American Journal of Medical Genetics 45534-535 (1993)

Letter to the Editor

Confirmation of the Mandibulofacial Dysostosis, Toriello v p e

To the Editor:

Toriello et al. [1985] have reported on 2 brothers and their maternal first cousin presenting with an appar- ently unique syndrome of microcephaly, downslanting palpebral fissures, low-set protruding ears, bilateral hearing loss, and short stature. The face resembled a mild form of Treacher Collins syndrome. We report on an additional patient with this syndrome.

The propositus, C.M., was the third child of unrelated parents. He was born at term with a birthweight of 3,000 g, length 49 cm, and occipitofrontal circumference (OFC) 34 cm. Mother was 24 years old and the father 22. Family history was unremarkable.

At age 12 months brain stem evoked auditory re- sponses showed a bilateral sensorineural deafness. At 16 years, height was 146 cm (<3rd centile), weight 36 kg (<3rd centile), and OFC 54 cm (<3rd centile). Clinical features were strikingly similar to those outlined in the 3 patients studied by Toriello et al. [19851 (Fig. 1, Table I). Neurological status was normal. Findings on com-

Fig. 1. The patient at age 15 years.

puted tomographic (CT) brain scan, renal echography, and echocardiography were normal. Chromosome anal- ysis yielded a 46,:XY karyotype.

A possible further example of this syndrome has been reported by Kawashima and Tsuji [19871 in a boy and in his presumably heterozygous mother who presented milder manifestations.

TABLE I. Clinical Manifestations of the Mandibulofacial Dysostosis, Toriello Type

General Sex Age (yr) Birthweight (g)

DeveloDment Height Head

Weight Craniofacial

Wangular face Asymmetric face Sparse eyebrows Downslanting

palpebral fissures

Ptosis of upper lids Epicanthal folds Highhroad nasal

Highly arched

Malar hypoplasia Micrognathia Low-setkotated

Mild neck webbing

circumference

bridge

palate

ears

This Toriello et al. r19851 studv

Case 1 Case 2 Case 3 Case 4

M M M M 16 98/12 81/12 10

3,000 2,650 1,900

<5th 10th 10th <3rd <3rd <3rd <3rd <3rd

<3rd ~ 5 t h 5th

+ + + + + +

+ + + + + +

- - - -

+ + + + + + + + + + + + + + + + + + t t v

Visceral - - t + - - - Received for publication February 18, 1992; revision received

Address reprint requests to Leopoldo Zelante, M.D., Servizio di Genetics Medica, Ospedale C.S.S., I.R.C.C.S., 71013 San Giovanni Rotondo FG, Italy.

0 1993 Wiley-Liss, Inc.

Cryptorchidism

pulmonary stenosis

Hearing loss

July 28, 1992. Subvalvar +

+ + + +

Letter to the Editor 535

Toriello et al. [19851 have suggested for this syndrome of branchial arch and other defects an X-linked inheri- tance. The sporadic male patient studied by us does not disagree with the proposed hypothesis.

The confirmation of this branchial arch syndrome cor- roborates the causal heterogeneity of first and second arch defects including mandibulofacial dysostosis (MFD) [Gorlin et al., 19761. In turn it also proves the suggestion of Opitz and Gilbert [1982] that MFD is a developmental field defect, probably due to a neural crest cell deficiency.

REFERENCES Gorlin RJ, Pindborg JJ, Cohen MM (1976): “Syndromes of the Head and

Neck.” New York McGraw Hill, pp 546-562. Kawashima H, Tsuji N (1987): Syndrome of microcephaly, deafness/

malformed ears, mental retardation and peculiar facies in a mother and son. Clin Genet 31:303-307.

Opitz JM, Gilbert EF (1982): CNS anomalies and the midline as a “developmental field.” Am J Med Genet 12:433-455.

Toriello HV, Higgins JV, Abrahamson J, Waterman DF, Moore DW (1985): X-linked syndrome of branchial arch and other defects. Am J Med Genet 21:137-142.

Leopoldo Zelante Lucio Vigliaroli Servizio di Genetica Medica e Divisione ORL Ospedale C.S.S. San Giovanni Rotondo Italy

Rita Mingarelli Bruno Dallapiccola Cattedra di Genetica Umana Universita “Tor Vergata” di Roma Italy