CLINICAL REPORT

Two Sisters Resembling Gorlin–Chaudhry–MossSyndromeTeresa Aravena,1,2 Crist�obal Passalacqua,1* Oscar Pizarro,3 and Mariana Aracena4

1Hospital Cl�ınico Universidad de Chile, Santiago, Chile2Instituto de Nutrici�on y Tecnolog�ıa de los Alimentos, Universidad de Chile, Santiago, Chile3Hospital Luis Tisne, Santiago, Chile4Hospital Luis Calvo-Mackenna, Santiago, Chile

Received 18 January 2011; Accepted 19 June 2011

The Gorlin–Chaudhry–Moss syndrome (GCMS), was describe

initially by Gorlin et al. [Gorlin et al. (1960)] in two sisters

with craniosynostosis, hypertrichosis, hypoplastic labia

majora, dental defects, eye anomalies, patent ductus arteriosus,

and normal intelligence. Two other sporadic instances have

been documented. Here, we report on two sisters with a

condition with some similarities to GCMS as well as some

differences, which could represent either previously unreported

variability in GCMS, or it may represent a novel disorder.

� 2011 Wiley-Liss, Inc.

Key words: craniosynostosis; hypertrichosis; hypoplastic labia

majora

INTRODUCTION

The Gorlin–Chaudhry–Moss syndrome (GCMS, OMIM 233500)

was described by Gorlin et al. [1960] in two sisters, whose parents

were not consanguineous. Both girls had craniosynostosis,

hypertrichosis, hypoplastic labia majora, dental defects, ocular

anomalies, patent ductus arteriosus, and normal intelligence.

The syndrome name was coined by Cohen [1975]. Ippel et al.

[1992] subsequently published a follow-up studyof the twooriginal

sisters, and also documented two newly recognized sporadic cases

both girls of 4 and 33 years of age, respectively. Here, we report on

two sisters who have a condition with some features with GSM but

other manifestations which have not been previously reported:

cutis aplasia, an ossification defect of the skull, and early mortality.

This condition represents previously unreported variability of

GCMS or it could represent a novel disorder.

CLINICAL REPORTS

The proposita was the fifth child of a nonconsanguineous union of

normal parents. The mother took no medications and was not

exposed to any teratogensduringherpregnancy,whichwasnormal.

Prenatal ultrasound disclosed intrauterine growth retardation

and turricephaly. She was born at term (38 weeks) with growth

deficiency of prenatal onset. Birth weight was 1,740 g (�10th

centile), length was 44 cm (�5th centile), and OFC was 29.5 cm

(�10th centile). At birth, the infant was slightly hypertonic with

turribrachycephaly, hypertrichosis of the scalp and trunk, sincipital

cutis aplasia, low frontal hairline, frontal bossing, midface hypo-

plasia, abnormal external ears, small eyes, downslanting palpebral

fissures, and a narrow, high palate with a submucosa cleft. She also

had a patent ductus arteriosus, umbilical hernia, and hypoplastic

labia majora. Her skin was thin, particularly on the abdomen, and

shehad anumbilical hernia. The patient hadhypoplasia of the distal

phalanges of the fingers and toes, and right-sided cutaneous

syndactyly of the 4th and 5th toes (Figs. 1–3).An echocardiogram demonstrated ventricular enlargement

mild-to-moderate mitral and tricuspid valve regurgitation. Renal

ultrasound at 10 days showed a 9� 7mmcyst in the left kidney and

mild distention of both renal pelves Skull radiographs at 35 days

disclosed a severe ossificationdefect in the parietal andupper half of

the frontal and occipital bones together with a soft tissue increase in

volume of the occipital region. Cerebral ultrasound showed partial

agenesis of the corpus callosum, ventriculomegaly of the anterior

horns, and an underdeveloped cerebellum. The brain scan

demonstrated an ossification defects of the skull with a hypoplastic

appearance of the frontal and parietal bones; widely patent sagittal

*Correspondence to:

Crist�obal Passalacqua, Santos Dumont 999, 5th Floor, Section B,

Independencia, Santiago PC 83800, Chile.

E-mail: cpassalacqua@gmail.com

Published online 9 September 2011 in Wiley Online Library

(wileyonlinelibrary.com).

DOI 10.1002/ajmg.a.34204

How to Cite this Article:Aravena T, Passalacqua C, PizarroO, Aracena

M. 2011. Two sisters resembling

Gorlin–Chaudhry–Moss syndrome.

Am J Med Genet Part A 155:2552–2555.

� 2011 Wiley-Liss, Inc. 2552

and coronal sutures; agenesis of corpus callosum, large ventricles,

and an occipital mass independent of the skull (Figs. 4 and 5). The

patient had persistent respiratory distress, developed pneumonia,

and expired at 5 months of age.

Three male siblings were normal. Her older sister was also

affected with this same syndrome. She had a similar phenotype

with hypertrichosis, midface hypoplasia, low frontal hairline, and

abnormal psychomotor development (Fig. 6). CNS ultrasound at 1

year disclosed asymmetry of the lateral ventricles with prominence

of the right frontal horn and dilatation of the posterior region of the

lateral ventricle; the 3rd and 4th ventricles were normal. The sister

had recurrent episodes of hyperthermia associate with sweating,

while the proposita had profuse sweating episodes without hyper-

thermia. The sister also developed pneumonia and expired at

18 months of age.

The proposita, her sister, and both parents had normal

karyotypes.

FIG. 2. Scalp with sincipital cutis aplasia.

FIG. 3. Left foot at birth. Hypoplastic distal phalanges and 4–5cutaneous syndactyly.

FIG. 1. Turribrachycephaly, hypertrichosis of the scalp and trunk,

facial anomalies, low frontal hairline, frontal bossing, midface

hypoplasia, and small, downslanting palpebral fissures.

FIG. 4. Skull radiographs at 35 days, disclosed a severe ossification

defect in the parietal and the upper half of the frontal and occipital

bones together with a soft tissue increase in volume in the

occipital region.

ARAVENA ET AL. 2553

DISCUSSION

The patient and her sister both had a phenotype with features of the

GCMS and other previously unreported manifestations. Both

sisters had an ossification defect of the skull without craniosynos-

tosis, which has not been recognized previously and may represent

variation in expression of the syndrome ormay characterize a novel

familial disorder.

We have compared our two patients with the four previously

reported cases in Table I. Many similarities between our patients

and the other cases are striking. These include short stature

(growth deficiency of prenatal onset), brachycephaly, midface

hypoplasia, small eyes, downslanting palpebral fissures, epicanthic

folds, hypertrichosis, coarse hair, low frontal hairline, patent ductus

arteriosis, umbilical hernia, and hypoplastic labia majora. Nail

hypoplasia is similar to that in the second patient of Ippel et al.

[1992].

Differences include absent upper eyelid coloboma, lack of hear-

ing loss, and absence of a stocky body build. Some of these features,

such as hearing loss and stocky body build, may be progressive and

occur at a later age. The proposita had cutis aplasia and an occipital

mass in the same zone; post-mortem evaluation suggested that the

occipital mass could be an encephalocele. This rare association was

described by Henriques et al. [2004] in a female newborn with

dysmorphic features not related to GCMS. Both of our patients

had hyperthermia, respiratory distress, pneumonia, and an early

demise, which has not been found in previous cases.

There are similarities betweenourpatients and the second case of

Petty syndrome (OMIM612289) reported byPetty [1990] and later

by Braddock et al. [2010]. Both had short stature, midface hypo-

plasia, nail hypoplasia or aplasia, loose skin, and an early demise,

but they differ by the presence of craniosynostosis, abnormal

vascularity, normal development, and pulmonary hypertension.

Although our patients have some characteristics that are shared

with Petty syndrome, the overall pattern of anomalies in our

patients is more consistent with a diagnosis of GCMS (Table I).

However, one could speculate that GCMS and Petty syndromemay

have common cause or be part of a progeroid spectrum.

All reported cases of GCMS, including our patients, have been

female. Affected sibs have been observed twice [Gorlin et al., 1960;

our two patients]. Cohen [1975] and Gorlin et al. [2001] have

proposed autosomal recessive inheritance. Another possibility is

X-linked dominant inheritance, lethal inmales. Future studies may

possibly shed some light on when molecular basis of the syndrome

becomes known.

Finally, in a report of a female patient by Preis et al. [1995],

Saethre–Chotzen is the most likely diagnosis. They noted some

overlapping features with GCMS. However, hypertrichosis, patent

FIG. 6. Older sister at 15 months of life, showing similar phenotype

(hypertrichosis, midface hypoplasia, low frontal hairline,

downslanting and small palpebral fissures and curves eyebrows).

FIG. 5. CT scan of skull at 41 days showing agenesis of corpus callosum, large ventricles, and an occipital mass (encephalocele?).

2554 AMERICAN JOURNAL OF MEDICAL GENETICS PART A

ductus arteriosis, and hearing loss were absent. Also, their clinical

photograph looks like apatientwithSaethre–Chotzen syndromewith

craniosynostosis of coronal and metopic sutures together with an

ossification defect, which has been reported in some cases of Saethre-

Chotzen syndrome. Surprisingly, the title indicates the opposite

‘‘Gorlin–Chaudhry–Moss or Saethre–Chotzen Syndrome?’’

ACKNOWLEDGMENTS

We are very grateful to Ligia Aranibar and Cristian Garc�ıa for

reinterpreting the tests performed on the patient and toM.Michael

Cohen Jr. for his kindness in reviewing the manuscript andmaking

valuable suggestions about the manuscript.

REFERENCES

Braddock SR, Ardinger HH, Yang CS, Paschal BM, Hall BD. 2010. Pettysyndrome and Fontaine-Farriaux syndrome: Delineation of a singlesyndrome. Am J Med Genet Part A 152:1718–1723.

Cohen MM Jr. 1975. An etiologic and nosologic overview of craniosynos-tosis syndromes. Birth Defects 11:137–189.

Gorlin RJ, Chaudhry AP, Moss ML. 1960. Craniofacial dysostosis,patent ductus arteriosus, hypertrichosis, hypoplasia of labia majora,dental and eye anomalies—A new syndrome? J Pediatr 56:778–785.

Gorlin RJ, Cohen MM Jr, Hennekam RCM. 2001. Syndromes ofthe head and neck, 4th edition. New York: Oxford. pp 664–665 and684–685.

Henriques JG, Pianetti Filho G, Giannetti AV, Henriques KS. 2004. Largescalp and skull defect in patient with aplasia cutis congenital. ArqNeuropsiquiatr 62:1108–1111.

Ippel PF,Gorlin RJ, LenzW, vanDoorne JM, Bijlsma JB. 1992. Craniofacialdysostosis, hypertrichosis, genital hypoplasia, ocular, dental, and digitaldefects: Confirmation of the Gorlin-Chaudhry-Moss syndrome. Am JMed Genet 44:518–522.

Petty M, Laxova R, Wiedemann H. 1990. Previously unrecognized con-genital progeroid disorder. Am J Med Genet 35:383–387.

Preis S, Kaewel EV, Majewski F. 1995. Gorlin-Chaudhry-Moss or Saethre-Chotzen syndrome? Clin Genet 47:267–269.

TABLE I. Comparison of Patients With Gorlin–Chaudhry–Moss Syndrome and Petty Syndrome

Gorlin et al. [1960] Ippel et al. [1992] Patient Aff. sister Petty syndrome

10 yearsa 8 years 4 years 33 years 5 monthsa 18 months 3 months 15 monthsShort stature ND ND — þ þ þ þ þStocky body build þ þ þ/� þ — — — —Brachycephaly þ þ þ þ þ þ þ/� —Midface hypoplasia þ þ þ þ þ þ þ þSmall eyes þ þ þ þ þ þ — þDownslanting palpebral fissures þ þ — þ þ þ þ þColoboma of upper eyelid þ þ þ þ — — — —Narrow palpebral fissures þ þ þ þ þ þ þ þ/�Epicanthic folds þ þ/� — þ — þ — þ/�Small prominent ears þ þ þ þ þ/� þ þ þConductive hearing loss þ þ þ þ — — — —Hypertrichosis þ þ þ þ þ þ þ/� þ/�Coarse hair þ þ þ þ þ þ þ/� —Low frontal hairline þ þ þ þ þ þ — þLimited elbow extension ND ND þ Right — — — —Cutaneous syndactyly — — ND — 4–5 ND 4–5 2–3 and 4–5Nail aplasia or hypoplasia — — — þ þ þ þ þPatent ductus arteriosus þ þ — — þ — þ —Umbilical hernia þ þ — — þ þ þ þHypoplastic labia majora þ þ þ þ þ þ þ NACutis aplasia — — — — þ — — —Early demise — — — — þ þ þ þVascular malformations — — — — — — þ þBlue sclerae — — — — — þ/� þ þLoose skin ND ND ND ND þ þ þ þPulmonary hypertension ND ND ND ND — — þ þScalp hair — — — — — — þ þCraniosynostosis þ þ þ þ — — þ þAff. sister, affected sister; ND, not described; NA, not applicable.aAge of diagnosis.

ARAVENA ET AL. 2555