Ablepharon-Macrostomia syndrome: First report of familial occurrence

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Ablepharon-Macrostomia Syndrome: First Report of Familial Occurrence Victor E.F. Ferraz , 1 * De ´ bora G. Melo, 1 Susanne E. Hansing , 1 Antonio A.V. Cruz , 2 and Joa ˜ o M. Pina-Neto 1 1 Department of Genetics, Faculty of Medicine of Ribeira ˜ o Preto, University of Sa ˜ o Paulo, Ribeira ˜ o Preto, SP, Brazil 2 Department of Ophthalmology, Faculty of Medicine of Ribeira ˜ o Preto, University of Sa ˜ o Paulo, Ribeira ˜ o Preto, SP, Brazil Ablepharon-macrostomia syndrome (AMS) is a rare condition comprising severe defi- ciency of the anterior lamella of both eye- lids, abnormal ears, macrostomia, anoma- lous genitalia, redundant skin, and absence of lanugo. There is no agreement about cause; some authors suggest autosomal re- cessive inheritance. We describe familial oc- currence of AMS in a girl, sister of a previ- ously reported patient. The father has facial anomalies that suggest autosomal dominant inheritance. Am. J. Med. Genet. 94:281–283, 2000. © 2000 Wiley-Liss, Inc. KEY WORDS: ablepharon-macrostomia syndrome; partial lid agen- esis; autosomal dominant in- heritance; familial occur- rence INTRODUCTION The ablepharon-macrostomia syndrome (AMS) was first reported by McCarthy and West [1977] and com- prises absence of eyelids, macrostomia, malformed ears, redundant skin, absence of lanugo, and ambigu- ous genitalia. To our knowledge only 7 cases have been reported, 5 males and 2 females [McCarthy and West, 1977; Hornblass and Reifler, 1985; Price et al., 1991; Markouizos et al., 1990; Cruz et al., 1995; Pellegrino et al., 1996]. All cases were sporadic. We describe a new case of this syndrome, the first recurrence known, sis- ter of an affected child described by Cruz et al. [1995]. CLINICAL REPORT The patient (Fig. 1) is the third child of a 23-year-old mother with a nonconsanguineous 25-year-old father, whose first child, a girl now 5 years old [Cruz et al., 1995], was diagnosed as having AMS at birth. During pregnancy an omphalocele was detected ultrasono- graphically; amniocentesis was performed and the karyotype was 46,XX. The child, a girl born at term, weighed 3,050 g. Soon after, it was noted that the girl had several anomalies, including severe shortness of the eyelids, a low nasal bridge with hypoplastic and anteverted nostrils, macrostomia, small and abnor- mally modeled ears, absence of nipples, a 6-cm ompha- locele, anteriorly located anus, hypoplasia of labia ma- jor, hypoplastic nails, distal attenuation of phalanges, redundant skin, and absence of lanugo. A diagnosis of AMS was made. Omphalocele and eyelids were re- paired with good results. The father (Fig. 2) of the chil- dren had a small coloboma on the right superior eyelid, irregularities and lack of cilia on the palpebral mar- gins, rarefaction of the body and lateral portion of the eyebrows, and short posteriorly angulated ears. He de- nied any previous trauma or surgery that could explain the palpebral findings. The mother and the second child were normal, and no other relatives were said to have similar anomalies. Chromosomes of the parents were normal. The older daughter (Fig. 3) with AMS is now 5 years old and has had several oculoplastic operations to cor- rect the eyelids and later complications such as lower and upper cicatricial ectropion. Presently her height is 108 cm (50th centile), weight 17,850 g (25th centile) and OFC 51 cm (50th centile). The head is normal in shape, but scalp hair is sparse. She also had apparently hypertelorism, low-set, cup-shaped ears with simple helices, a broad nasal root, anteverted nares with grooving of the alar wings, macrostomia with displaced lateral corners of the mouth, webbed fingers, redun- dant skin, and hypoplastic nipples and labia. The karyotype performed at a 550 band level was normal (46,XX). DISCUSSION To our knowledge, this is the first report of familial occurrence of the AMS. This condition is similar in some aspects (macrostomia, hypertelorism, abnormal nose and ears; aplasia or hypoplasia of nipples; redun- dant skin) to the Barber-Say syndrome (BSS) [Barber *Correspondence to: Victor E.F. Ferraz, Departamento de Ge- ne ´tica, FMRP-USP, Ribeira ˜ o Preto, SP, Brasil 14049-900. Received 1 November 1999; Accepted 2 May 2000 American Journal of Medical Genetics 94:281–283 (2000) © 2000 Wiley-Liss, Inc.

Transcript of Ablepharon-Macrostomia syndrome: First report of familial occurrence

Page 1: Ablepharon-Macrostomia syndrome: First report of familial occurrence

Ablepharon-Macrostomia Syndrome: First Report ofFamilial Occurrence

Victor E.F. Ferraz ,1* Debora G. Melo,1 Susanne E. Hansing ,1 Antonio A.V. Cruz ,2 andJoao M. Pina-Neto 1

1Department of Genetics, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil2Department of Ophthalmology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto,SP, Brazil

Ablepharon-macrostomia syndrome (AMS)is a rare condition comprising severe defi-ciency of the anterior lamella of both eye-lids, abnormal ears, macrostomia, anoma-lous genitalia, redundant skin, and absenceof lanugo. There is no agreement aboutcause; some authors suggest autosomal re-cessive inheritance. We describe familial oc-currence of AMS in a girl, sister of a previ-ously reported patient. The father has facialanomalies that suggest autosomal dominantinheritance. Am. J. Med. Genet. 94:281–283,2000. © 2000 Wiley-Liss, Inc.

KEY WORDS: ablepharon-macrostomiasyndrome; partial lid agen-esis; autosomal dominant in-heritance; familial occur-rence

INTRODUCTION

The ablepharon-macrostomia syndrome (AMS) wasfirst reported by McCarthy and West [1977] and com-prises absence of eyelids, macrostomia, malformedears, redundant skin, absence of lanugo, and ambigu-ous genitalia. To our knowledge only 7 cases have beenreported, 5 males and 2 females [McCarthy and West,1977; Hornblass and Reifler, 1985; Price et al., 1991;Markouizos et al., 1990; Cruz et al., 1995; Pellegrino etal., 1996]. All cases were sporadic. We describe a newcase of this syndrome, the first recurrence known, sis-ter of an affected child described by Cruz et al. [1995].

CLINICAL REPORT

The patient (Fig. 1) is the third child of a 23-year-oldmother with a nonconsanguineous 25-year-old father,whose first child, a girl now 5 years old [Cruz et al.,

1995], was diagnosed as having AMS at birth. Duringpregnancy an omphalocele was detected ultrasono-graphically; amniocentesis was performed and thekaryotype was 46,XX. The child, a girl born at term,weighed 3,050 g. Soon after, it was noted that the girlhad several anomalies, including severe shortness ofthe eyelids, a low nasal bridge with hypoplastic andanteverted nostrils, macrostomia, small and abnor-mally modeled ears, absence of nipples, a 6-cm ompha-locele, anteriorly located anus, hypoplasia of labia ma-jor, hypoplastic nails, distal attenuation of phalanges,redundant skin, and absence of lanugo. A diagnosis ofAMS was made. Omphalocele and eyelids were re-paired with good results. The father (Fig. 2) of the chil-dren had a small coloboma on the right superior eyelid,irregularities and lack of cilia on the palpebral mar-gins, rarefaction of the body and lateral portion of theeyebrows, and short posteriorly angulated ears. He de-nied any previous trauma or surgery that could explainthe palpebral findings. The mother and the secondchild were normal, and no other relatives were said tohave similar anomalies. Chromosomes of the parentswere normal.

The older daughter (Fig. 3) with AMS is now 5 yearsold and has had several oculoplastic operations to cor-rect the eyelids and later complications such as lowerand upper cicatricial ectropion. Presently her height is108 cm (50th centile), weight 17,850 g (25th centile)and OFC 51 cm (50th centile). The head is normal inshape, but scalp hair is sparse. She also had apparentlyhypertelorism, low-set, cup-shaped ears with simplehelices, a broad nasal root, anteverted nares withgrooving of the alar wings, macrostomia with displacedlateral corners of the mouth, webbed fingers, redun-dant skin, and hypoplastic nipples and labia. Thekaryotype performed at a 550 band level was normal(46,XX).

DISCUSSION

To our knowledge, this is the first report of familialoccurrence of the AMS. This condition is similar insome aspects (macrostomia, hypertelorism, abnormalnose and ears; aplasia or hypoplasia of nipples; redun-dant skin) to the Barber-Say syndrome (BSS) [Barber

*Correspondence to: Victor E.F. Ferraz, Departamento de Ge-netica, FMRP-USP, Ribeirao Preto, SP, Brasil 14049-900.

Received 1 November 1999; Accepted 2 May 2000

American Journal of Medical Genetics 94:281–283 (2000)

© 2000 Wiley-Liss, Inc.

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et al., 1982; David et al., 1991; Martinez-Santana et al.,1993], but both have distinguishing manifestations(“ablepharon,” absence of lanugo and hair at birth, andlate development of sparse and thin hair in AMS; ec-tropion and hypertrichosis in BBS) [Mazzanti et al.,1998]. Cesarino et al. [1998] described a patient withlid agenesis, macrostomia, psichomotor retardation,and forehead hypertrichosis and suggested that itshould be classified as a subgroup of Freire-Maia’s clas-sification of the ectodermal dysplasias and that thisshould be done for all cases of AMS and BBS. We agreewith him and also with Mazzanti et al. [1998] who sug-gests that AMS and BBS are different entities thatmay result from mutation or defective regulation of thesame gene. Recently, Dinugo and Pagon [1999] re-ported on a mother-to-son transmission of Barber-Saysyndrome, suggesting an autosomal dominant disor-der.

It has been proposed that AMS is an autosomal re-cessive trait because of the case reported by Azevedo etal. [1973] of children with cryptophthalmos and palpe-bral agenesis born to normal and consanguineous par-ents. The patient related by Azevedo et al. [1973] hadforehead skin directly attached to the esclera. We thinkthat the “agenesis” in this case could in fact be anaborted cryptophthalmos, characterized by the lack ofeyelids, replaced by skin that passes over the orbitalmargins, in continuity with the cheek and forehead.Fibrous tissue adherent to the skin replaces the cornea,and the conjunctiva does not exist. Cruz et al. [1995]indicated that AMS patients have a different ophthal-mologic condition, characterized by short anterior la-mella of the eyelids, with no other abnormalities asexpected in aborted cryptophthalmos.

All cases of AMS previously described were sporadic.The recurrence reported here strongly suggests mono-genic inheritance. Palpebral and auricular anomaliesin the father of the patients seem to be mild expres-sions of some of the anomalies present in the childrensuggesting, in this family, autosomal dominant inher-

itance with variable expression. However, an autoso-mal recessive trait cannot be excluded.

Pellegrino et al. [1996] reported cutis laxa and someAMS findings in a patient with a deletion/inversion ofthe long arm of chromosome 18, suggesting that thegene responsible for the AMS is located on this chro-mosome. Molecular studies involving chromosome 18markers should be the next step for the AMS family

Fig. 1. A: Patient at birth. B,C: With 3 months of age, after corrective surgeries for the omphalocele and the eyelid anomaly.

Fig. 2. A,B: The father of the children. C,D: Note the eyelid, palpebral,and eyebrow anomalies.

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described here, and, ideally, for the BBS family de-scribed by Dinugo and Pagon [1999].

ACKNOWLEDGMENTS

We thank the Service of Photography, the Labora-tory of Cytogenetics, and the Departments of Pediatricsand Plastic Surgery of the Faculdade de Medicina deRibeirao Preto, University of Sao Paulo for clinical andscientific support, and Dr. David de Jong and Dr. Be-atriz R. Versiani for linguistic assistance.

REFERENCES

Azevedo ES, Biondi J, Ramalho LM. 1973. Cryptophthalmos in two fami-lies from Bahia, Brazil. J Med Genet 10:389–392.

Barber N, Say B, Bell RF, Merveille OC. 1982. Macrostomia, ectropion,atrophic skin, hypertrichosis and growth retardation. Synd Ident 8:6–9.

Cesarino EJ, Pinheiro M, Freire-Maia N, Meira-Silva MC. 1988. Lid agen-esis-macrostomia-psychomotor retardation-forehead hypertrichosis: anew syndrome? Am J Med Genet 31:299–304.

Cruz AAV, Guimaraes FC, Obeid HN, Ferraz VEF, Noce TR. 1995. Con-genital shortening of the anterior lamella of all eyelids: the so-called

ablepharon macrostomia syndrome. Ophthal Plast Reconstr Surg 11:284–287.

David A, Gordeeff A, Badoual J, Delaire J. 1991. Macrostomia, ectropion,atrophic skin, hypertrichosis: another observation. Am J Med Genet39:112–115.

Dinugo MB, Pagon RA. 1999. Autosomal dominant inheritance of Barber-Say syndrome. Am J Med Genet 86:54–6.

Hornblass A, Reifler DM. 1985. Ablepharon macrostomia syndrome. Am JOphthalmol 99:552–556.

Markouizos D, Siddiqi U, Siddiqi S, Raziuddin K, Nangia B. 1990.Ablepharon macrostomia syndrome: report of a case and clinical delin-eation (Abstract). Am J Hum Genet 47(Suppl.):A66.

McCarthy GT, West CM. 1977. Ablepharon macrostomia syndrome. DevMed Child Neurol 19:659–672.

Martinez-Santana S, Perez-Alvarez F, Frıas JL, Martınez-Frias M-L. 1993.Hypertrichosis, atrophic skin, ectropion, and macrostomia (Barber-Saysyndrome): report of a new case. Am J Med Genet 47:47–20.

Mazzanti L, Bergasmachi R, Neri I, Perri A, Patrizi A, Cacciari E,Forabosco A. 1998. Barber-Say syndrome: report of a new case. Am JMed Genet 78:188–191.

Pellegrino JE, Schnur RE, Boghosian-Sell L, Strathdee G, Overhauser J,Spinner NB, Stump T, Grace K, Zackai EH. 1996. Ablepharon macro-stomia syndrome with associated cutis laxia: possible localization to18q. Hum Genet 97:532–536.

Price NJ, Pugh RE, Farndon PA, Willshaw HE. 1991. Ablepharon macro-stomia syndrome. Br J Ophthalmol 75:317–319.

Fig. 3. A: The oldest daughter at birth. B,C: The same child at 5 years old.

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