MANDIBULO-FACIAL DYSOSTOSIS (TREACHER COLLINSSYNDROME)

BY

JOHN McKENZIE and JOHN CRAIGFrom the Departments ofAnatomy and of Chuld Health, University ofAberdeen

(uCEcVED FOR PUBUCATION FEBRuARY 3, 1955)

Mandibulo-facial dysostosis has been describedwith increasing frequency in recent years. Onceknown it is readily recognized and may be morecommon than is sometimes imagined.We describe in this article a case seen in a newly-

born infant who died at the age of 21 months and inwhom careful dissections were made of the facialregion.The infant (A.R., 456/1954) was admitted to the Royal

Aberdeen Hospital for Sick Children at the age of 2 weeks

He would take several drachms of his feed, then fallasleep; there was no vomiting and the bowels movedwell. The child at 2 weeks weighed 5 ib. 7 oz.No abnormalities were found about the heart or lung.

No masses were felt in the abdomen. On admission itwas noted that the baby was a 'bird-like crature withrather curious eyes and a receding chin'; the nostrils weresonmwhat small; there was hypoplasia of the malarbones; the ears were rather low set with some failure ofcartilage development, and appeared too big; the tongueseemed a little lare and was held towards the back of

F;c. --

because he failed to feed easily. The infant was bomof a healthy father and mother; the father had beenoperated on for harelip in childhood; there was a brotherof 3 years who was alive and well. No history of anyabnormality suggestive of dysostosis was elicited. Theinfant was bom at full-time, weighed 5 lb. 11 oz., andbreathed well after birth. He was fed from the beginningwith the bottle on half-cream National dried milk. Inthe second week the child began to feed with difficulty.

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the mouth. The eyes slanted downwards at the outerends; there was bending of the lower canthus at thejunction of its inner two-thirds and outer third; the eye-lashes in the upper lid and in the outer third of the lowerlid were normal; they were rather scanty in the medialtwo-thirds of each lower lid. The appearances of theinfant are seen in Figs. 1 and 2. The arms and legs movedwell. The palate was high-arched. The followingwere the body measurements:

Head cicumference . .Maximum head length ..Maximum head breadthFace lengthFace breadth . .

Nasion-alveolus ..Chin-occiput .

Chin-vertexStanding height ..

. . 350 mm.117 mm.I100 mm.54 mm.54 mm.37 mm.129 mm.

. . 124 mm.

. . 475 mm.

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Sitting height .. .. .. .. 350 mm.Biacromial width .. .. .. 132 mm.Bitrochanteric width .. .. .. 83 mm.

Fontanelle Anteroposterior 25 mm.f Coronal .. 30 mm.

Palpebral fissure .. .. .. 20 mm.Ear length R. 35 mm., L. 33 mm.Ear breadth .. .. R. 23 mm., L. 22 mm.

Radiographic examination of the skull added nothingto our knowledge of the bony state; there was poorsuction of an opaque meal. The oesophagus and fundusof the stomach were normal in outline.

Feeding continued to be difficult and attempts to feedby different tvpes of teat and by spoon were also un-successful, so that the infant had to be fed by catheter.The infant appeared to suck but the milk just dribbledout of the mouth. This difficulty continued for a monthand then quite suddenly feeding by bottle, which hadbeen constantly attempted, began to be successful,although some milk was constantly lost through apparent

postero-lateral projection for the upper attachment ofthe masseter. It did, however, allow the lower orbitalmargin to fall away laterally, thereby causing obliquityof the palpebral fissure. The squamous temporal bonewas smaller than normal. the deficiency being made upby the surrounding bones and by a small extra plaquebetween the temporal and the parietal bones. The headof the mandible, elongated antero-posteriorly instead oftransversely, was separated from a shallow articularfossa by a normal cartilaginous articular disc; there wasno articular eminence; the coronoid process of themandible was everted while the body was foreshortenedand receding.

Within the middle-ear, the incus and stapes wereabsent, but the middle-ear cavity and intemal ear werenormal.

There was no parotid gland.The musculature of the face and head was nowhere

deficient; indeed, it was unusually well developed, therebeing many extra muscle bundles in the facio-platysmalsheet and a tendency for the individual muscles in themasticatory group to become confluent.The maxillary artery (Fig. 4), after supplying normal

FIG. 3-

inability to swallow properly. In spite of continuedattempts to keep him on a feed containing the rightamount of calories, he failed to gain weight. Anoccasional cyanotic attack occurred, and he died at theage of 10 weeks.A post-mortem examination showed that the body

was that of a poorly nourished male child. The brainwas of normal size and showed no notable externalabnormality: the lungs showed extensive patchy basalcollapse with a few areas of consolidation; there was noevidence of inhaled material in the trachea or mainbronchi. The pericardial sac and the heart were normal;liver and spleen and intestinal tract were normal; therewas no lesion in the gall bladder, pancreas, adrenals orkidneys; the ureters were patent and the bladder normalin size.The head and neck were fully dissected. Abnor-

malities similar on both sides were revealed. Thezygomatic bone and zygomatic process of the temporalbone were absent (Fig. 3), but the maxilla, as well ascompleting the margin of the orbit, also provided a

FaM 4.

inferior dental, posterior superior dental and middlemeningeal branches, petered out before it reached thepterygo-maxillary fissure. The lower surface of thepalate was supplied by the posterior superior dentalvessel, while the nasal cavity received blood from a vesselwhich arose from the maxillary artery near the origin of theinferior dental artery, ran along the lower border of thelateral pterygoid muscle, entered the pterygo-palatine fossafrom behind and finally ran up to and through the spheno-palatine foramen into the nose. The infra-orbital

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artery was a branch of the ophthalmic artery. Themiddle meningeal artery (Figs. 4 and 5), after it enteredthe skull and before it divided into its two branches,produced a vessel which ran backwards and mediallyas if it were reaching out for the intemal carotid artery,but faded out behind the mandibular nerve.

FuL S.I

After Treacher Collins (1900) described twocases showing notching of the lower eyelids asso-

ciated with defective development of the malarbones, these features were regarded as the essentialcharacteristics of the Treacher Collins syndrome;but it is now realized that many other features suchas abnormalities of the mandible and of the ear may

be safely included under this title and that the slightanti-mongoloid obliquity of the palpebral fissures,occurring alone in a patient and causing no commentwhatsoever, is the minimal clinical manifestationof the same syndrome (Franceschetti and Klein,1949). After reviewing many of the published cases

and describing several others, these authors recog-

nized, as did Mann and Kilner (1943), that theessential lesion was a hereditary maldevelopment ofthe maxillary process and mandibular arch, and withthe data gleaned from clinical and x-ray examination,concluded that the cause of this congenital abnor-mality was 'an inhibitory process occurring towardsthe seventh week of the embryonic life and affectingthe facial bones deriving from the first visceral arch'.They assumed the aetiology to be 'a disturbance ofthe organization center'.

Hovels (1953a), in a more extensive survey of the

literature, graded the recorded cases to form a series,from the simplest form, showing only obliquity ofthe palpebral fissures, to the most extensive, whichincluded deformations such as agnathia. Hisattempts (Hovels, 1953b) to find the cause of theabnormality were based on the work of authorssuch as Horstadius (1950) who found that thevisceral arches were derived in their entirety fromthe rostral end of the neural crest where areas couldbe mapped out corresponding to these derivatives.Extirpation of these areas resulted in deficiencies inor the absence of the corresponding arches. Hovelsmaintained that some defect in the neural crest arearesponsible for the first visceral arch produced thestructural abnormalities of the Treacher Collinssyndrome.

This theory, however, will not withstand criticalexamination. For example, the most frequentlyaffected part of the face is the zygomatic bone whichis the proximal part of the maxillary process; if, asHovels suggests, it were predetermined within theneural crest that there was to be no zygomatic bone,then surely the maxillary process would not be longenough to meet and fuse with the nasal processes.Yet they do; there is no cleft palate, harelip, orinterference with the naso-lacrimal duct. Theobservations obtained clinically and radiologicallymust be supplemented by the detailed anatomy ofthe deeper tissues in the region of the abnormalitybefore theories as to its origin are put forward.This has been difficult because the syndrome is quitecompatible with life and only occasionally can a casebe thoroughly investigated. Lockhart (1929), whofirst dissected the abnormality, did not correlate hisfindings with any clinical abnormality, and con-sequently his article has been overlooked as a sourceof information on the anatomy of the syndrome.He drew attention to the association of absence ofthe zygoma with abnormalities in the middle ear andwith minor alterations in the muscles of mastication.Even in Hovels' work there is no mention of thecondition having been dissected. It is obvious whenthe abnormalities in the arteries supplying the tissuesderived from the maxillary process are consideredthat this portion of the first visceral arch sufferedfrom a temporary deficiency in its blood supply byocclusion or failure of the maxillary artery at anearly age. However, while the zygomatic bone hadno alternative means of nourishment at the criticalstage of its ossification and therefore did notdevelop, the maxilla borrowed a blood supply fromthe internal carotid artery through the ophthalmicartery to tide it over until a secondary source wasavailable from the root of the maxillary artery.

According to Keibel and Mall (1910-12), the

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normal development of the arteres derived from thefirst aortic arch is as follows (Fig. 6): Three arteriesare produced from the first aortic arch: (1) thesupra-orbital, later to become the middle meningalartery, (2) the infra-orbital reprqsenting the maxillaryand (3) the mandibular or inferior dental. With

associad with the absence of the stapedial than foreither of the other two first arch vess. Could thedevelopment of these vessels not be as shown inFig. 7? Instead of the supra-orbital, infra-orbitaland mandibular vessels arising fanwise from asinge point, let them arise separately; and let the

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the disappearance of the first arch, these three vesselsare all maintained by the stapedial artery, a short-lived vessel in the human embryo passing through thestapes, supplying the structures derived from theposterior end of the second visceral arch, and affixingitself to the stem of the supra-orbital artery. Whenthe external carotid artery develops it takes over

these three vessels again and the stapedial arterydisappears. The two vessels whose absence is in-volved in the production of the Treacher Collinssyndrome are the stapedial and infra-orbital arties,yet according to the foregoing description there isno more reason for the infra-orbital vessel being

infra-orbital artery, since it originally runs deep to themandibular nerve, be the vessel which receives thestapedial artery and depends on it to a greaterextent than do the others for its survival. Withoutthe help of the stapedial artery the middlem Ialartery could still continue to function by retainingits connexion with the dorsal aorta. This is signi-ficant when it is remembered that the specimendescribed here had an aberrant vessel from themiddl meninl artery which could have anas-tomosed with the internal carotid artery at one timeround the back of the mandibular nerve. Themandibular artery could likewise survive from its

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MANDIBULO-FACIAL D YSOSTOSIS 395

connexion with the ventral aorta or the developitngexternal carotid. In addition to describing what isthe more probable sequence of events in the develop-ment of the vessels in this region, we can also showthat there is still in the adult a remnant of the firstaortic arch, namely, that part ofthe middle meningealartery between its origin from the maxillary and apoint near its bifurcation. That small piece of firstaortic arch between the infra-orbital and mandibulararteries is transferred to the middle meningeal arteryas well when the infra-orbital forms its anastomoticloop around the mandibular nerve to lie superficialto it as in the adult.

It seems, then, that the original lesion in theTreacher Collins syndrome lies with the stapedialartery; its absence will give defects of the stapes andincus and maldevelopment of the first arch vesselsusually involving but not necessarily restricted tothe maxillary: failure of the inferior dental to retainor find an auxiliary source of supply will give con-comitant abnormalities of the mandible. Thepossibility of a normal stapedial capable of supplyingthe posterior end of the second visceral arch and nomore will account for the defects of bones and softtissues being confined to the face. We can in thisway account for all recorded abnormalities con-stituting the Treacher Collins syndrome, howeversevere, or however variable, and fturther we canpoint to the sixth week of intra-uterine life as beingthe age for the inception of the abnormality, i.e.imediately after the formation of the primitiveface.

Smr

A typical case of the Treacher Collins syndrome(mandibulo-facial dysostosis) is described with theclinical features and the abnormal details of itsanatomy.A fresh suggestion regarding the cause of the

abnormality is put forward, based chiefly on thearterial abnormalities present in this case, viz. thata defect of the stapedial artery causes maldevelop-ment not only in its own field of supply but also inthe region of the first visceral arch whose vessels thestapedial artery normally supports during the criticalphase between the disappearance of the first aorticarch and the full development of the external carotidartery, just after the formation of the primitiveface.The normal development of the arteries in and

near the first visceral arch is reconsidered andmodified.

We are indebted to Professor R. D. Lockhart for hisinterest and advice during the investigation, to Mr. W.Cruickshank for the illustrations and to Mr. R. G. M.Drummond for the photographs.

REFERENCES

Collins, E. T. (1900). Trans. ophthal. Soc., 20, 190.Franechetti, A. and Klein, D. (1949). Acta ophthal., Kbh., 27, 143.Hdrstadius, S. (1950). Thme Neural Crest. London.Hovels, 0. (1953a). Z. Kimderheilk, 73, 532.

(1953b). Thid., 73, 568.Lockhart, R. D. (1929). J. Aat., 63, 233.Keibel, F. and Mall, F. P. (1910.12). Manual ofHuman Embryology.

PhiLaddphiabMann, I. and Kilner, T. P. (1943). Brit. J. Opkthal., 27, 13.

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