American Journal of Medical Genetics 46620-622 (1993)

Newly Recognized Blepharofacioskeletal Syndrome A. Richieri-Costa, M.L. Guion-Almeida, E.S.O. Rodini, S.C.S. Pereira, and M.M. Cohen, Jr. Serviqo de Genetica Clinica, Hospital de Pesquisa e Reabilitqcio de Lesdes Lhbw-Palatais, USP, Bauru, SP, Brazil (A.R.-C., M.L.G.-A., E.S.O.R., S.C.S.P.); Department of Oral Biology, Faculty of Dentistry, and Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada (M.M.C. Jr.)

A mother and daughter are described with similar facial and skeletal manifestations. The We have observed an apparently newly recognized syndrome consists Of b1epharophimosis9 syndrome of blepharophimosis, and other facial anoma-

thin lips9 and long lies together with skeletal malformations and deforma- tapering fingers. The facial phenotype changes tions in a mother and child. with age. Autosomal dominant inheritance is suggested. o 1993 WiIey-Lisa, Inc.

KEY WORDS: blepharophimosis, hypotelor- ism, limb anomalies, autoso- The proposita (Figs. 1, 2), who had a striking facial ma1 dominant inheritance, appearance, was seen at age 8 years. She was the prod- changing phenotype uct of a 34-week gestation, delivered by cesarean section

INTRODUCTION

hypoplasiay

CLINICAL REPORT Patient 1

Fig. 1. F’roposita during infancy with blepharophimosis and narrow intercomissural distance. Proposita at age 8 with (a) blepharophimosis and thin lips (b) posteriorly angulated ear Fig. 2.

Received for publication April 20, 1992; revision received De- cember 1, 1992.

Address reprints requests to A. Richieri-Costa ServiFo de Gen6- tica Clinica, Hospital de Pesquisa e FteabilitaClo de Lesdes Labio- Palatais, USP, 17043 Bauru, SP, Brazil.

0 1993 Wiley-Liss, Inc.

Blepharofacioskeletal Syndrome 621

Fig. 3. Hands of proposita showing long tapering fingers and mild clinodactyly.

and weighed 2,760 g (25th centile) at birth with a length of 47 cm (10th centile) and an OFC of 33 cm (50th centile). At age 8 years, height was 120 cm (3rd centile); weight, 21 kg (10th centile); and OFC, 50 cm (50th centile). Intelligence was normal. Blepharophimosis was evident, the inner canthal distance being 2.5 cm (3, < P < 25th centile) and outer canthal distance being 6.8 cm (3rd centile). Other facial findings included upslant- ing palpebral fissures, convergent strabismus, malar hypoplasia, small thin lips, cleft palate, and posteriorly angulated ears. The fingers appeared long and tapering (Fig. 3) with mild clinodactyly of the left 3rd and 4th fingers and the right 2nd and 3rd fingers. The halluces were overlapped by the 2nd toes. Chromosomes were normal.

Fig. 4. Mother during childhood showing similar facial characteris- tics to proposita.

Fig. 5. Mother and daughter.

Patient 2 The mother had an identical facial appearance to that

of her daughter during her own infancy and childhood. The grandmother indicated that her daughter and granddaughter were “hyper alike” during infancy. No photographs of the mother during infancy are available, but a childhood photograph (Fig. 4) shows great sim- ilarity to her daughter. Mother and daughter are shown together in Figure 5. It will be observed that in this syndrome, the facial phenotype changes noticeably from infancy to childhood to adulthood. The mother was 165 cm tall. Intelligence was normal. She had the same ear configuration as that of her daughter but there was no posterior angulation. The palate was intact but the uvula was hypoplastic. The fingers were long and ta- pered with mild clinodactyly of the 3rd and 5th fingers of

TABLE I. Clinical Manifestations

Growth Short stature

Performance Normal

Facial Blepharophimosis Upslanting palpebral fissures Strabismus Malar hypoplasia Small oral aperture Thin lips Cleft palate Posteriorly angulated ears

Long tapered fingers Clinodactyly Congenital hip dislocation Pes valgus

Skeletal

Mother

-

+ + + + + +

a - b -

+ + c

+ -

Child -

-

+ + + + + + + + + + + + d

-

a Mother had hypoplastic uvula. Ears with similar configuration to daughter but not posteriorly angu-

lated. ‘ Left: 3,5. Right 2,3.

Left 3,4. Right 2,3.

622 Richieri-Costa et al.

the left hand and the 2nd and 3rd fingers of the right hand. Bilateral pes valgus during infancy required sur- gical intervention.

DISCUSSION The clinical manifestations in the mother and her

daughter are compared in Table I. We have named this newly recognized condition the blepharofacioskeletal syndrome. Autosomal dominant inheritance is likely. Although the phenotype is more severely manifested in the daughter than in the mother, the syndrome appears to have relatively benign characteristics. However, fur- ther delineation will be necessary to determine the limits of variable expression. Blepharophimosis occurs in several other syndromes, but the overall pattern of anomalies observed in the blepharofacioskeletal syn- drome appears to distinguish it from other syndromes including blepharofacionasal syndrome [Pashayan et al., 19731, frontofacionasal malformation [Gollop, 19811, Marden-Walker syndrome [Jaatoul et al., 19821, and Schwartz-Jampel syndrome [Farrell et al., 19871.

Schilbach and Rott [1988] described a dominantly in- herited syndrome with manifestations similar to our patients. Their patients had ocular hypotelorism, ble-

pharophimosis, upslanting palpebral fissures, and sub- mucous cleft palate. Males had hypospadias. We had no males in our family. Their patients had mild cutaneous syndactyly of the 3rd and 4th fingers and the 2nd and 3rd toes. Some were mentally retarded. Our patients had long tapered fingers, clinodactyly, and normal intel- ligence. In this early stage in the delineation of the blepharofacioskeletal syndrome, it is not possible to say whether Schilbach and Rott’s [19881 family and our family have the same or different syndromes.

REFERENCES Farrell SA, Davidson RG, Thorp P (1987): Neonatal manifestations of

SchwartzJampel syndrome. Am J Med Genet 27:799-805. Gollop TR (1981): Fronto-facio-nasal dysostosis. A new autosomal re-

cessive syndrome. Am J Med Genet 10:409-412. Jaatoul NY, Haddad NE, Khoury LA, Afifi AK, Bahuth NB, Deeb ME,

Mikati MA, Der Kaloustian VM (1982): The Marden-Walker syn- drome. Am J Med Genet 11:259-271.

Pashayan H, Pruzansky S , Putterman A (1973): A family with blepharo-naso-facial malformations. Am J Dis Child 125:389-393.

Schilbach U, Rott H-D (1988): Ocular hypotelorism, submocosal cleft palate, and hypospadias: A new autosomal dominant syndrome. Am J Med Genet 31:863-870.