CLINICAL REPORT

Oral and Dental Abnormalities in Barber–SaySyndromeFabiana Martins, Karem Lopez Ortega, Cybelle Hiraoka, Patricia Ricardo, and Marina Magalh~aes*Department of Oral Pathology, Special Care Dentistry Center, School of Dentistry, University of S~ao Paulo, S~ao Paulo, Brazil

Received 10 November 2008; Accepted 9 March 2009

A previously unreported case of Barber–Say syndrome is de-

scribedwith special attention to dentalmanifestations. A 7-year-

old female with multiple congenital anomalies such mammary

gland hypoplasia, hypertrichosis, ectropion, and redundant skin

was seen at the School ofDentistry of theUniversity of S~aoPaulo.Oral examination revealed macrostomia, broad alveolar ridges,

gingival fibromatosis, taurodontism, delayed tooth eruption,

and malocclusion. Dental treatment included gingivoplasty and

orthodontic treatment. � 2010 Wiley-Liss, Inc.

Key words: Barber–Say syndrome; taurodontism; ectropion;

hypertrichosis; macrostomia

INTRODUCTION

In 1982, Barber et al. described a 31/2-year-old girl with multiple

congenital anomalies such as macrostomia, ectropion, atrophic

skin, hypertrichosis, and growth retardation. The nameBarber–Saysyndrome (BSS, OMIM 209885) was used for the first time by

Martinez-Santana and coworkers in 1993 [Barber et al., 1982;

Martinez-Santana et al., 1993].

The etiology of this rare condition is as yet unclear. Dinulos and

Pagon [1999] suggested an X-linked or autosomal dominant

inheritance, while Martinez-Santana et al. [1993] associated the

syndrome with an autosomal recessive pattern.

Only nine cases have been reported in the scientific literature.

The clinical features of BSS include a ‘‘senile’’ appearance caused by

dry, loose, redundant skin particularly on the forehead, neck and

trunk, as well as in the antecubital and popliteal areas; hypoplasia of

the mammary glands and nipples; hypoplastic genitalia; ectropion;

atrophic skin; hypertrichosis; and growth retardation [Sod et al.,

1997; Mazzanti et al., 1998]. Histopathological analysis of the skin

shows atrophic epidermis with slight orthohyperkeratosis; thin,

reticular dermis; almost complete absence of elastic fibers and

hypocollagenosis [David et al., 1991; Tenea and Jacyk, 2006].

The differential diagnosis of BSS includes ablepharon–macrostomia syndrome (AMS, OMIM 20011). AMS and BBS are

both characterized by macrostomia, hypertelorism, or telecanthus;

abnormal nose and ears; aplasia or hypoplasia of nipples; and

redundancy of the skin. However AMS ablepharon is characterized

by no hair at birth, late development of sparse, thin hair, and total

absence of lanugo [Cesarino et al., 1988;Mazzanti et al., 1998;Tenea

and Jacyk, 2006]. According to Mazzanti et al. [1998] and to

Pellegrino et al. [1996], patients with AMS share many phenotypic

features with BSS patients, suggesting that these disorders may be

allelic. Pelegrinno et al. [1995] demonstrated a complex rearrange-

ment involving chromosome 18, in a BSS patient, and proposed

that the gene(s) for AMS and BSS may lie on chromosome 18.

The craniofacial characteristics of BSS include sparse eyebrows

and eyelashes, ocular hypertelorism or telecanthus, ectropion, low-

set, small andabnormal-shaped ears, bulbousnosewithhypoplastic

nasal alae, thin lips, and hirsutism [Barber et al., 1982]. To our

knowledge, only three studies have reported oral manifestations

such as macrostomia, malocclusion and prognathism [David et al.,

1991; Dinulos and Pagon, 1999], and delayed teeth eruption

[Mazzanti et al., 1998] in patients with BSS.

CLINICAL REPORT

A 7-year-old girl with unremarkable family history was diagnosed

with BSS at birth. She was born of a first-degree consanguineous

marriage after an uncomplicated first full-term pregnancy, to a

28-year-old mother. The patient was referred to the Special Care

Dentistry Center with a complaint of malocclusion and delayed

eruption of most permanent teeth. Physical examination showed

hypoplastic nipples and telangiectases on the chest, severe hyper-

trichosis affecting the back and neck, as well as lanugo covering

the patient’s entire body (Fig. 1). Other features included facial

dysmorphism, low hairline, hypertelorism, eyelid atrophy, sparse

*Correspondence to:

MarinaMagalh~aes, Universidade de S~ao Paulo, Faculdade deOdontologia,

Av. Prof. Lineu Prestes 2227, Departamento de Patologia Bucal, Cidade

Universit�aria-05508-900, S~aoPaulo, SP, Brazil. E-mail:mhcgmaga@usp.br

Published online 9 September 2010 in Wiley Online Library

(wileyonlinelibrary.com)

DOI 10.1002/ajmg.a.32898

How to Cite this Article:Martins F, Ortega KL, Hiraoka C, Ricardo P,

Magalh~aes M. 2010. Oral and dental

abnormalities in Barber–Say syndrome.

Am J Med Genet Part A 152A:2569–2573.

� 2010 Wiley-Liss, Inc. 2569

eyelashes and eyebrows, telecanthus, bulbous nose, hypoplastic

nasal alae, and low-set ears of abnormal shape (Fig. 1).

At oral examination, anomalies of tooth number, tooth size, and

tooth structure were not noticed. The following teeth were present:

all permanent incisors, except for right superior lateral incisor,

two superior deciduous canines, two inferior permanent canines

partially erupted, all deciduousmolars teeth, and all first permanent

molars. Inmaxilla the canines, premolars, and secondmolars germs

were present. Inmandible the pre molars and secondmolars germs

were present.

Regarding tooth shapes anomalies, we observed abnormal cusps

pattern in molars, taurodontic molars, and shovel-shaped upper

incisors.

Dental history revealed delayed tooth eruption, with the first

deciduous tooth erupting at the age of 2. Oral examination revealed

macrostomia, thin upper lip, increased dental arch perimeter, as

well as a hypotonic tongue. The patient presented with anterior

open bite, infraoccludedmolars, overjet, broad alveolar ridges, and

tongue thrust. The crowns of the permanent teeth were partially

covered by gingiva. Less than one third of the clinical crowns of the

upper incisors were visible, and half of the clinical crowns of the

molars were visible (Fig. 2).

Radiographic examination had shown widening of the pulp

cavity of posterior permanent teeth and absence of constriction

in the cementum junction. The first lower permanent molars and

the lower deciduous molar presented an apical displacement of

the roots bifurcation, conferring a rectangular aspect to the pulp

cavities characterizing taurodontism [Constant and Grine, 2001].

Premature apical closure was seen in anterior teeth; the patient was

7 years old and this process should only begin at the age of 9 [Rafter,

2005]. Radiographic examination also revealed atypical incisors

with enhanced marginal ridges and a distinctive shovel-shaped

appearance (Fig. 3).

FIG. 1. Frontal (A) and lateral (B) viewof the patient’s face, forehead

hirsutism, low set and malformed ears, bulbous nose, eyebrows,

and macrostomia were observed. View (C) severe hypertricosis is

observed in back and neck. Thoracic region of the patient from the

front view (D)presenting redundant and thick skin, telangiectasis,

and absence of nipples.

FIG. 2. Intra-oral examination demonstrated macrostomia (A),

partial exposition of the crow of permanent teeth (B), and

morphological alteration of molars (C).

FIG. 3. Panoramic radiography showedmolar taurodontism (A) early

apical closure in permanent anterior teeth (B), shovel-shaped

incisors (C).

2570 AMERICAN JOURNAL OF MEDICAL GENETICS PART A

TABLE

I.OralFindings

inBarber–SayPatients

Maxillofacialmanifestations

Barber

etal.

[1982]

David

etal.

[1991]

Martinez-

Santana

etal.

[1993]

Sod

etal.

[1997]

Mazzanti

etal.

[1998]

Dinulos

andPagon

[1999]

(twocases)

Cort� es

etal.

[2000]

Present

case

Cleftpalate

ND

ND

��

��

��

þHighpalate

þND

ND

þþ

ND

��

ND

Vaultedpalate

þND

ND

þþ

��

��

Mandibularprognathism

ND

þND

þþ

�þ

�þ

Retrognathia

ND

ND

ND

�þ

��

��

Micrognathia

ND

ND

ND

ND

þþ

þ�

þMacrostom

iaND

þþ

þþ

þþ

þþ

Thinupperlip

ND

þþ

þþ

þ�

þþ

Maxillaryhyperdevelopment

(transverse

direction)

ND

ND

ND

ND

ND

ND

ND

þ

ND

Broad

alveolar

ridges

ND

ND

ND

ND

ND

þND

þ�

Abnormalitiesintoothshape

ND

��

ND

ND

ND

ND

þTaurodontism

,shovel-shapedincisor

ND

Hypodontia

ND

ND

ND

ND

þND

ND

�ND

Taurodontism

ND

ND

ND

ND

ND

ND

ND

þND

Increasedenam

eldeposition

ND

ND

ND

ND

ND

ND

ND

þND

Delayed

tootheruption

ND

ND

ND

ND

þND

ND

þND

Prem

atureapicalclosure

ND

ND

ND

ND

ND

ND

ND

þND

Malocclusion

ND

þND

ND

ND

ND

ND

þND

Anterior

open

bite

ND

þND

ND

ND

ND

ND

þND

Macroglossia

ND

þND

ND

ND

ND

ND

�ND

ND,nodata;þ,presence;�,absence.

MARTINS ET AL. 2571

Cephalometric analysis (Ricketts, McNamara, and Jarabak)

showed a skeletal open bite tendency, worsened by the buccal

inclination of the incisors, but still with a harmonious relationship

between the alveolar bone and the chin. Both the length and

inclination of the anterior cranial base were normal (69mm,

9 years old/5� counter-clockwise to The Frankfort Plane). The

maxilla showed normal length and a good position relative to the

cranial base. The mandible showed a slightly posterior position

relative to the cranial base. The body of the mandible was shorter

than normal (55mm), and the length and inclination of the ramus

of the mandible were within the normal range. The transverse

maxillary diameter was disproportionally wide in relation to the

mandibular arch. Anteroposterior dental examination showed that

the patient had Angle Class I malocclusion.

Generalized gingival fibromatosis, partially covering the crowns

of upper and lower anterior teeth, was observed. Gingivectomy

and gingivoplasty were performed, and histological examination

revealed that the mucosa was covered with keratinized stratified

squamous epithelium with rete ridges, and lamina propria com-

posed of fibrous connective tissue with collagen fibers organized in

thick, parallel, irregularly arranged bundles. Abundant collagen

deposition (detected by Masson’s trichrome stain) and absence of

elastic fibers (evidenced byWeigert’s stain using a staining solution

of resorcin and fuchsin) were noticed.

DISCUSSION

This is the first descriptive report of dental and occlusal features of a

patient with BSS (Table I). Themain features of BSS seem to derive

from a developmental abnormality of the skin and adnexa. The

ectodermal structures in our patient, including the teeth, were

impressively compromised, which prompted us to agree with

Martinez-Santana et al. [1993] and Cort�es et al. [2000], who

considered this disorder an ectodermal dysplasia (ED).

There aremore than 150 clinically distinct hereditary syndromes

in which an ED is present. Most syndromes are very rare and

manifest variable defects in morphogenesis of ectodermal struc-

tures, including hair, skin, nails, and teeth [Kere et al., 1996].

Our patient showed several skin and adnexa alterations as laxity

of the skin, absence of mammary glands, and sparse eyelashes and

eyebrows; otherwise, the patient did not have hypondontia or

oligodontia, which is frequent in EDs.

Finally severe hypertrichosis on the back was observed in our

patient and this aspect is not usual in ED.

The main complaint of the patient was the partially erupted

appearance of the permanent teeth. However, radiographic exami-

nation showed complete tooth eruption and premature apical

closure. Clinically, an overgrown gingiva was seen, covering two-

thirds of the clinical crowns. Gingivectomy and gingivoplasty were

performed for crown exposure, and resin was used to restore

vertical dimension in the molars. An orthodontic bracket was then

used to align upper incisors.

Some authors have reported a high vaulted palate in BSS [Sod

et al., 1997; Mazzanti et al., 1998]; our patient, however, presented

with a shallow palate with broad alveolar ridges. Although cepha-

lometric analysis showed a harmonious relationship between

the maxilla and the mandible, our patient exhibited severe facial

dysmorphism, including an anomalously large mouth and

biprotrusion.

As Bloch-Zupan [2007] stated, ‘‘teeth abnormalities are indeed

excellent dysmorphic markers, providing visible evidence, through

their unchanging mineralized state, of earlier developmental ab-

normalities, and giving warning signs that may provide sign-posts

in syndrome diagnosis.’’ In our opinion identification of dental

alterations can be a helpful tool to assess further diagnosis and

dental management of BBS patients.We describe, for the first time,

dental anomalies such as taurodontism, shovel-shaped incisors,

delayed eruption of deciduous dentition, and premature apical

closure.

Histopathological evaluation of the gingival tissue revealed

abundant collagen deposition and absence of elastic fibers. This

pattern has been previously reported in skin biopsies of patients

with BSS [David et al., 1991; Tenea and Jacyk, 2006], and never in

oral mucosa. In skin, it has been associated with laxity. We believe

that the lack of elastic fibers in gingival tissue can cause rigidity of

the gingiva, which consequently becomes an obstacle for completed

tooth eruption.

These developmental disturbancesmay be a helpful tool to assess

further diagnosis and dental management of BBS patients. For this

reason,we encourage authors to analyze these alterations inpatients

with BSS in order to better understand the oral implications of

the syndrome and manners to prevent impaction and dental

malocclusion.

REFERENCES

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

Bloch-Zupan A. 2007. When neuropediatrics meets odontology. Neuro-pediatrics 38:57–58.

Cesarino EJ, Pinheiro M, Freire-Maia N, Meira-Silva MC. 1988.Lid agenesis-macrostomia-psychomotor retardation-forehead hyper-trichosis–A new syndrome? Am J Med Genet 31:299–304.

Constant DA, Grine FE. 2001. A review of taurodontism with new data onindigenous southern African populations. Arch Oral Biol 46:1021–1029.

Cort�es FM, Troncoso LA, Alliende AR, Curotto BL. 2000. Barber-Saysyndrome: Further delineation of the clinical spectrum. Genet Mol Biol23:265–267.

David A, Gordeeff A, Badoual J, Delaire J. 1991. Macrostomia, ectropion,atrophic skin, hypertrichosis: Another observation. Am J Med GenetSuppl 39:112–115.

Dinulos MB, Pagon RA. 1999. Autosomal dominant inheritance of Bar-ber–Say syndrome. Am J Med Genet 86:54–56.

Kere J, Srivastava AK, Montonen O, Zonana J, Thomas N, Ferguson B,Munoz F, Morgan D, Clarke A, Baybayan P, Chen EY, Ezer S, Saarialho-Kere U, de la Chapelle A, Schlessinger D. 1996. X-linked anhidrotic(hypohidrotic) ectodermal dysplasia is caused by mutation in a noveltransmembrane protein. Nat Genet 13:409–416.

Martinez Santana S, Alvarez FP, Frias JL, Mart�ınez-Fr�ıas ML. 1993.Hypertrichosis, atrophic skin, ectropion, macrostomia (Barber–Saysyndrome): Report of a new case. Am J Med Genet 47:20–23.

2572 AMERICAN JOURNAL OF MEDICAL GENETICS PART A

Mazzanti L, Bergamaschi R, Neri I, Perri A, Patrizi A, Cacciari E, ForaboscoA. 1998. Barber–Say syndrome: Report of a new case. Am J Med Genet78:188–191.

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 laxa: Possible localization to 18q.Hum Genet 97:532–536.

Rafter M. 2005. Apexification: A review. Dent Traumatol 21:1–8.

Sod R, Izbizky G, Cohen-Salama M. 1997. Macrostomia, hypertelorism,atrophic skin, severe hypertrichosis without ectropion: Milder form ofBarber–Say syndrome. Am J Med Genet 73:366–367.

Tenea D, Jacyk WK. 2006. What syndrome is this? Pediatr Dermatol23:183–184.

MARTINS ET AL. 2573