Aplasia of the first and second branchial arches By G. B. LECKIE (Nottingham) THE rare lethal sydrome of microstomia, aglossia, angnathia and synotia is the most severe form of the so-called first branchial arch anomalies. A baby with this combination of malformations is described and compared to the current concepts of embryology and pathogenesis of the first and second branchial arch syndrome. History
A 27-year-old primigravida with a family history of mongolism was referred at twenty-eight weeks gestation with a clinical diagnosis of severe hydramnios. The patient was so distended by the thirty-second week of gestation that sh e required amniocentesis. Four litres of liquor amnii were slowly withdrawn. A plain X-ray of the abdomen (see Fig. 1) was also taken. Ten days later premature onset of labour occurred with spontaneous rupture of the membranes. After a short three hour labour a fresh stillborn female monster was delivered by the breech. Postmortem report External
Appearances
A 1550 gms. female infant with normal external genitalia, widely spaced nipples and facial abnormalities consequent upon failure of the development of the mandible. The cranium, eyes and nose were normal. No proper upper lip was present. The oral cavity communicated with the outside by a tiny central stoma. As a result of the absence of the mandible, the ears were situated low down below the small oral stoma and lay very close to the midline obliquely. (Fig. 2). The pinnae were located on the upper anterior cervical region near the midline of the neck (synotial). A fistulous tract was thought to be present between the hypopharynx and the cleft of the external auditory canals (however, on dissection this proved not to be). Internal appearances
The roof of the buccal cavity was formed by the very high arched palate. The alveolar arches of the maxilla were very broad and elongated and almost met in the middle, leaving a central narrow slit through which a fine probe could be passed to the high-arched palate. From the soft palate hung a long thin uvula. 1263
G. B. Leckie The buccal cavity was small, its floor being lined by mucosa and formed by unidentified muscle and connective tissue. There was a mucosal covered membrane forming the posterior wall of the buccal cavity at the level of the soft palate, just past the uvula, with a high pinhole communication with the pharyngeal cavity (Fig. 3.). There was no tongue in the buccal cavity.
FIG.
1
The nasal cavity and sinuses were normal except that the nasal cavity communicated with the pharyngeal cavity through a very small ostium. The pharyngeal cavity was isolated from the buccal and nasal cavities except for these pinhole communications. The upper end of the oesophagus and the larynx open into the lower pharynx normally. The epiglottis was normal. Immediately above the epiglottis was a very small tongue attached to the anterior wall of the pharynx over all its base; the tip was not free. Thyroid and parathyroids were normal as were the thyroid cartilages. The heart and lungs were normal except that the lungs were uninflated. 1264
Aplasia of the first and second branchial arches The thymus was large and weighed 17 gms. The kidneys, adrenals, ureters and internal genitalia were normal. There were no limb or other skeletal abnormalities.
FIG.
2
G. B. Leckie Introduction
Malformation of the derivatives of the first and second branchial arches in man has been recorded at regular intervals over the past centuries. (Thompson 1845). Only in very recent years has there been any attempt at classification of this syndrome and its possible embryological foundation. (Ruben 1967, McKenzie 1968). In its broadest sense, the first and second branchial arch syndrome includes an array of defects involving not only those derivatives of the first and second arches and cleft, but also the primordia of the temporal bone. The defects are usually, but not invariably, unilateral; there is frequently a considerable difference in the expressions of the syndrome between the two sides in bilateral cases. The incidence of this characteristic syndrome is about 1 per 4,000 births However, during the thalidomide disaster, there was a virtual epidemic of otomandibular defects, (Kleinsasser, 1964; Smithells 1963) often in association with limb deformities. The most severe and extremely rare form of first and second arch malformation is found in otocephalic monsters. The syndrome of otocephalus varies, but usually consists of severe mandibular hypoplasia or agnathia, ventromedial displacement of the external ear structures (synotia), microstomia and severe hypoplasia or absence of the tongue (aglossia). Associated anomalies often include horseshoe kidney, valvular heart disease pharyngeal stenosis (or atresia), situs inversus, cyclops, anomalies of the extremities (e.g. club foot) and central nervous system deformities. (Gorlin 1964). This paper is on such a monster and it is an attempt to clarify the present position on this rare syndrome. Embryology
During the sixth week of fetal life, the onset of external auricular develment is marked by the appearance of six hillocks around the dorsal end of the first branchial groove. The hillocks fuse into two folds of the developing pinna later the same week. The mandibular arch provides the anlage for the anterior fold and the hyoid arch contributes to the posterior fold. Further fusion of the two folds then occurs at the upper end of the first branchial groove. According to the concept of His, the first three hillocks (mandibular arch) give rise to the tragus, crus of helix and the major portion of the helix, while the last three hillocks (hyoid) give rise to the anthelix, antitragus and the lobule and lower helix. Many authors, (Rogers 1968; Woods-Jones 1967), challenged this concept and presented convincing arguments to support the theory that the tragus was the only major portion of the auricle arising from the mandibular arch anlage. This is supported by the distribution of preauricular fistulae and appendages, the configuration of the external ear in 1266
Aplasia of the first and second branchial arches cases of arrested development of the mandibular arch. Development of the pinna is apparently not entirely dependent upon the mutual forces directting maturation of the ventral portions of the first and second branchial arch derivatives. This fact is confirmed by this case report as well as others. (Black 1973). Deformities of the pinna in this report were minimal, despite the severe first arch maldevelopment. All cartilagenous structures of the external ear were well developed except the tragus and anteriorly deficient external auditory canal. (Fig. 4).
FIG.
4
The external auditory canal develops from the dorsal portion of the first branchial groove, whereas the ventral portion disappears. The middle portion of the first branchial groove gives rise to the cavum conchae, the upper part becomes the conchae and the lower part becomes the lower part of the intertragal notch. The external auricular blastema lies anteromedially at first during development, but is then displaced dorsolaterally as the mandible and face develop during the second month. Arrest of the ventral first arch growth must therefore occur before the eighth week. (Pearson 1967). The findings in this report are consistent with this developmental sequence of the external ear anatomy. The more accepted concept of maxillary development from the mandibular arch primordia is disputed by some authors, (Keen 1955; Horstaclius 1950; Altman 1957), who cite that the primordia for the maxillary T267
G. B. Leckie processes are derived from the mesenchyme which migrates from the ventral neural crest to form portions of the skull base and maxilla. This report shows there to be maxillary development without a mandible, so so supporting the latter theory. The midface structures were altered to some extent in this case report as they are in most otocephalic deformities. The presence of a cleftpalate with absence of a tongue does not support the concept that ventrocaudal displacement of the tongue from between the palatal shelves permits palatal shelf closure and horizontalization. (Wragg 1970). The tongue is both a pharyngeal and branchomeric derivative. The oral portion arises from the first (mandibular) arch; the pharyngeal portion comes from the second (hyoid) blastema. In addition, the tongue must receive contributions from the third and fourth arches (Arey 1965). The tuberculum impar first appears on the pharyngeal floor between the first pair of pharyngeal pouches, at about the fourth week of development. This midline structure fuses with paired lateral lingual swellings from the first branchial arches to form the tongue body. The small rudimentary tongue in this baby found in the anterior pharyngeal wall probably represents the hypobranchial eminence of the third and fourth arches. Although there have been many reports of otomandibular dysostosis, little attempt has been made to explain the distribution of the maldevelopments on a sound embryological basis. The findings in this report support the contention that malformations seen in otocephalus result from arrested development, primarily of the ventral mandibular and hyoid arch derivatives, whereas the dorsal, more direct, derivatives of Meckel and Reichert cartilagenous bars appear to be much less affected. Pathogenesis
The aetiology of the first and second arch syndrome has long been sought. Keith (1909) and Braithwaite (1949) concluded that the effects resulted from intrauterine facial necrosis due to failure or partial failure of the development of the stapedial artery. The stapedial artery is a temporary structure in that it appears on the thirty-third day of embryonic life and supplies the primordia of the first and second branchial arches until it is replaced by the finite external carotid arterial system which occurs at about the fortieth day of embryonic life. Poswillo and co-workers (1972) produced a series of otomandibular malformations similar to those found in man in a Marmoset using thalidomide as their teratogenic agent at a similar period of embryogenesis. Poswillo (1973) then went on to show that the causal mechanism is one of embryonic hematoma formation, the haemorrhage arising from the anas1268
Aplasia of the first and second branchial arches tomosis which precedes the formation of the stapedial arterial stem. The variable of the syndrome was shown to be related to the variations in form and duration of the hematoma in his animal experiments. Summary
This case report of an otocephalic monster gave the opportunity to study severe orofacial anomalies with a view to clarifying the present position in regard to the so-called first and second arch syndrome. Finding the causal mechanism of this syndrome will eventually lead to prevention and, it is hoped, eradication of this syndrome. Acknowledgements
I would like to thank Mr. R. T. Sears, Consultant Obstetrician and Gynaecologist to The Women's Hospital, Nottingham and Prof. D. E. Poswillo of The Royal College of Surgeons of England for advice and encouragement in presenting this report. REFERENCES ALTMAN, F. (1957) Archives of Otolaryngology, 66, 7, 25. AREY, L. B. (1965) Development Anatomy. W. B. Saunders Co. BLACK, L. B., MYERS, E. N., and RORKE, L. B. (1973) Archives of Otolaryngology,
98, 123-8. BRAITHWAITE, F. (1949) British Journal of Plastic Surgery, 2, 38. GORLIN, R. J., and PINDBORG, J. J. (1964) Syndromes of the Head and Neck. McGraw Book Co. Inc., 368-9. HORSTACLIUS, S. (1950) The Neural Crest. Oxford University Press, 7, 35. KEEN, J. A. (1955) South African Journal of Laboratory Clinical Medicine, 1, 197-202. KEITH, A. (1909) British Medical Journal, 2483. KLEINASSER, O. (1964) German Journal of Laryngology and Otolaryngology, 43, 344. MCKENZIE, J. (1958) Archives of the Diseases of Children, 33, 477. PEARSON, A. A. (1967) Development of the Ear. American Academy of Ophthalmology and Otolaryngology. POSWILLO, D. E., and SOPHER, D. (1972) Nature, 269, 460.
(1973) British Journal of Oral Surgery, 3, 303, 327. ROGERS, B. O. (1968) Craniofacial Anomalies. J. B. Lippincott Co., Philadelphia. RUBEN, A. (1967) Handbook of Congenital Malformation. W. B. Saunders Co., Philadelphia. SMITHELLS, R. W., and LECK, I. (1963) Lancet, 1, 1095.
THOMPSON, A. (1845) Proceedings of the Royal Society, Edinburgh, 1, 433. WRAGG, L. E. (1970) Archives of Oral Biology, 15, 705-19. WOOD-JONES, F., and I-CHAUN, W. (1934) Journal of Anatomy, 68, 525-33. The Nottingham Hospital for Women Peel Street Nottingham NGi 4GP
1269
A 27-year-old primigravida with a family history of mongolism was referred at twenty-eight weeks gestation with a clinical diagnosis of severe hydramnios. The patient was so distended by the thirty-second week of gestation that sh e required amniocentesis. Four litres of liquor amnii were slowly withdrawn. A plain X-ray of the abdomen (see Fig. 1) was also taken. Ten days later premature onset of labour occurred with spontaneous rupture of the membranes. After a short three hour labour a fresh stillborn female monster was delivered by the breech. Postmortem report External
Appearances
A 1550 gms. female infant with normal external genitalia, widely spaced nipples and facial abnormalities consequent upon failure of the development of the mandible. The cranium, eyes and nose were normal. No proper upper lip was present. The oral cavity communicated with the outside by a tiny central stoma. As a result of the absence of the mandible, the ears were situated low down below the small oral stoma and lay very close to the midline obliquely. (Fig. 2). The pinnae were located on the upper anterior cervical region near the midline of the neck (synotial). A fistulous tract was thought to be present between the hypopharynx and the cleft of the external auditory canals (however, on dissection this proved not to be). Internal appearances
The roof of the buccal cavity was formed by the very high arched palate. The alveolar arches of the maxilla were very broad and elongated and almost met in the middle, leaving a central narrow slit through which a fine probe could be passed to the high-arched palate. From the soft palate hung a long thin uvula. 1263
G. B. Leckie The buccal cavity was small, its floor being lined by mucosa and formed by unidentified muscle and connective tissue. There was a mucosal covered membrane forming the posterior wall of the buccal cavity at the level of the soft palate, just past the uvula, with a high pinhole communication with the pharyngeal cavity (Fig. 3.). There was no tongue in the buccal cavity.
FIG.
1
The nasal cavity and sinuses were normal except that the nasal cavity communicated with the pharyngeal cavity through a very small ostium. The pharyngeal cavity was isolated from the buccal and nasal cavities except for these pinhole communications. The upper end of the oesophagus and the larynx open into the lower pharynx normally. The epiglottis was normal. Immediately above the epiglottis was a very small tongue attached to the anterior wall of the pharynx over all its base; the tip was not free. Thyroid and parathyroids were normal as were the thyroid cartilages. The heart and lungs were normal except that the lungs were uninflated. 1264
Aplasia of the first and second branchial arches The thymus was large and weighed 17 gms. The kidneys, adrenals, ureters and internal genitalia were normal. There were no limb or other skeletal abnormalities.
FIG.
2
G. B. Leckie Introduction
Malformation of the derivatives of the first and second branchial arches in man has been recorded at regular intervals over the past centuries. (Thompson 1845). Only in very recent years has there been any attempt at classification of this syndrome and its possible embryological foundation. (Ruben 1967, McKenzie 1968). In its broadest sense, the first and second branchial arch syndrome includes an array of defects involving not only those derivatives of the first and second arches and cleft, but also the primordia of the temporal bone. The defects are usually, but not invariably, unilateral; there is frequently a considerable difference in the expressions of the syndrome between the two sides in bilateral cases. The incidence of this characteristic syndrome is about 1 per 4,000 births However, during the thalidomide disaster, there was a virtual epidemic of otomandibular defects, (Kleinsasser, 1964; Smithells 1963) often in association with limb deformities. The most severe and extremely rare form of first and second arch malformation is found in otocephalic monsters. The syndrome of otocephalus varies, but usually consists of severe mandibular hypoplasia or agnathia, ventromedial displacement of the external ear structures (synotia), microstomia and severe hypoplasia or absence of the tongue (aglossia). Associated anomalies often include horseshoe kidney, valvular heart disease pharyngeal stenosis (or atresia), situs inversus, cyclops, anomalies of the extremities (e.g. club foot) and central nervous system deformities. (Gorlin 1964). This paper is on such a monster and it is an attempt to clarify the present position on this rare syndrome. Embryology
During the sixth week of fetal life, the onset of external auricular develment is marked by the appearance of six hillocks around the dorsal end of the first branchial groove. The hillocks fuse into two folds of the developing pinna later the same week. The mandibular arch provides the anlage for the anterior fold and the hyoid arch contributes to the posterior fold. Further fusion of the two folds then occurs at the upper end of the first branchial groove. According to the concept of His, the first three hillocks (mandibular arch) give rise to the tragus, crus of helix and the major portion of the helix, while the last three hillocks (hyoid) give rise to the anthelix, antitragus and the lobule and lower helix. Many authors, (Rogers 1968; Woods-Jones 1967), challenged this concept and presented convincing arguments to support the theory that the tragus was the only major portion of the auricle arising from the mandibular arch anlage. This is supported by the distribution of preauricular fistulae and appendages, the configuration of the external ear in 1266
Aplasia of the first and second branchial arches cases of arrested development of the mandibular arch. Development of the pinna is apparently not entirely dependent upon the mutual forces directting maturation of the ventral portions of the first and second branchial arch derivatives. This fact is confirmed by this case report as well as others. (Black 1973). Deformities of the pinna in this report were minimal, despite the severe first arch maldevelopment. All cartilagenous structures of the external ear were well developed except the tragus and anteriorly deficient external auditory canal. (Fig. 4).
FIG.
4
The external auditory canal develops from the dorsal portion of the first branchial groove, whereas the ventral portion disappears. The middle portion of the first branchial groove gives rise to the cavum conchae, the upper part becomes the conchae and the lower part becomes the lower part of the intertragal notch. The external auricular blastema lies anteromedially at first during development, but is then displaced dorsolaterally as the mandible and face develop during the second month. Arrest of the ventral first arch growth must therefore occur before the eighth week. (Pearson 1967). The findings in this report are consistent with this developmental sequence of the external ear anatomy. The more accepted concept of maxillary development from the mandibular arch primordia is disputed by some authors, (Keen 1955; Horstaclius 1950; Altman 1957), who cite that the primordia for the maxillary T267
G. B. Leckie processes are derived from the mesenchyme which migrates from the ventral neural crest to form portions of the skull base and maxilla. This report shows there to be maxillary development without a mandible, so so supporting the latter theory. The midface structures were altered to some extent in this case report as they are in most otocephalic deformities. The presence of a cleftpalate with absence of a tongue does not support the concept that ventrocaudal displacement of the tongue from between the palatal shelves permits palatal shelf closure and horizontalization. (Wragg 1970). The tongue is both a pharyngeal and branchomeric derivative. The oral portion arises from the first (mandibular) arch; the pharyngeal portion comes from the second (hyoid) blastema. In addition, the tongue must receive contributions from the third and fourth arches (Arey 1965). The tuberculum impar first appears on the pharyngeal floor between the first pair of pharyngeal pouches, at about the fourth week of development. This midline structure fuses with paired lateral lingual swellings from the first branchial arches to form the tongue body. The small rudimentary tongue in this baby found in the anterior pharyngeal wall probably represents the hypobranchial eminence of the third and fourth arches. Although there have been many reports of otomandibular dysostosis, little attempt has been made to explain the distribution of the maldevelopments on a sound embryological basis. The findings in this report support the contention that malformations seen in otocephalus result from arrested development, primarily of the ventral mandibular and hyoid arch derivatives, whereas the dorsal, more direct, derivatives of Meckel and Reichert cartilagenous bars appear to be much less affected. Pathogenesis
The aetiology of the first and second arch syndrome has long been sought. Keith (1909) and Braithwaite (1949) concluded that the effects resulted from intrauterine facial necrosis due to failure or partial failure of the development of the stapedial artery. The stapedial artery is a temporary structure in that it appears on the thirty-third day of embryonic life and supplies the primordia of the first and second branchial arches until it is replaced by the finite external carotid arterial system which occurs at about the fortieth day of embryonic life. Poswillo and co-workers (1972) produced a series of otomandibular malformations similar to those found in man in a Marmoset using thalidomide as their teratogenic agent at a similar period of embryogenesis. Poswillo (1973) then went on to show that the causal mechanism is one of embryonic hematoma formation, the haemorrhage arising from the anas1268
Aplasia of the first and second branchial arches tomosis which precedes the formation of the stapedial arterial stem. The variable of the syndrome was shown to be related to the variations in form and duration of the hematoma in his animal experiments. Summary
This case report of an otocephalic monster gave the opportunity to study severe orofacial anomalies with a view to clarifying the present position in regard to the so-called first and second arch syndrome. Finding the causal mechanism of this syndrome will eventually lead to prevention and, it is hoped, eradication of this syndrome. Acknowledgements
I would like to thank Mr. R. T. Sears, Consultant Obstetrician and Gynaecologist to The Women's Hospital, Nottingham and Prof. D. E. Poswillo of The Royal College of Surgeons of England for advice and encouragement in presenting this report. REFERENCES ALTMAN, F. (1957) Archives of Otolaryngology, 66, 7, 25. AREY, L. B. (1965) Development Anatomy. W. B. Saunders Co. BLACK, L. B., MYERS, E. N., and RORKE, L. B. (1973) Archives of Otolaryngology,
98, 123-8. BRAITHWAITE, F. (1949) British Journal of Plastic Surgery, 2, 38. GORLIN, R. J., and PINDBORG, J. J. (1964) Syndromes of the Head and Neck. McGraw Book Co. Inc., 368-9. HORSTACLIUS, S. (1950) The Neural Crest. Oxford University Press, 7, 35. KEEN, J. A. (1955) South African Journal of Laboratory Clinical Medicine, 1, 197-202. KEITH, A. (1909) British Medical Journal, 2483. KLEINASSER, O. (1964) German Journal of Laryngology and Otolaryngology, 43, 344. MCKENZIE, J. (1958) Archives of the Diseases of Children, 33, 477. PEARSON, A. A. (1967) Development of the Ear. American Academy of Ophthalmology and Otolaryngology. POSWILLO, D. E., and SOPHER, D. (1972) Nature, 269, 460.
(1973) British Journal of Oral Surgery, 3, 303, 327. ROGERS, B. O. (1968) Craniofacial Anomalies. J. B. Lippincott Co., Philadelphia. RUBEN, A. (1967) Handbook of Congenital Malformation. W. B. Saunders Co., Philadelphia. SMITHELLS, R. W., and LECK, I. (1963) Lancet, 1, 1095.
THOMPSON, A. (1845) Proceedings of the Royal Society, Edinburgh, 1, 433. WRAGG, L. E. (1970) Archives of Oral Biology, 15, 705-19. WOOD-JONES, F., and I-CHAUN, W. (1934) Journal of Anatomy, 68, 525-33. The Nottingham Hospital for Women Peel Street Nottingham NGi 4GP
1269
