Frontofacionasal dysplasia: Evidence for autosomal recessive inheritance

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  • American Journal of Medical Genetics 19:301-305 (1984)

    Frontofacionasal Dysplasia: Evidence for Autosomal Recessive Inheritance

    T.R. Gollop, M.M. Kiota, R.M.M. Martins, E.A. Lucchesi, and E. Alvarenga Fo

    Servico de Genetica Humana da Associaciio Maternidade de Siio Paulo (7: R. G., M. M. K., R. M. M. M., and .A. L.) and Disciplina de Neurocirurgia of Escola Paulista de Medicina, S3o Paulo, Brazil (E.A. F. ")

    We report on a 2-month-old girl whose parents are first cousins. The patient has severe craniofacial anomalies characterized by: encephalocele, hypertelorism, midface hypoplasia, hypoplasia of frontal bone on the left side, malformed left eye, absent inner eyelashes, irregular S-shaped palpebral fissures, deformed nos- trils, hypoplastic right nasal wing and cleft lip, and clefts of premaxilla, palate and uvula. No other malformations were observed. This association of anomalies suggests the diagnosis of frontofacionasal dysplasia. Parental consanguinity sug- gests autosomal recessive inheritance.

    Key words: frontofacionasal dysplasia, autosomal recessive inheritance


    Frontofacionasal dysostosis was described in two sibs whose parents were first cousins once removed [Gollop, 19811. The following characteristics were noted in these patients: blepharophimosis, lagophthalmos, primary telecanthus, S-shaped pal- pebral fissures, facial hypoplasia, eyelid coloboma, widow's peak, cranium bifidum occultum defect, frontal lipoma, nasal hypoplasia, deformed nostrils, bifid nose, and cleft of lip, premaxilla, palate, and uvula.

    We report here another case of this rare malformation in a child whose parents were first cousins, confirming the existence of this syndrome and its autosomal recessive inheritance.


    The proposita is a 2-month-old girl whose parents are first cousins. Father and mother are 27 and 26 years old, respectively. Pregnancy was uneventful and delivery

    Received for publication October 17, 1983; revision received April 2 , 1984.

    Address reprint request to Dr. Thomaz Rafael Gollop, Rua TabapuB, 649, 4", cj 44 cep. 04533, Sao Paulo, Brazil.

    0 1984 Alan R. Liss, Inc.

  • 302 Gollopetal

    was by cesarean section due to fetal distress. The newborn weighed 2,950 gm and Apgar score was 9 and 10 at 1 and 5 minutes, respectively. The proposita was the first-born live child in her sibship and there were no other prior pregnancies. There is no family history of congenital defects. As far as can be determined, neither parent was exposed to drugs, radiation, or teratogens.

    Physical examination: occipitofrontal circumference (OFC) 40 cm, inner can- thal distance 3.2 cm, outer canthal distance 6.8 cm, canthal index 47, primary telecanthus, hypoplasia of the left frontal bone, cutaneous tag on the left frontal area, microphthalmia, microcornea, cataract. iris coloboma, blepharophimosis, lagophthal- mos and palpebral coloboma on the left side, normal eye on the right side, bilaterally absent inner eyelashes, irregular S-shaped palpebral fissures, down-slanting left palpebral fissure, midface hypoplasia, wide nasal bridge, deformed nostrils, cleft lip, cleft premaxilla, absent middle posterior palate and bifid uvula (Fig. 1). In the left occipital region there was an encephalocele. No malformations of ears, thorax, abdomen, and limbs, and no frontal lipomata were detected. The child is neurologi- cally and psychomotorically normal.

    Roentgenograms showed asymmetry of left orbital and frontal bones, general- ized hypoplasia of facial sinuses, cleft of maxillary bone, and absent middle posterior palate (Fig. 2). Computed tomography of the brain showed asymmetry of lateral ventricles and occipital encephalocele (Fig. 3 ) . Dermatoglyphics were normal.

    Cytogenetics results: The infant had a normal 46,XX chromosome constitution in 11 metaphases stained with conventional techniques and 11 stained by G-banding.

    Fig. I . Facial aspect of' patient with frontofacionasal dysplasia.

  • Frontofacionasal Dysplasia 303

    Fig. 2. Skull roentgenograms (AP).


    The abnormalities described in this patient (whose parents are first cousins) are similar to those reported in the original description of frontofacionasal dysostosis [Gollop, 19811 and are summarized in Table I. We modified this syndromes name because, by definition, the term dysplasia is best applied to this type of malformation than dysostosis.

    In our first patient (case 1, Table I) we noticed a limbic dermoid of the left eye that was not seen in the present case. However, the patient here reported showed a cutaneous tag on the left frontal region. The eye involvement in frontofacionasal dysplasia seems to have great clinical variability. In some cases there is no eye involvement (case 2), other patients (case 1) have minimally affected eyes (ie. a limbic dermoid), and in other cases, as in the present, the eye is severely affected.

    The present infant had encephalocele confirmed by computed tomography of the brain, whereas case 2 had cranium bifidum occultum. We think that both abnor- malities are closely related and this opinion is supported by Cohen [ 19791 in his

  • 304 Gollop et al

    Fig. 3 . Computed tomography of brain showing encephalocele

    TABLE I. Clinical Manifestations Seen in Frontofacionasal Dysplasia in Three Studied Cases

    Case 1 Case 2 Present Manifestations [Gallop, 19811 [Collop. 1981) case ___- Brachycephaly Cranium bifidum occultum Frontal lipoma Widows peak Blepharophirnosis Lagophthalmos Eyelid COlObomd S-shaped palpebral fissures Limbic dermoid of eye Primary telccanthus Nasal hypoplasia Bifid nose Hypoplastic nasal wings Midface hypoplasia Cleft lip Cleft premaxilla Cleft palate Bifid uvula Encephalocele Cataract Absent eyelashes Microphthalmia

    + + -

    + + + + -

    + + ! + + +

    ? + + + + + + + -

    + + ! + + + + + +

    + + + + + + + + + + + +

    Microcornea - - Coloboma of iris - -

  • Frontofacionasal Dysplasia 305

    description of frontonasal dysplasia, which he considered both causally and pathoge- netically heterogeneous. He pointed out that pathogenesis encompasses frontal ence- phalocele, frontal lipoma, frontal teratoma, intrinsic nasal capsule abnormalities, early ossification of the lesser sphenoidal wings, craniosynostosis, and enlargement of the ethmoidal sinuses. The great variety of other anomalies that may occur with frontonasal dysplasia [Gorlin et al, 19761 suggested to Cohen 119791 that several syndromes may be delineated from this group and frontofacionasal dysplasia seems to be one of these syndromes.

    Parental consanguinity in the present case supports autosomal recessive inheri- tance of frontofacionasal dysplasia.

    Differential diagnosis includes the frontonasal dysplasia described by DeMyer [ 19671 characterized by hypertelorism, widows peak, cranium bifidum occultum, primary telecanthus, median cleft of upper lip, median cleft of premaxilla, and median cleft palate. This syndrome may be inherited as an autosomal dominant trait; the majority of cases are sporadic [Gollop, 1981; McKusick, 19831.


    Cohen MM, Jr (1979): Craniofrontonasal dysplasia. BD:OAS XV(5B):85-89. DeMyer W (1967): The median cleft syndrome. Neurology 17:961-971. Gollop TR (198 I ) : Fronto-facio-nasal dysostosis-A new autosomal recessive syndrome. Am J Med

    Gorlin RJ, Pindborg JJ, Cohen MM. Jr (1976): Syndrome of the Head and Neck, Second Ed. New

    McKusick VA (1983): Mendelian Inheritance in Man, Sixth Ed. Baltimore: Johns Hopkins University

    Genet 10:409-412.

    York: McGraw-Hill.


    Edited by John M. Opitz and James F. Reynolds


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