The François Dyscephalic Syndrome and Skin Manifestations

THE F R A N Ç O I S D Y S C E P H A L I C S Y N D R O M E A N D

S K I N M A N I F E S T A T I O N S

J U L E S F R A N Ç O I S , M . D . A N D J E A N P I E R A R D , M . D .

Ghent, Belgium

In 1958 one of us1"3 described a syndrome characterized by seven main signs :

1. Dyscephaly with bird's head—Scapho-, or more often brachycephaly, aplasia of the mandible with a thin and tapering nose and hence a distinctive physiognomy, which gives all affected subjects a "family" resemblance to one another.

2. Dental anomalies—Teeth absent or malformed, irregularly set with hiatodonty.

3. Proportioned dwarfism. 4. Hypotrichosis—Particularly obvious in

the region of the scalp (alopécie areas), the eyelashes and eyebrows, but also possibly affecting the beard and axillary and pubic hair. The hair is fine and generally of clear color.

5. Skin atrophy—Usually affecting the skin of the face and especially that of the nose.

6. Bilateral microphthalmia. 7. Congenital cataracts—Bilateral, total or

incomplete. There is often nystagmus, and also con-

vergent or divergent strabismus. There are no anomalies of the ear, as in

the first arc syndrome; or anomalies of the eyelids, as in mandibulofacial dysostosis ; or muscular atrophy with chronic arthritis and premature arteriosclerosis, as in progeria ; or onychoid lesions, as in certain forms of ecto-dermal dysplasia; or anomalies of the ex-tremities, as in certain other dyscephalias. There is no mental retardation, both neuro-logic and psychologic examinations usually being negative.

Since the initial communication of one of

From the Ophthalmological Clinic and Dermato-logical Clinic of the University of Ghent.

Reprint requests to Professor Jules Francois, Ophthalmological Clinic, University Hospital, De Pintelaan, 135, B 9000 Ghent, Belgium.

us ( JF) , numerous cases have helped to con-firm the existence of this syndrome.4"55

Most of the cases described are single with no sex predominance. Heredity is diffi-cult to demonstrate, as the patients have no progeny. It is nevertheless very probable ; in fact, Waardenburg,56 in 1959, observed the condition in monozygotic twins. Also, it has been noted in several members of the same family.*' 1 6 ' 3 9 , 5 7 Moreover, consanguinity of the parents has been reported three times ( 6 % of the cases) . 4 ' 1 6 ' 1 9

The syndrome is no doubt due to a distur-bance in development which occurs in the fifth or sixth week of embryonic life and which particularly affects the ventral part of the cephalic extremity while also spreading to certain ecto- and mesodermal anlagen.

The skin involvement in the François dys-cephalic syndrome was reported from the outset but has never been studied histologi-cally. We therefore felt it useful to report two new cases which we examined in detail from this point of view.

C A S E R E P O R T S

Case 1—Miss St. A , aged 38 years, was seen in March, 1969, (Fig. 1). Her vision had always been poor. Ophthalmic examination showed bilateral mi-crophthalmia (Fig. 2) . The corneal diameter is 8.75 mm on the right and 9 mm on the left. Echography shows that only the anterior segment is too small, the posterior segment being of normal length. In fact, the length of the anterior segment is only 2.46 mm on the right and 2.56 mm on the left ; the thick-ness of the lens is 4.01 mm on the right and 4.25 mm on the left, and the length of the vitreous, 15.72 mm on the right and 15.05 mm on the left, so that the overall length of the eye is 22.54 mm on the right and 22.21 mm on the left.

The anterior chamber is shallow. There are rem-nants of the pupillary membrane. Some isolated opacities are found in the lens cortex, but no cata-ract proper. The vitreous is very clear. In the right fundus on the temporal side there is a small parapa-pillary atrophic area of triangular shape (Fig. 3) . There is macular degeneration of half a disk diam-

1241

1242 AMERICAN JOURNAL OF OPHTHALMOLOGY JUNE, 1971

Fig. 1 (François and Pierard). François' dyscephalic syndrome.

eter in size, with two small grains of pigment at the center of the depigmented background. The retina is dystrophic and is covered with pigment dust. On the left, we find a retrovascular pigmented stria on the nasal side of the optic disk parallel to the papil-lary border (Fig. 3) . Macular degeneration is also present. The retina is dystrophic and dusted with fine pigment.

The ocular tension is 42.1 mm Hg on the right and 29 mm Hg on the left.

Gonioscopic examination shows a persistence of mesodermal tissue of the embryonal type in an open iridocorneal angle in both eyes.

The visual acuity is 8/10 on the right with - 1.50 Ô sph .C- 1-50 Ô cyl. ax. at 170°. It is 1/10 on the left with sphere — 2 ô sph.

Both visual fields are markedly and concentri-cally narrowed.

Color vision is normal. The electroretinographic response is extremely subnormal on both sides. A goniotomy was performed in both eyes which nor-malized the ocular tension which is now 17.3 mm Hg on the right and 18.5 mm Hg on the left.

From the systemic point of view, we found the following signs in this patient:

Dyscephalia—The bird profile is typical. The nose is small, thin, pointed, and umbilic. The base of the nose is rather wide. The palpebral fissures are small and contramongoloid. The lips are thin and somewhat drawn in. The mandible is aplastic.

Otolaryngology—Examination shows very nar-row nasal fossae. There is a submucosal buccal fis-sure. The auditory meatuses are considerably re-duced. The audiogram is subnormal. The voice is raucous and the articulation jerky.

X-ray studies—These show the cranium, though a little small, to be otherwise normal. The facial struc-ture overall is insufficiently developed. The orbits are narrow. The frontal sinuses are non-existent, the maxillary sinuses tiny. Both maxillary bones are very little developed. The lower maxillary bone is aplastic and the ascending branch is especially atrophic. We find a minor coronoid apophysis but no condular or articular apophysis.

Dental anomalies—These must have been severe ; the teeth progressively cracked, and between the

Fig. 2 (François and Pierard). Case 1. Bilateral microphthalmos.

VOL. 71, NO. 6 DYSCEPHALIC SYNDROME 1243

Fig. 3 (François and Pierard). Case 1. Left: Right fundus, parapapillary atrophic area and macu-lar degeneration. Right : Left fundus, renovascular pigmented stria at the nasal side of the disk.

ages of 20 to 25 years they were removed. The vault of the palate is narrow.

Dwarfism—The patient stands 1.57 m and weighs 65 kg.

Hypotrichosis—The hair is sparse, fine, clear, chestnut in color. Its length never reaches more than a few centimeters. (Fig. 4) . The eyelashes are almost completely absent on the lower eyelids. There is pronounced alopecia of the eyebrows which are even absent laterally. The underarm, pu-bic, and vulva hair is absent. The skin of the limbs is dry and alopécie.

Skin atrophy—The skin of the face is fine and a little soft on palpation. It is distinctly thinner in the region of the nose where it is dotted with telan-giectases. The cheeks are also telangiectatic. The palms and the soles are yellowish. The soles are slightly keratotic. The nails are very convex.

Fig. 4 (François and Pierard). Case 1. short hair.

Fine and

''The thighs and the legs show a livedoid network which is more apparent on the right side laterally and around the knees.

Skeletal x-rays—The metacarpals are a little squat. There is camptodactyly of the fourth finger and the little finger on both sides and also brachy-phalangia of the middle phalanx of both index fin-gers. The middle phalanx of both little fingers is absent, and that of the fourth fingers is short and squat.

The long bones and the joints are normal. The second phalange of each of the last four toes is com-pletely missing on both sides. There is slight thoracic kyphosis with convexity to the right ht and L 5 are congenitally fused. There are signs of a deforming spondylarthrosis of the lumbar vertebrae.

General development—The mammary glands are rudimentary. The hands are small. The fourth fin-gers and the little fingers, which were operated on in childhood, are highly retracted like a claw.

Karyotype—Blood microculture is normal (2n = 46 = 44A + X X ) .

Histologic examination—We made two biop-sies, the first in the apparently normal skin of the forearm, the second in the temporal region where the tegument is thinned.

Biopsy of forearm showed normal epidermis. The collagen fibers are undulating, often tangled and oriented in all directions with an obvious lack of cohesion. Hair follicles are absent The seba-ceous glands are small. The sweat glands are nor-mal. The elastic fibers are fragmented in short seg-ments, particularly in the upper and middle dermal layers (Fig. 5) . Deeper down, they are thicker and some appear bloated, tortuous, or piled as tangled clusters.

Skin biopsy from the temporal region showed no epidermal lesions, but the hair infundibuia are plugged with keratin. Several follicles are enlarged


Fig. 5 (François and Pierard). Case 1. Apparently normal skin of the forearm. Fragmentation of the clastic fibers (Verhoeff stain, X350).

and devoid of hair. The sebaceous glands are rather voluminous. The sweat glands are normal. The collagen fibers are sometimes homogenized and lack cohesion, but their direction is less disordered than in the preceding preparation. Neither with hema-

toxylin-eosin nor with Masson's trichrome stain is there any trace of senile elastosis. The elastic fibers, however, show a variety of anomalies in the upper and middle dermal layers (Fig. 6 and 7) . Aldehyde-fuchsin shows, along with normally stained ele-

Fig. 6 (François and Pierard). Case 1. Atrophic skin of the temporal region. In the superior dermis alterations resembling these seen in actinic elastosis. (aldehyde-fuchsin stain, X350).


Fig. 7 (François and Pierard). Case 1. Atrophic skin of the temporal region. In the superior dermis, alterations resembling these seen in senile elastosis. In the middle dermis, elastic fibres forming tangled clusters (orcein stain, X140).

ments, thickened, swollen fibers with undulating contours. Some are strongly colored while others appear washed out. In places, the picture more or less recalls that observed in actinic elastosis (Fig. 8) . However, Verhoeff's staining does not confirm this comparison. Throughout the upper dermis— that is, in the zone where actinic elastosis is nor-mally located—the elastin does not take the stain, but show up as very pale granular clusters more or less spread out with imprecise contours on which fibrils of greyish or brownish hue sometimes are seen (Fig. 9) . Lower down, in the middle and lower dermal layers, staining for elastin again be-comes normal. The fibers here are black color but few in number. Some are thin, often fragmented or moniliform, others are thicker, tortuous, and form tangled clusters.

Case 2—The case of this 33-year-old man was published by Konstas and associates" in 1964. He presented with a typical François dyscephalic syn-drome (Fig. 10). The family history was negative with no consanguinity of the parents.

Ophthalmic examination shows both eyes to be microphthalmia the corneal diameter being 10 mm. They had been operated on for congenital cataract at the age of four months. For five years the pa-tient had suffered from bilateral glaucoma. Bilateral nystagmus is also noted.

The corneas show bullous, principally peripheral, edema. A secondary cataract membrane remains. The irises are atrophic. The eye fundus can not be explored. The vitreous shows signs of degenera-tion.

The ocular tension is 42.1 mm Hg on the right and 33.0 mm Hg on the left. Vision is 1/20 on the right, and 1/30 on the left after correction of aphakia

Fig. 8 (François and Pierard). Case 1. Atrophic skin of the temporal region. In the superior dermis of the temporal region. In the superior dermis the elastin is very badly stained. In the middle dermis (down at the right) normal staining of the elastic fibers (Verhoeff stain, X140).


Fig. 9 (François and Pierard). Case 1. Atrophie skin of the temporal region. Middle and inferior dermis. Very scarce elastic network in the inferior dermis (Verhoeff stain, X140).

(sph. -f- 19 ô on the right, sph. -4- 16 ô on the left). The visual fields show concentric narrowing.

In both eyes we performed a Scheie fistulizing operation which normalized the tension. This is now

Fig. 11 (François and Pierard). Case 2. Alopécie patches in the scalp.

9.S mm Hg on the right and 6.8 mm Hg on the left. Vision has improved to 3/10 on the right and 2/10 on the left. The fundi appear normal although it is difficult to explore them.

There is obvious aplasia of tlie mandible. The whole facial structure is too small in relation to the cranium. The nose is thin, pointed and highly curved. The profile is that of a bird.

The teeth which were malformed have all been extracted.

The scalp and the beard have alopécie patches of varied shape and size (Fig. 11). Those of the scalp are more or less atrophic and finely wrinkle on palpation. The follicular orifices have disap-peared. Eyebrows and lashes are rare. Axillary hair is scanty, that of the pubis normal.

The skin is thinned, particularly over the upper thorax.

Proportioned dwarfism exists—height, 161 cm ; girth, 161 cm; and weight 60 kg.

Fig. 10 (François and Pierard). Case 2. François dyscephalic syndrome.


Fig. 12 (François and Pierard). Case 2. Apparently normal skin of the forearm. Absence of cohesion of the collagen fibers (Masson's trichrome, X560).

X-ray studies of the skull show that the man-dible is too small and too short The whole of the facial structure is too small in relation to the cranium.

Cytogenetic examination showed no numerical or structural anomaly of the chromosomes.

Histologic examination—A biopsy was taken from the forearm where the skin is normal in appearance and another from an alopécie patch of the scalp.

Biopsy of the forearm showed the epidermis to be thin. The mucous body has only two to three cell layers. The stratum corneum is foliated. The upper dermal layer shows no anomaly, but the middle and deep dermal layers have a loose struc-ture. The collagen fibers are thin and oriented in all directions. Cohesion is completely lacking (Fig. 12). The fibers appear disordered and tangled, or swirling. Adnexa are rare as are the capillaries.

The elastic tissue is normal in appearance in the outer dermal layer. Lower down, as in the pre-ceding case, it is often fragmented into short seg-ments. The number of elongated fibers is clearly reduced. In the deep dermal layer, elastin is less fragmented, but often forms tangled clusters and skeins.

Biopsy from an alopécie patch on the scalp shows that the epidermis has retained its pattern and its interpapillary buds are still present. The stratum corneum is thick and lamellar. The granular layer is missing throughout almost the entire section. Pigmentation is pronounced.

The intact papillary dermal layer is subtented by a layer of senile elastosis. As in the preceding sec-tion, there is considerable laxity of the dermal texture. Some hair follicles remain, but their in-

fundibula are enlarged by keratotic plugs, which extend even in the depth of the follicles, the hairs becoming very thin and atrophic.

Elastin—Under the well stained band of senile elastosis the middle and deep dermal layers show, with aldehyde-fuchsin and orcein staining, a feebly chromatic elastic network consisting of fibers frag-mented into short segments or much undulating which give them a moniliform aspect. Clusters of very fine juxtaposed or intertwined fibers are also seen. At any rate, the thick and strongly stained fibers normally found in the deep dermal layer are absent. Those that are observed are rare, thinner and more twisted. Here and there, small granular clusters with fine fibers are seen. Under the wide band of senile elastosis, the elastin shows a patho-logical aspect. The fibers are fragmented, monili-form, or tangled in the middle dermal layer, rare, thin and often barely stained in the deep dermal layer.

D I S C U S S I O N

The involvement of the skin in the Fran-çois dyscephalic syndrome is far from neg-ligible. Hypotrichosis is very characteristic. Always extensive, sometimes generalized, as in our first case, or disseminated in the form of patches with an atrophic aspect, as in the second case, it is accompanied by a certain degree of atrophy of the facial skin, which is dry, fine, soft and riddled with telangiec-tases. This dryness and fineness of the skin can also be found in other regions of the


body. We also noted the livedoid network in the lower limbs which we observed in our first case and which one of us (JF) ob-served in his first published case.

Histologic examination also demonstrates the presence of a generalized disturbance in the connective tissue. These modifications are observed not only at the sites where the tegument is objectively impaired but also some distance away in regions where no clin-ically detectable anomaly is present.

In the apparently healthy skin, they con-sist of absence of cohesion of the collagen fibers which are tangled and oriented in all directions and of fragmentation of the elas-tic fibers into short segments. In the zones where the skin is clinically modified, they are reflected in the upper and middle dermal lay-ers by the same lack of cohesion of collagen and especially by the variability in the as-pects of the elastic fibers : some are frag-mented, moniliform, or tangled in tight clus-ters; others are swollen and show irregular or imprecise contours and uneven staining affinities. In the deep dermal layer they are rare, often narrow, or even thin and some-times take little stain. These histologic changes in the connective tissue explain the sensation of softness given by palpation of the facial skin of our patients.

On the other hand, it seems that inflamma-tion plays only an accessory part in the pro-cess, since the infiltrates seen in the first case are nearly absent in the second one.

It follows from these findings that the François dyscephalic syndrome is related in some way to congenital changes in elastin. They are nevertheless of quite a different nature from those observed in pseudoxan-thoma elasticum. While the changes in the latter become manifest quite clearly on rou-tine staining by a violaceous hue with hema-toxylin-eosin and by an orange-red hue with Masson's trichrome, this is not true in the dyscephalic syndrome where the elastin is not brought out with these stains. With spec-ific staining methods, the appearances also differ appreciably from those seen in pseu-doxanthoma. Moreover, no calcium is seen

on staining with von Kossa. The presence of elastic alterations in the

skin must make one suspect the possibility of alterations in Bruch's membrane, as in the Groenblad-Strandberg syndrome where an-gioid striae are found.

In the François1 syndrome, the fundus often cannot be explored because of microphthal-mia and primary or secondary cataract. This explains why few observers mention the re-sults of ophthalmoscopic examination.

Be this as it may, two histopathologic ex-aminations of the eyes of patients, with the François syndrome are known: Wolter and Jones (1965) 3 1 do not appear to have studied Bruch's membrane, but Blodi and Braley (1966) 3 3 report numerous drusen of the vitreous lamina.

Ophthalmoscopic anomalies of the fundus have been reported by a dozen authors: pe-ripapillary atrophy,9' 1 1 ' 5 8 , 5 9 or speckled aspect of the fundus.4 2'4 8

In one case, François (1959) 3 saw a colo-boma at the entrance of the optic nerve on the right, and on the left, peripapillary le-sions in the form of foci of cicatricial cho-rioretinitis. In another case, he reported anomalies of the macular region which cov-ered an area of four disk diameters. Two equally wide parts could be distinguished. The first, parapapillary, was irregularly de-pigmented and showed a marbled and yel-lowish aspect. The second part, temporal, was heavily pigmented and was occupied by dusty, tiny, brownish pigments which were distributed homogeneously and progressively diminished in number towards the periphery, while they accumulated on the central side where they suddenly stopped tracing a verti-cal irregularly undulated line.

Carones (1961) 1 0 saw a similar lesion. The temporal half of the posterior pole showed brownish, dusty pigmentation cover-ing a half-moon space from where it pro-gressively fell off towards the periphery.

Calmettes and associates ( I960) 8 observed diffuse atrophy of the pigment epithelium with macular cracks of a red brick color.

Gernet (1964) 2 4 reported horizontal reti-


nal folds in the macular region in both eyes,

their prominence being at the most one diop-

ter. These may well be changes in Bruch's

membrane as we observed in a Groenblad-

Strandberg case.

Other lesions of the fundus have been de-

scribed: disseminated pigmentation, foci of

chorioretinal atrophy,4 2'6 0 greyish macular

zone centered by a red fovea.5 9

Finally, Guyard and associates (1962), 1 6

who observed the syndrome in a father and

daughter, saw a coloboma of the choroid in

the right eye of the latter and in the left eye,

outside the disk, glial hyperplasia recalling

proliferating retinitis with pigmented

patches of cicatricial chorioretinitis. In add-

tion there were cracks in the choroid recall-

ing angioid striae.

To sum up, several observations3' 8 ' 1 6 ' 2 4 ' 3 3

mention appearances in the fundus which

may be attributed to lesions of Bruch's mem-

brane. Although the number of the observed

alterations is few, they must encourage one

to look for lesions in a more systematic man-

ner.

Be this as it may, these lesions of the fun-

dus are additional to the lesions of elastic tis-

sue which we have noted in the skin. But,

contrary to the elastic pseudoxanthoma of

Groenblad-Strandberg where the disturbance

in elastic tissue is the major change from

which the others stem, the elastic anomaly in

the dyscephalic syndrome constitutes only one

of the facets of a more general disturbance in

development affecting several systems during

embryonic formation.

S U M M A R Y

Two typical cases of the François dysce-

phalic syndrome are reported and the impor-

tance of the skin involvement is stressed.

Connective tissue lesions and especially elas-

tin changes were demonstrated by histologic

examinations revealing anomalies even in

apparently healthy skin.

R E F E R E N C E S

1. François, J. : Un nouveau syndrome. Dy-scéphalie avec tête d'oiseau et anomalies dentaires,

nanisme, hypotrichose, atrophie cutanée, microphtal-mie et cataracte congénitale. Boll. Oculística. 25:161, 1958.

2. François, J. : A new syndrome. Dyscephalia with bird face and dental anomalies, nanism, hypo-trichosis, cutaneous atrophy, microphthalmia, and congenital cataract. Arch. Ophth. 60:842, 1958.

3. François, J. : Congenital Cataracts. Springfield, Thomas, 1963, p. 278.

4. Jalbert, P , Gilbert, Y , Leopold, P., Mouri-quand, C, and Beaudoing, A. : Syndrome d'Haller-mann-Streiff-François. A propos d'une nouvelle ob-servation associée à une anomalie caryotypique. Pédiatrie 23:703,1958.

5. Cambiaggi, A.: Sindrome di Hallermann-Streiff con eterocromia di Fuchs. Boll. Oculística 37:365, 1958.

6. Bueno, M.: Sindrome de Hallermann-Streiff-François. A proposito de una presentación familiar. Bol. Soc. Vasco. Navarra 1:21, 1960.

7. Bonamour, G, and Leopold, P., Syndrome dy-scéphalique avec tête d'oiseau (syndrome de Fran-çois). Bull. Soc. Opht. France 60:85, 1960.

8. Calmettes, L., Deodati, P , Cadenat, H , and Bechac, G. : La dysmorphic mandibulo-faciale type François (à propos d'un cas). Rev. Oto-Neuro-Opht. 32:275 1960.

9. Falls, H. F , and Schull, W. H. : Hallermann-Streiff syndrome. A dyscephaly with congenital cataracts and hypotrichosis. Arch. Ophth. 63:409, 1960.

10. Carones, A. V. : Syndrome dyscéphalique de François. Ophthalmologica 142:510, 1961.

11. Van Balen, A.T.M.: Dyscephaly with mi-crophthalmos, cataract and hypoplasia of the man-dible. Ophthalmologica 141:53, 1961.

12. Roth, L.: A propos du syndrome de Haller-mann-Streiff. Bull. Soc. Opht. France 62:500, 1962.

13. Tazia, A. : Un cas du syndrome nouveau de François. Soc. Maroc. Ophthal, June, 1962.

14. Ardouin, M , Urvoy, M , and Bezier, M. J. : Dyscéphalie avec tête d'oiseau, cataracte bilatérale et kératite en bandelette. Bull. Soc. Opht. France 62: 438, 1962.

15. Sakaue, E. : Hallermann-StreifFs syndrome. J. Clin. Ophth. Tokyo 16:653, 1962.

16. Guyard, M , Perdriel, G, and Ceruti, F. : Sur deux cas de syndrome dyscéphalique à tête d'oiseau. Bull. Soc. Opht. France 62:443, 1962.

17. Larmande, A , Gillot, F , Dalaut, J. J, Cohen, J. P , and Schaeffer J. C. : Dyscéphalie à tête d'oiseau (syndrome d'Hallermann-Streiff-François). Pédi-atrie 17:313,1962.

18. Ponte, F.: Further contributions to the study of the Syndrome of Hallermann and Streiff. Oph-thalmologica 143:399, 1962.

19. Manzitti, E , and Alezzandrini, A. A. : Syn-droeme dyscéphalique de François, Ann. Oculistique 196:456,1963.

20. Roca, R. : Discefalia con cabeza de pajaro (sindrome de François-Hallermann-Streiff). Boll. Soc. Val da Ped. 5:17,1963.

21. Konstas, P , Batsolas, B , Stangos, N , and Tsitros, A.: Spndrome de François. Arch. Ophth. Hetair. Boreil hellad. 13:159, 1964.

1250 AMERICAN JOURNAL OF OPHTHALMOLOGY JUNE. 1971

22. Apollonio, A , and Zoldan, T.: Su alcuni casi di malformazioni cranio-facciali in associazione ad altre alterazioni saisoriali. Boll. Oculist. 43:76, 1964.

23. Forsius, H , and de la Chapelle, A.: Dys-cephalia oculo-mandibulo-facialis. Two cases in which the chromosomes were studied. Ann. Paediat. Fenn. 10:288, 1964.

24. Gernet, H. : Ueber Mikrophthalmus, Macu-laveränderungen und Refraktion bei einem Fall von Dysostosis mandibulo-facialis Hallermann-Streiff (Dvskephalie-Syndrome François). Klin. Mbl. Augenheilk. 144:887, 1964.

25. Torres Marty, L , and Dolcet, L. : Síndrome de François-Hallermann-Streiff. Arch. Soc. Oftal. hisp.-amer. 24:474, 1964.

26. Watrin, E. : Un nouveau cas de syndrome de François. Bull. Soc. Opht. France 64:87, 1964.

27. Younessian, S, and Ammann, F. : Deux cas de malformations cranio-faciales. 1 Microphtalmie (nanisme oculo-palpébral) avec dysostose cranio-faciale et status dysraphique. 2. Dysmorphic mandi-bulo-oculo-faciale (syndrome d'Hallermann-Streiff). Ophthalmologica 147:108, 1964.

28. Guerineau, P , and Plassart, H. : Syndrome dyscéphalique de François (à propos d'un cas chez un nourisson de race maure). Arch. Fr. Péd. 22: 882, 1965.

29. Hoefnagel, D , and Benirschke, K. : Dy-sccphalia mandibulo-oculo-facilais (Hallermann-StreifT-syndrome). Arch. Dis. Child. 40:57, 1965.

30. Lamy, M., Jammet, M. L , Maroteaux, P , and Ajjan, N. : La dyscéphalie (syndrome de Haller-mann-Streiff-François). Arch. Fr. Péd. 22:929, 1965.

31. Wolter, J. R , and Jones, D. H.: Spontaneous cataract absorption in Hallermann-Streiff Syndrome. Ophthalmologica 150:401, 1965.

32. Bengisu, N , Basar, D., and Idil, M. K.: A case of oculo-mandibulo-facial dyscephaly (the Fran-çois svndrome). VI Türk. Oftal. Kong. Bult., 1966, p. 274.

33. Blodi, F. C, and Braley, A. E. : Die Augen-veränderungen im François-Hallermann-Streiff Syn-drom. Proc. XX Intern, congr. Ophth, Munich, 1966, p. 981.

34. Verger, P , Corcelle, L , Guillard, J. M , and Descamp, F. : Sur deux cas de syndrome de Fran-çois. Ann. Pédiat. 42:203, 1966.

35. Gellis, S. S, and Feingold, M.: Picture of the month: Hallermann-Streiff svndrome. Am. J. Dis. Child. 111:635, 1966.

36. Janear, J. : Hallermann-Streiff-François syn-drome (dyscephalia mandibulo-oculo-facialis). J. Ment. Def. Res. 10:255, 1966.

37. Kurlander, G. J, Lavy, N. W , and Camp-bell, J. A. : Roentgen differentiation of the oculo-dento-digital syndrome and Hallermann-Streiff syn-drome in infancy. Radiology 86:77, 1966.

38. Niwa, I , and Itoi, M. : A case of mandibulo-facial dysmorphia. The Hallermann-Streiff syn-drome. Rinsho Ganka 20:65, 1966.

39. Sanchez, M. B. : Síndrome de Hallermann-Streiff-François. A proposito de une presentación familiar. Bol. Soc. Vasco-Navarra Pediat. 1:21,1966.

40. Srivastava, S. P , Jain, S. C, and Nema, H. V.: Mandibulc-oculo-facial dyscephaly. Brit. J. Ophth. 50:543, 1966.

41. Juglio, N. : Su di un caso di sindrome di Hal-lermann e Streiff (Nuova sindrome di François). Ann. Ottal. 93:655,1967.

42. El Massri, A.: Dyscephaly with congenital cataract. Brit. T. Ophth. 51:352, 1967.

42. Koo, B. S, Rhee, S. V , and Kim, J. H.: A case of the Hallermann-Streiff syndrome. J. Korean Ophth Soc. 8:55, 1967.

44. Macciotta, A , Zanolla, L , and Bertoni, G. : Contributo alla conoscenza délia discefalia mandi-bulo-oculo-faciale. Ann. Ital. Pediat. 20:209, 196..

45. Paufique, L , Diderlaurent, A , Cotton, J. B , and Maugery, J. : Trois nouveaux cas de syndrome de François (dyscéphalie avec tête d'oiseau). Bull. Soc. Opht. France 67:315, 1967.

46. Zolog, N , Lupu, C, Atanasescu, F, and Habenicht, G. : Syndrome dyscéphalique de François avec tétralogie de Fallot. Revue Oto-Neuro-Opht. 39:65,1967.

47. Salado-Marin, F. : The François syndrome. Arch. Soc. Oftal. Hisp.-amer. 27:473, 1967.

48. Borghi, A , Brancato, R , Maiello, M , and Montali, T. : Discefalia mandibulc-oculo-faciale o nuova sindrome di François. Rass. neur. Veg. 22: 204, 1968.

49. Caspersen, I , and Warburg, M.: Hallermann-Streiff-syndrome. Acta Ophth. Kbh. 46:385, 1968.

50. Gaudier, B, François, P , Ponte, C, Nuyts, J. P , and Bombart, E. : Encéphalopathie infantile et dysmorphies complexes. III Le Syndrome de Haller-mann-Streiff-François. Soc. Méd. Nord, February 1968.

51. Walbaum, R , Woilliez, M , François, P , a m ! Mayolle, P. : Le syndrome de Hallermann-Streiff-François. Deux observations. Pédiatrie 23:787, 1968.

52. Kermarrec, J. : Syndrome de Hallermann-Streiff-François. Thesis, Bordeaux, 1968.

53. Nuyts, J. P , and Bolbart, E. : La dyscéphalie à tête d'oiseau. Syndrome de Hallermann-Streiff-François, Méd. Infant. 75 :425, 1968.

54. Woillez, M , Fontaine, G, Walbaum, R , and Blervacque, A. : Syndrome de Hallermann-Streiff-François. Discussion nosologique à propos de deux cas. Bull. Soc. Opht. Franc. 68 :S94, 1968.

55. Dublineau, P. : Le syndrome de Jules François. Thesis, Angers, 1970.

56. Waardenburg, P. J. : Personal communication. 57. Larmande, A. : Personal communication, 1959. 58. Hallermann, W. : Vogelsicht und C a t a r a c t a

congenita. Klin. Mbl. Augenheilk. 113:315, 1948. 59. Nizetic, B. : Dysmorphic mandibule-faciale et

status dysraphicus. Ophthalmologica 127:1, 1954. 60. Streiff, E. B. : Dysmorphic mandibulo-faciale

(tête d'ooseau) et altérations oculaires. Ophthal-mologica 120:79,1950.

Documents

The François Dyscephalic Syndrome and Skin Manifestations