MANDIBULOFACIAL DYSOSTOSIS (TREACHER COLLINS SYNDROME): A CASE REPORT Dean L. Mittman, MD, and Orlando G. Rodman, MD Detroit, Michigan
Mandibulofacial dysostosis, also known as Treacher Collins syndrome, is a rare congenital anomaly that must be identified in infancy to prevent irrevocable developmental impairment. Information is sparse in the current medical literature concerning this rare syndrome. This article reports a case of Treacher Collins syndrome with the presence of a scarring alopecia and acne keloidalis nuchae, which are possibly coincidental symptoms, but have not been previously described clinically in this malady. (J Nati Med Assoc. 1992;84: 1051-1 054.) Key words * mandibulofacial dysostosis * Treacher Collins syndrome * autosomal dominant syndrome
Although the clinical features of mandibulofacial dysostosis were first reported by Thomson' in 1847, credit for its discovery is often given to E. Treacher Collins,2 who described two cases in 1900 and after whom the syndrome receives its eponym. In 1949, Franceschetti et al3 published a number of case reports detailing the constellation of findings one may see in this entity and renamed it mandibulofacial dysostosis. More than 250 cases of mandibulofacial dysostosis have been reported in the literature. The syndrome appears to be transmitted in an autosomal dominant manner with incomplete penetrance and variable expressivity. Classic findings in mandibulofacial dysostosis include antimongoloid slanting of the palpebral From the Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. Requests for reprints should be addressed to Dr Orlando G. Rodman, Vice-Chairman, Dept of Dermatology, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, Ml 48202. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 12
fissures, temporal lower eyelid coloboma, malar and mandibular hypoplasia, malformation of the auricle with atresia of the external auditory canals, and maldevelopment of the middle-ear ossicles and an associated conductive hearing loss. This article reports on a patient who, along with some of the classic features of mandibulofacial dysostosis, possesses the additional features of scarring alopecia and acne keloidalis nuchae.
CASE REPORT A 21-year-old black woman and her 18-month-old son (Figure 1) presented to the Henry Ford Hospital dermatology clinic. The woman was seeking treatment of nodular lesions along the posterior aspect of her scalp and neck. This woman was born with hypoplasia of the zygomatic arches, mandible, and external ear canals. There was total absence bilaterally of auricles except for the lobules. Throughout her lifetime, she had undergone multiple plastic surgical procedures to construct auricles and a reasonably normal appearing jaw. The patient had used a bone-conduction hearing aid since early childhood, enabling her to appreciate sound and master speech. Her family history was remarkable for a great grandfather with congenital anomalies similar to her own. Her parents, two brothers, and one sister were reportedly free of any congenital defects, and the patient's child, although bearing a striking resemblance to his mother, was healthy and normal. On physical examination, the patient's eyes were remarkable for a downward obliquity of the palpebral fissures, temporal notching of the lower lids (Figure 1B), and strabismus. Hypoplasia of the mandible was evident causing the upper dentition to appear protruding. Malar hypoplasia resulted in a "sunk-in" appearance temporally. The left parietal scalp possessed a
scarring, noninflammatory alopecia (Figure 2). Surgical 1051
-R5L~ ~ ~ . . .|
MANDIBULAR DYSOSTOSIS
-1
Figure 1. A) A 21 -year old patient with Treacher Collins syndrome and her 18-monthold son. Note the downward obliquity of pal pebral fissures with notching laterally of the mother's eyes (B) and the antimongoloid slanting of child's eyes (C).
cognia defects.
I~~~~~~~~~~ Figure 2. Scarring, noninflammatory alopecia.
construIction of aui-icles were appar-ent where the patient's own pinnae were absent (Figur-e 3). An earlobule was present bilaterally External ear- canals were atresic. Her posterior- nuchal reolon had m-ultiple small, firm, flesh-colored keloidal papules and nodules. The patient's child possessed an antimongoloid slant of his palpebral fissures and coloboma of the lateral lower lids (Figure IC) but was otherwise without any obvious
1052
Figure 3. Reconstructed auricles.
Histological examination of a 4-mm punch biopsy of the scalp in the region of the patient's alopecia revealed a significantly reduced number of follicles and sebaJOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 12
MANDIBULAR DYSOSTOSIS
TABLE 1. SYNDROMES AND CONDITIONS ASSOCIATED WITh CICATRICIAL ALOPECIA Aplasia cutis Lichen planopilaris Incontinentia pigmenti Scleroderma Focal dermal Cicatricial pemphigoid hypoplasia Sarcoidosis Epidermolysis bullosa Primary, metastatic Polyostotic fibrous carcinoma dysplasia Dissecting cellulitis Radiodermatitis, burns Pseudopelade Kerion, favus Folliculitis decalvans Lupus erythematosus
I~~~~~ 1Figure 4. Microscopic examination of the pa. tient's scarring alopecia showing a signifi. cantly reduced number of follicles and sebaceous glands (left) as well as the presence of fibrous cord formation in subcutaneous fat (right). ceous glands as well as the presence of fibrous cords at sites of destroyed hair follicles (Figure 4). These findings, together with absence of an inflammatory infiltrate, confirmed the diagnosis of late-stage scarring
alopecia. Our patient's acne keloidalis nuchae was treated with intralesional kenalog injections. As the scarring alopecia appeared noninflammatory, no treatment was deemed immediately necessary, and the patient was able to consider the option of scalp reduction for cosmesis. Genetic counseling was provided to the patient, and her child was referred to otolaryngology for special testing to rule out any middle ear involvement.
DISCUSSION The characteristic facies in the Treacher Collins syndrome suggests a mechanism of malformation that operates early in embryogenesis, acting uniformly on parts that are derived from neural crest cells. The neural crest has been shown to make a major contribution to those structures developing in the first and second branchial arches that form the skeleton and connective tissues of the face. Between the arches are the branchial clefts. The first branchial arch splits into maxillary and mandibular processes. The maxilla, upper lip, and cheek develop from the maxillary arch as do the inferior portion of the helix and the tragus of the ear. The mandibular process produces the mandible, lower lip, malleus, and incus of the middle ear. The external auditory canal, the tympanic membrane and the Eustachian apparatus develop from within the intervenJOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 12
TABLE 2. SYNDROMES ASSOCIATED WITH DEAFNESS Treacher Collins Pendred's syndrome syndrome Goldenhar's syndrome Waardenburg's Crouzon's syndrome syndrome Leopard syndrome Apert's syndrome Alport's syndrome Down syndrome Fanconi's syndrome Orofaciodigital Torch syndrome syndrome Fetal alcohol syndrome Hidrotic ectodermal dysplasia
ing branchial cleft. Differentiation of all these structures in the first and second branchial arches is usually complete by the seventh to eighth week of gestation. Mandibulofacial dysostosis represents a characteristic pattern of craniofacial malformation distinct from other first and second branchial arch anomalies.4 To date, the Treacher Collins syndrome is an entity discussed primarily in the ophthalmologic, otolaryngologic, and plastic surgical literature. There has essentially been a void in the dermatologic literature with regard to this topic. Our patient presented for treatment of acne keloidalis nuchae and scarring alopecia, both common ailments. However, as these symptoms have not previously been described in conjunction with the Treacher Collins syndrome, we felt this case to be noteworthy. Tables 1 and 2 list many of the syndromes associated with alopecia and deafness, respectively. Because the ramifications of this malady is unrecognized, early diagnosis of the syndrome of mandibulofacial dysostosis is crucial. As the great majority of these patients are of normal intelligence, early recognition of deafness and its correction with hearing aids or surgery, when possible, is of great importance for development. The development of speech and language skills depends on the child's ability to hear during the first 3 years of 1053
MANDIBULAR DYSOSTOSIS
life. In 1978, Ilaides5 reported a case of Treacher Collins syndrome in which the patient had normal external ear canal and auricle development but experienced significant hearing loss. The hearing loss was documented audiometrically and was identified surgically to be secondary to maldevelopment of the stapes. This case prompted us to obtain otoscopic and audiometric analysis of our patient's child even though he was free of any external ear canal defect. Less pressing but nonetheless extremely important are the psychological stresses for the affected individual and family. It may be possible to avoid some degree of behavioral and psychological trauma if plastic surgery is performed early. Rogers6 describes ear reconstruction, malar augmentation, rhinoplasty, and chin advancement procedures for treating mandibulofacial dysostosis that may be performed at an early stage. Our patient expressed satisfaction with her plastic surgery and appeared to be quite well adjusted. Treacher Collins syndrome is an example of an autosomal dominant syndrome with incomplete penetrance and variable expressivity.7-'0 An affected parent of either sex will transmit the defect to 50% of his or her offspring in accordance with mendelian laws of genetics. This emphasizes the importance of genetic counseling to affected individuals. Many, as did our patient, will choose to procreate so it is our responsibil-
1054
ity as physicians to recognize this disorder, to be aware of both the classic and more subtle manifestations of this syndrome, and to provide close follow-up and appropriate therapy and counseling. Literature Cited 1. Thomson A. Notice of several cases of malformation of the external ear, together with experiments on the state of hearing in such persons. Monthly Journal of Medicine and Science. 1846;7:420-424. 2. Collins TE. Case with symmetrical congenital notches in the outer part of each lower lid and defective development of the malar bones. Transactions of the Ophthalmological Society of the United Kingdom.1900;20:190-193. 3. Franceschetti A, Klein D. The mandibulofacial dysostosis, a new hereditary syndrome. Acta Ophthalmol (Copenh). 1949;27:144-146. 4. Poseillo D. The pathogenesis of the Treacher Collins syndrome. Br J Oral Surg. 1975;1 3:1-26. 5. Iliades C. An atypical case of Treacher Collins syndrome. Ear Nose Throat J. 1978;57:486-489. 6. Rogers BO. The surgical treatment of mandibulofacial dysostosis. Clin Plastic Surg. 1976;3:653-666. 7. Phelps PD, Poswillo D, Lloyd G. The ear deformities in mandibulofacial dysostosis. Clin Otolaryngol. 1981 ;6:15-28. 8. Fazen LE, Elmor J, Nadler HL. Mandibulofacial dysosto-
sis. Am J Dis Child. 1967;1 13:405-407. 9. Marsh JL. The skeletal anatomy of mandibulofacial dysostosis. Plastic Reconstr Surg. 1986;78:460-468. 10. English GM. Otolaryngology. Philadelphia, Pa: JB Lippincott Co; 1988.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 12
Mandibulofacial dysostosis, also known as Treacher Collins syndrome, is a rare congenital anomaly that must be identified in infancy to prevent irrevocable developmental impairment. Information is sparse in the current medical literature concerning this rare syndrome. This article reports a case of Treacher Collins syndrome with the presence of a scarring alopecia and acne keloidalis nuchae, which are possibly coincidental symptoms, but have not been previously described clinically in this malady. (J Nati Med Assoc. 1992;84: 1051-1 054.) Key words * mandibulofacial dysostosis * Treacher Collins syndrome * autosomal dominant syndrome
Although the clinical features of mandibulofacial dysostosis were first reported by Thomson' in 1847, credit for its discovery is often given to E. Treacher Collins,2 who described two cases in 1900 and after whom the syndrome receives its eponym. In 1949, Franceschetti et al3 published a number of case reports detailing the constellation of findings one may see in this entity and renamed it mandibulofacial dysostosis. More than 250 cases of mandibulofacial dysostosis have been reported in the literature. The syndrome appears to be transmitted in an autosomal dominant manner with incomplete penetrance and variable expressivity. Classic findings in mandibulofacial dysostosis include antimongoloid slanting of the palpebral From the Department of Dermatology, Henry Ford Hospital, Detroit, Michigan. Requests for reprints should be addressed to Dr Orlando G. Rodman, Vice-Chairman, Dept of Dermatology, Henry Ford Hospital, 2799 W Grand Blvd, Detroit, Ml 48202. JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 12
fissures, temporal lower eyelid coloboma, malar and mandibular hypoplasia, malformation of the auricle with atresia of the external auditory canals, and maldevelopment of the middle-ear ossicles and an associated conductive hearing loss. This article reports on a patient who, along with some of the classic features of mandibulofacial dysostosis, possesses the additional features of scarring alopecia and acne keloidalis nuchae.
CASE REPORT A 21-year-old black woman and her 18-month-old son (Figure 1) presented to the Henry Ford Hospital dermatology clinic. The woman was seeking treatment of nodular lesions along the posterior aspect of her scalp and neck. This woman was born with hypoplasia of the zygomatic arches, mandible, and external ear canals. There was total absence bilaterally of auricles except for the lobules. Throughout her lifetime, she had undergone multiple plastic surgical procedures to construct auricles and a reasonably normal appearing jaw. The patient had used a bone-conduction hearing aid since early childhood, enabling her to appreciate sound and master speech. Her family history was remarkable for a great grandfather with congenital anomalies similar to her own. Her parents, two brothers, and one sister were reportedly free of any congenital defects, and the patient's child, although bearing a striking resemblance to his mother, was healthy and normal. On physical examination, the patient's eyes were remarkable for a downward obliquity of the palpebral fissures, temporal notching of the lower lids (Figure 1B), and strabismus. Hypoplasia of the mandible was evident causing the upper dentition to appear protruding. Malar hypoplasia resulted in a "sunk-in" appearance temporally. The left parietal scalp possessed a
scarring, noninflammatory alopecia (Figure 2). Surgical 1051
-R5L~ ~ ~ . . .|
MANDIBULAR DYSOSTOSIS
-1
Figure 1. A) A 21 -year old patient with Treacher Collins syndrome and her 18-monthold son. Note the downward obliquity of pal pebral fissures with notching laterally of the mother's eyes (B) and the antimongoloid slanting of child's eyes (C).
cognia defects.
I~~~~~~~~~~ Figure 2. Scarring, noninflammatory alopecia.
construIction of aui-icles were appar-ent where the patient's own pinnae were absent (Figur-e 3). An earlobule was present bilaterally External ear- canals were atresic. Her posterior- nuchal reolon had m-ultiple small, firm, flesh-colored keloidal papules and nodules. The patient's child possessed an antimongoloid slant of his palpebral fissures and coloboma of the lateral lower lids (Figure IC) but was otherwise without any obvious
1052
Figure 3. Reconstructed auricles.
Histological examination of a 4-mm punch biopsy of the scalp in the region of the patient's alopecia revealed a significantly reduced number of follicles and sebaJOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 12
MANDIBULAR DYSOSTOSIS
TABLE 1. SYNDROMES AND CONDITIONS ASSOCIATED WITh CICATRICIAL ALOPECIA Aplasia cutis Lichen planopilaris Incontinentia pigmenti Scleroderma Focal dermal Cicatricial pemphigoid hypoplasia Sarcoidosis Epidermolysis bullosa Primary, metastatic Polyostotic fibrous carcinoma dysplasia Dissecting cellulitis Radiodermatitis, burns Pseudopelade Kerion, favus Folliculitis decalvans Lupus erythematosus
I~~~~~ 1Figure 4. Microscopic examination of the pa. tient's scarring alopecia showing a signifi. cantly reduced number of follicles and sebaceous glands (left) as well as the presence of fibrous cord formation in subcutaneous fat (right). ceous glands as well as the presence of fibrous cords at sites of destroyed hair follicles (Figure 4). These findings, together with absence of an inflammatory infiltrate, confirmed the diagnosis of late-stage scarring
alopecia. Our patient's acne keloidalis nuchae was treated with intralesional kenalog injections. As the scarring alopecia appeared noninflammatory, no treatment was deemed immediately necessary, and the patient was able to consider the option of scalp reduction for cosmesis. Genetic counseling was provided to the patient, and her child was referred to otolaryngology for special testing to rule out any middle ear involvement.
DISCUSSION The characteristic facies in the Treacher Collins syndrome suggests a mechanism of malformation that operates early in embryogenesis, acting uniformly on parts that are derived from neural crest cells. The neural crest has been shown to make a major contribution to those structures developing in the first and second branchial arches that form the skeleton and connective tissues of the face. Between the arches are the branchial clefts. The first branchial arch splits into maxillary and mandibular processes. The maxilla, upper lip, and cheek develop from the maxillary arch as do the inferior portion of the helix and the tragus of the ear. The mandibular process produces the mandible, lower lip, malleus, and incus of the middle ear. The external auditory canal, the tympanic membrane and the Eustachian apparatus develop from within the intervenJOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 12
TABLE 2. SYNDROMES ASSOCIATED WITH DEAFNESS Treacher Collins Pendred's syndrome syndrome Goldenhar's syndrome Waardenburg's Crouzon's syndrome syndrome Leopard syndrome Apert's syndrome Alport's syndrome Down syndrome Fanconi's syndrome Orofaciodigital Torch syndrome syndrome Fetal alcohol syndrome Hidrotic ectodermal dysplasia
ing branchial cleft. Differentiation of all these structures in the first and second branchial arches is usually complete by the seventh to eighth week of gestation. Mandibulofacial dysostosis represents a characteristic pattern of craniofacial malformation distinct from other first and second branchial arch anomalies.4 To date, the Treacher Collins syndrome is an entity discussed primarily in the ophthalmologic, otolaryngologic, and plastic surgical literature. There has essentially been a void in the dermatologic literature with regard to this topic. Our patient presented for treatment of acne keloidalis nuchae and scarring alopecia, both common ailments. However, as these symptoms have not previously been described in conjunction with the Treacher Collins syndrome, we felt this case to be noteworthy. Tables 1 and 2 list many of the syndromes associated with alopecia and deafness, respectively. Because the ramifications of this malady is unrecognized, early diagnosis of the syndrome of mandibulofacial dysostosis is crucial. As the great majority of these patients are of normal intelligence, early recognition of deafness and its correction with hearing aids or surgery, when possible, is of great importance for development. The development of speech and language skills depends on the child's ability to hear during the first 3 years of 1053
MANDIBULAR DYSOSTOSIS
life. In 1978, Ilaides5 reported a case of Treacher Collins syndrome in which the patient had normal external ear canal and auricle development but experienced significant hearing loss. The hearing loss was documented audiometrically and was identified surgically to be secondary to maldevelopment of the stapes. This case prompted us to obtain otoscopic and audiometric analysis of our patient's child even though he was free of any external ear canal defect. Less pressing but nonetheless extremely important are the psychological stresses for the affected individual and family. It may be possible to avoid some degree of behavioral and psychological trauma if plastic surgery is performed early. Rogers6 describes ear reconstruction, malar augmentation, rhinoplasty, and chin advancement procedures for treating mandibulofacial dysostosis that may be performed at an early stage. Our patient expressed satisfaction with her plastic surgery and appeared to be quite well adjusted. Treacher Collins syndrome is an example of an autosomal dominant syndrome with incomplete penetrance and variable expressivity.7-'0 An affected parent of either sex will transmit the defect to 50% of his or her offspring in accordance with mendelian laws of genetics. This emphasizes the importance of genetic counseling to affected individuals. Many, as did our patient, will choose to procreate so it is our responsibil-
1054
ity as physicians to recognize this disorder, to be aware of both the classic and more subtle manifestations of this syndrome, and to provide close follow-up and appropriate therapy and counseling. Literature Cited 1. Thomson A. Notice of several cases of malformation of the external ear, together with experiments on the state of hearing in such persons. Monthly Journal of Medicine and Science. 1846;7:420-424. 2. Collins TE. Case with symmetrical congenital notches in the outer part of each lower lid and defective development of the malar bones. Transactions of the Ophthalmological Society of the United Kingdom.1900;20:190-193. 3. Franceschetti A, Klein D. The mandibulofacial dysostosis, a new hereditary syndrome. Acta Ophthalmol (Copenh). 1949;27:144-146. 4. Poseillo D. The pathogenesis of the Treacher Collins syndrome. Br J Oral Surg. 1975;1 3:1-26. 5. Iliades C. An atypical case of Treacher Collins syndrome. Ear Nose Throat J. 1978;57:486-489. 6. Rogers BO. The surgical treatment of mandibulofacial dysostosis. Clin Plastic Surg. 1976;3:653-666. 7. Phelps PD, Poswillo D, Lloyd G. The ear deformities in mandibulofacial dysostosis. Clin Otolaryngol. 1981 ;6:15-28. 8. Fazen LE, Elmor J, Nadler HL. Mandibulofacial dysosto-
sis. Am J Dis Child. 1967;1 13:405-407. 9. Marsh JL. The skeletal anatomy of mandibulofacial dysostosis. Plastic Reconstr Surg. 1986;78:460-468. 10. English GM. Otolaryngology. Philadelphia, Pa: JB Lippincott Co; 1988.
JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 84, NO. 12
