The François Dyscephalic Syndrome and Skin Manifestations

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  • THE F R A N 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 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 headScapho-, 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 anomaliesTeeth absent or malformed, irregularly set with hiatodonty.

    3. Proportioned dwarfism. 4. HypotrichosisParticularly obvious in

    the region of the scalp (alopcie 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 atrophyUsually affecting the skin of the face and especially that of the nose.

    6. Bilateral microphthalmia. 7. Congenital cataractsBilateral, 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 Franois 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 1Miss 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-



    Fig. 1 (Franois and Pierard). Franois' 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 sph .C- 1-50 cyl. ax. at 170. It is 1/10 on the left with sphere 2 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:

    DyscephaliaThe 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.

    OtolaryngologyExamination 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 studiesThese 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 anomaliesThese must have been severe ; the teeth progressively cracked, and between the

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


    Fig. 3 (Franois 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.

    DwarfismThe patient stands 1.57 m and weighs 65 kg.

    HypotrichosisThe 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 alopcie.

    Skin atrophyThe 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 (Franois 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-raysThe 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 developmentThe 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.

    KaryotypeBlood microculture is normal (2n = 46 = 44A + X X ) .

    Histologic examinationWe 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 (Franois 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 a


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