American Journal of Medical Genetics 47:702-706 (1993)

Mental Retardation, Structural Anomalies of the Central Nervous System, Anophthalmia and Abnormal Nares: A New MCA/MR Syndrome of Unknown Cause

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A. Richieri-Costa and M.L. Guion-Almeida Seruiqo de Genetica Clinica, Hospital de Pesquisa e Reabilitqcio de LesBes Labw-Palatais, Universidade de Scio Paulo, Bauru, SP, Brazil

We report on 2 unrelated Brazilian girls, born to nonconsanguineous parents, and present- ing structural central nervous system defects, hydrocephaly, macrocephaly, craniosynosto- sis, prominent forehead, anophthalmia, and abnormal nares. These patients may have a previously undescribed recurrent-pattern cerebro-oculo-nasal syndrome. 0 1993 Wiley-Liss, Inc.

KEY WORDS: MCA/MR, CNS structural de- fects, anophthalmia, abnor- mal nares, cerebro-oculo- nasal syndrome

INTRODUCTION We have observed a newly recognized syndrome of

structural involvement of the central nervous system, anophthalmia, and abnormal nares in 2 unrelated Bra- zilian girls. Clinical and genetic aspects are discussed.

CLINICAL REPORTS Patient 1

JJMG (Fig. 1A-C), female, born in 1992, was the first child of an 18-year-old G1 white woman and her 26-year- old nonconsanguineous husband. Pregnancy was nor- mal; no toxic, infectious, or traumatic incidents or X-ray exposure were reported. Delivery was at term, through cesarean section. Birth weight (BW) was 3,550 g (50th centile), birth length (TBL) was 50 cm (50th centile), and OFC was not recorded. Craniofacial anomalies and anophthalmia were noted at birth. On clinical examina- tion at age 5 months, weight was 8,470 g (75th centile),

Received for publication May 12,1993; revision received June 9, 1993.

Address reprint requests to A. Richieri-Costa, Serviqo de GenBt- ica Clinica, HPRLLP-USP, P.O. Box 620,17043 Bauru, SP, Brazil.

0 1993 Wiley-Liss, Inc.

height 73 cm (>97th centile), and OFC 53 cm (>97th centile). She had macrocephaly, disjunction of the sagit- tal and metopic sutures, closure of the coronal suture, wide posterior fontanel, asymmetric cranial vault, prominent forehead, frontal encephalocele, flat supra- orbital ridges, sparse and abnormally placed eyebrows, sparse eyelashes, bilateral anophthalmia, an atypical appendage-like structure, hairy in the proximal part, and emerging over the left nostril (Fig. 21, hypoplastic and abnormally modeled “proboscis-like” nares, wide philtrum, “carp-like” mouth, apparently low-set and posteriorly angulated ears, mild malar hypoplasia, and delayed neuropsychological development. There was no evidence of amniotic band-type defects of the limbs.

Results of routine laboratory blood tests were normal. G-banded chromosomes were normal.

CT scan showed frontal encephalocele, right an- ophthalmia, vestigial eye structure on the left, struc- tural anomalies of the central nervous system, and wide ventricular dilatation (Fig. 3A-D).

Patient 2 PC (Fig. 4A-C), female, born in 1987, was the 1st

child of a 22-year-old G1 woman and a noncon- sanguineous man. Pregnancy was normal; no toxic, in- fectious, or traumatic incidents, or X-ray exposure were reported. Delivery was normal and at term. BW was 2,780 g (10th centile), TBL was 49 cm (25th centile), and OFC was not recorded. Anophthalmia and craniofacial anomalies were noted at birth. She was first seen at 43/iz years, with severe malnutrition, and her weight was 5,320 g (<3rd centile), height 78 cm (<3rd centile), and OFC 46.5 cm (50th centile). After 1 year of intensive care the phenotype changed dramatically (Fig. 5A-C).

On clinical examination at age 53/iz, weight was 13 kg (<3rd centile), height 88 cm (<3rd centile), and OFC 49.5 cm (<50th centile). She had prominent forehead, sparse eyebrows, bilateral anophthalmia, abnormally modeled “proboscis-like” left naris, wide philtrum, cleft palate, single maxillary central incisor (Fig. 6), and mental retardation. No amniotic band type defects were found on the limbs.

New Cerebro-Oculo-Nasal MCA/MR Syndrome 703

Fig. 1. (A-C) Clinical aspects of patient 1.

Fig. 2. Clinical aspects of the facial appendage of patient 1.

Routine laboratory blood tests and G-banded chromo- somes were normal.

CT scan showed asymmetric dilatation of the cerebral ventricles, asymmetry of the cerebral hemispheres, atresia of the nasal structures at the left, and calcified remnants of the eye structures (Fig. 7A-D).

DISCUSSION The clinical manifestations in both of these girls are

shown in Table I. We have named this newly recognized condition cerebro-oculo-nasal syndrome. Although the

phenotype in patient 1 is more severe than in patient 2, the clinical signs are quite similar in both, suggesting severely impaired development of the CNS, eye, and midline facial structures. Further delineation will be necessary to determine the limits of phenotypical manifestations, as well as the pattern of inheritance. At the present stage of knowledge it can be considered an unknown-genesis recurrent-pattern MCA/MR syn- drome. Some of the clinical manifestations in the pres- ent patients, taken individually, should be differenti- ated from the clinical signs of other well known

704 Richieri-Costa and Guion-Almeida

Fig. 3. (A-D) CT scan of patient 1.

Fig. 4. (A-C) Clinical aspects of patient 2 at age 43/12 years.

New Cerebro-Oculo-Nasal MCA/MR Syndrome 705

Fig. 5. (A-C) Clinical aspects of patient 2 at age 5% years.

Fig. 6. Clinical aspects of the teeth of patient 2.

TABLE I. Clinical Manifestations

Patient 1 Patient 2

Mental retardation Frontal prominence Hydrocephaly Encephalocele Anophthalmia Abnormal eyebrowsleyela Midline appendage “Proboscis-like” nares Wide philtrum “Carp-like” mouth Cleft palate Single maxillary incisor Abnormal ears CNS structural defects

+ + + + + + + + +

shes +

- ? + +

+ + + + + + + + + + +

-

-

-

706 Richieri-Costa and Guion-Almeida

Fig. 7. (A-D) CT scan of patient 2.

syndromes, including the Delleman syndrome (facial appendages and anophthalmos) [Delleman et al., 1984; Gorlin et al., 1990; Brodsky et al., 19901, the F’raser syndrome (anophthalmos and variable facial anoma- lies) [Ramsing et al., 19901, craniotelencephalic dyspla- sia (protuberance of the frontal bone and delayed neuro- psychomotor retardation) [Jabbour and Taybi, 19641, craniorhiny (craniosynostosis and distinct nasal config- uration) [Mindikoglu et al., 19901, and from the usual holoprosencephalic syndromes [Cohen and Sulik, 19921.

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Gorlin RJ, Cohen MM Jr, Levin LS (1990): “Syndromes of the Head and Neck,” 3rd ed. New York Oxford University Press, pp 511-512.

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