guring facial expressions depending on the insertion and origin of these hyperplastic muscles, which may be mistaken for cranial nerve dysfunction. Our patients who have hyperplastic orbicularis oculi muscles demonstrate one example of this. These particular muscles seem to extend much farther posteriorly than normal on CT imaging, blending in with the pre-auricular muscles. Contraction of this facial muscle results in abnormal facial expressions. It is interesting to note the presence of multiple vascular malformations in our 2nd patient. None of the patients described by Staffenberg et al. [1998] or our other patients exhibited any obvious vascular malformation or abnormality. It is likely that our patient's lingual hemangioma and likely periocular lymphangioma are unrelated to the pathogenesis of hemifacial myohyperplasia. As the number of clinical reports of hemifacial myohyperplasia increases, this question may be answered more de®nitively. The etiology of hemifacial myohyperplasia is unknown. There are no changes in the surrounding fat of the hypertrophied muscle on CT or MRI that would indicate an in¯ammatory or neoplastic process. In addition, the muscle itself shows no abnormal signal indicating active in¯ammation or some other process accounting for muscle size. Various theories on the origin of hemihyperplasia have been described, including neurologic insults [Gorlin and Meskin, 1962], vascular and lymphatic disorders [Gorlin and Pindborg, 1976], endocrine abnormalities [Parker and Shalko, 1969], asymmetric cell division and deviation of the twinning process [Gesell, 1927], and asymmetric development of the neural fold with hyperplasia of neural crest cells [Pollock et al., 1985]. The muscles of the mastication and facial expression are derived from the 1st and 2nd branchial arches, respectively. In addition, the posterior belly of the digastric is derived from the 2nd branchial arch, while
TABLE III. Comparison of Characteristics of Hemifacial Myohyperplasia* Staffenberg et al. [1998]
This report
Characteristics
1
2
3
4
5
6
1
2
3
Sex Side Hyperplasia of muscle(s) of mastication (1st Arch) Hyperplasia of anterior belly of digastric (1st Arch) Hyperplasia of muscle(s) of facial expresion (2nd Arch) Hyperplasia of posterior belly of digastric (2nd Arch) Hypoplasia or dysplasia of facial skeleton Dimpling of skin Malar ¯attening Auricular displacement Nasal deviation Chin deviation Narrow palpebral ®ssure Small nasal vestibule Aberrant neck musculature Facial nerve paresis or paralysis
M L * * ÿ
M R * *
F L * * ÿ ÿ ÿ
M R * *
M L * * ÿ
M R ÿ * * ÿ ÿ ÿ ÿ ÿ ÿ
F L ÿ ÿ ÿ
F R ÿ ÿ
F L ÿ ÿ ÿ ÿ ÿ ÿ
*M, male; F, female; , present; ÿ, absent; *, unknown.
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the anterior portion is part of the 1st branchial arch. These 1st and 2nd branchial arches are innervated by cranial nerves V and VII, respectively. It is not currently known whether the nerves or muscles are determined ®rst in early development. It is known that cranial nerves V and VII innervate the branchial arches before they begin differentiation and migration [Fernandez Villoria, 1975]. Initially, the nerve seems to have no in¯uence on the early developmental stages of muscle, but in later development muscle differentiation and survival cannot continue without the facial nerve [May and Gasser, 2000]. Thus, it remains unclear what potential effect cranial innervation has on the development of hyperplasia. Hemifacial myohyperplasia is a disease process that occurs early in development during branchial arch formation. This is clearly shown by the differential involvement of the digastric muscle, which is innervated by the two separate cranial nerves, V and VII. In all three of our patients, the anterior belly of the digastric (cranial nerve V) was hyperplastic concurrently with the muscles of mastication (cranial nerve V). In addition, the posterior belly of the digastric (cranial nerve VII) was hyperplastic concurrently with the muscles of facial expression (cranial nerve VII). This shows the consistency of branchial arch involvement in hemifacial hyperplasia. However, hemifacial myohyperplasia does not always involve all of the muscles of the 1st or 2nd branchial arches. This would seem to indicate that hyperplasia might occur at a slightly later stage than the initial developmental stage, in which it would be more likely that all of the muscles of a particular branchial arch would be involved. Perhaps the degree of hyperplasia of the 1st and/or 2nd branchial arches is temporally related to muscle and nerve development. If the primary event that causes hemifacial myohyperplasia occurs later rather than earlier in facial development, perhaps fewer muscles have the potential to be involved because the window for involvement has passed. The theory would apply also to the differential amount of hyperplasia seen between the ®rst branchial arch musculature, which develops, ®rst and the second branchial arch musculature, which develops later. Another possibility for the differential involvement of hyperplasia in the muscles of facial expression and mastication was illustrated by Noden [1991]. He described how a single somitomere in the developing chick embryo can shift to a terminal site and give rise to a single muscle or a group of muscles. This might explain why in some of our patients certain muscles of facial expression and mastication are not involved in hyperplasia [Noden, 1991]. Further work needs to be done to help pinpoint the cause and pathogenesis of this disorder. In conclusion, our three cases and the six cases described by Staffenberg et al. [1998] warrant classi®cation as a distinct craniofacial syndrome. These patients have a collection of unique characteristics that distinguish them as a distinct entity separate from the previous attempts at classi®cation of ``partial'' or ``limited'' hemifacial hyperplasia by others. We suggest
the term hemifacial myohyperplasia. Classi®cation under this new syndrome would include the following characteristics, which will vary in presentation according to the severity of hyperplasia. (A) Primary de®nition: (i) Congenital hyperplasia of some or all of the muscles of the 1st (includes muscles of facial expression) and 2nd (includes muscles of mastication) branchial arches with no evidence of hyperplasia of bone or other organ systems on one side of the face. (B) Common facial characteristics: (i) Dimpling or wrinkling of the skin on the affected side. (ii) Narrowed palpebral ®ssure on the affected side. (iii) Nasal deviation towards the affected side. (iv) Smaller nasal vestibule on the affected side. (v) Auricular displacement inferiorly on the affected side. (vi) Malar ¯attening on the affected side. (vii) Chin deviation towards the affected side. (C) Other studied: (i) Radiographic studies when available will show unilateral enlargement of the muscles of facial expression and/or mastication with normal muscle signal. (ii) Histological analysis when available will demonstrate normal muscle. (D) Other possible ®ndings: (i) Secondary hypoplastic or dysplastic changes in the facial skeleton but no evidence of hyperplasia. (ii) Facial nerve paralysis of paresis, particularly of the marginal mandibular branch. Treatment for this condition at this time remains limited. In Staffenberg et al. [1998] various surgical procedures were performed to improve function and appearance in their patients, including otoplasty, muscle excision, canthopexy, and rhytidectomy. One of our patients is under consideration for botulinum toxin therapy to help reduce the dimpling effect of hyperplastic muscle and to help with dis®guring facial expressions upon contraction of certain muscles. Resection of muscle remains a possibility, although undergoing such a procedure would result in a high likelihood of injury to the facial nerve. Further work remains to be done on the cause of this disease and possible treatments for those who suffer from this dis®guring conditions. REFERENCES Beck CJ. 1836. Med Annalen von Puchelt. Chelius and Naegele 2. Cohen MM Jr. 1995. Perspectives on craniofacial asymmetry. IV. Hemiasymmetries. Int J Oral Maxillofac Surg 24:134±141. Fernandez Villoria JM. 1975. A study of the development of the orbicularis oris muscle. Plast Reconstr Surg 55:205±213. Gesell A. 1927. Hemihypertrophy and twinning: further study of nature of hemihypertrophy with report of new case. Am J Med Sci 173:542. Gorlin R, Meskin L. 1962. Congenital hemihypertrophy. J Paediatr 61:870±879.
Hemifacial Myohyperplasia Gorlin RJ, Pindborg JJ. 1976. Congenital hemihypertrophy. In: Jr MC, editors. Syndromes of the head and neck. New York: McGraw Hill Book Co. p 345±348. Kogon SL, Jarvis AM, Daley TD, Kane MF. 1984. Hemifacial hypertrophy affecting the maxillary dentition. Report of a case. Oral Surg Oral Med Oral Pathol 58:549±553. May M, Gasser RF. 2000. Embryonic development. In: May M, Schaitkin BM, editors. The facial nerve. New York: Thieme. p 1±17. Meckel J. 1822. Ueber die seitliche Asymmetrie in tierischen Korper. In: Anatomische physiologische Beobachtungen and untersuchungen. p 147. Noden DM. 1991. Cell movements and control of patterned tissue assembly during craniofacial development [comments]. J Craniofac Genet Dev Biol 11:192±213.
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Parker D, Shalko R. 1969. Congenital asymmetry. Report of ten cases with associated developmental abnormalities. Pediatric 44:584±589. Pollock RA, Newman MH, Burdi AR, Condit DP. 1985. Congenital hemifacial hyperplasia: an embryologic hypothesis and case report. Cleft Palate J 22:173±184. Rowe N. 1962. Hemifacial hypertrophy: review of literature and additional four cases. Oral Surg Oral Med Oral Pathol 15:572±587. Sculerati N, Jacobs JB. 1985. Congenital facial hemihypertrophy: report of a case with airway compromise. Head Neck Surg 8:124±128. Staffenberg DA, McCarthy JG, Hollier LH, Grayson BH, Verdi G. 1998. Hypertrophy and asymmetry of the facial muscles: a previously unrecognized association. Ann Plast Surg 40:533±537. Ward J, Lerner H. 1947. A review of the subject of congenital hemihypertrophy and a complete case report. J Pediatr 31:403±414.
