American Journal of Medical Genetics 44800-802 (1992)

Brief Clinical Report

Acro-F’ronto-Facio-Nasal Dysostosis: Report of a New Brazilian Family

A. Richieri-Costa, M.L. Guion-Almeida, and Nina A.B. Pagnan Servko de Gene‘tica Clinica, Hospital de Pesquisa e Reabilitaqio de LesBes Labw-Palatais, Universidade de Scio Paulo, Bauru, SP, Brazil

We report on a Brazilian woman with severe mental retardation, facial and skeletal anom- alies characterized by hypertelorism, eye anomalies, broad notched nasal tip, cleft lip, highly arched palate, camptobrachysyndac- tyly of fingers and toes, and anomalies of the feet. A similarly affected brother died at age one year. The clinical picture strongly sug- gest the diagnosis of the autosomal recessive acro-fronto-facio-nasal dysostosis syndrome (AFFND). Clinical and genetic aspects are dis- cussed. o 1992 wiley-Liss, Inc.

KEY WORDS acro-fronto-facio-nasal dys- ostosis, cleft lip/palate, limb anomalies, mental retarda- tion, autosomal recessive in- heritance

INTRODUCTION The acro-fronto-facio-Nasal (AFFND) syndrome is a

rare autosomal recessive condition manifested by 2 sets of signs related to the facial midline and with multiple skeletal sites [Richieri-Costa et al., 19851. Here we re- port on a Brazilian woman with AFFND syndrome and an equally affected deceased brother. Clinical and ge- netic aspects of this autosomal recessive condition are discussed.

CLINICAL REPORT SMPL (Fig. 1A-C), the proposita, was born in 1965.

She was the second child of a normal 18-year-old G5P3A2 mother and her normal and unrelated 23-year- old husband. Gestation was normal, there was absence of trauma or exposure to toxic or infectious agents. Un- complicated term delivery. BW, TBL, and OFC were not recorded. The outcomes of the other pregnancies re-

Received for publication February 19, 1992; revision received May 19,1992

Address reprint request to A. Richieri-Costa, Servico de GenBt- ica Clinica, Hospital de Pesquisa e Fkabilitaqao de LesBes Lhbio- Palatais, Universidade de S5o Paulo, P.O. Box 620, 17043 Bauru, SP, Brazil.

sulted in 2 first trimester abortions, a normal boy, and an equally affected boy who died at age 1 year. Facial and limbs anomalies were noted at birth.

Examination at age 26 years showed a height of 155 cm (10th centile), weight of 49 kg (50th centile), OFC of 53 cm (50th centile) (both corrected to height), ICD of 3.5 cm (97th centile), OCD of 10.5 cm (>97th centile), right/ left ears 5.5 cm (25th centile). She had mental retarda- tion, brachycephaly, plano-occiput, prominent forehead, low frontal and occipital hairline with a small frontal area with alopecia, hypertelorism, cicatricial ulcera- tions of the corneae? bilateral (polar) cataract, iris atro- phy, markedly at left, “S” shaped palpebral fissures, bilateral ptosis, laterally sparse eyebrows, small ears with prominent helix, hypoplastic lobule and tragus, broad nasal root and notched tip, thin and long face, hypoplasia of the mid-face, surgically corrected left cleft lip, highly arched palate, prominent lower lip, prog- nathism, pectus carinatum, DIP camptodactyly of digits 2 and 5, brachydactyly of digits 1-2-5, hypoplasia of the distal phalanges of digits 1-2-5, broad thumbs, hypo- plasia of fingernails 1-2-5 (Fig. 2), shortness of legs, short and equinovalgus feet, wide gap between toes.1-2, camptosyndactyly of toes 2-3, broad halluces, hypoplas- tic toenails (Fig. 31, and scoliosis.

Roentgenograms showed brachycephaly, obtuse angle of the mandible with prognathism, abnormal relation of the articular surfaces of the carpal bones, short carpus, mainly at left, broad distal phalanges of digit 1, hypo- plastic distal phalanges of digits 2 and 5 (Fig. 41, iliac hypoplasia, markedly at left (Fig. 5), broad and abnor- mally modeled distal tibiofibular epiphyses (Fig. 61, tib- iotalar dislocation, abnormally modeled tarsal bones, metatarsus adductus, broad distal phalanx of toe 1, hy- poplastic distal phalanges of toes 2-5, and lumbar scoliosis.

CT scan showed normal cerebral parenchyma, micro- phthalmia with dense calcification of eye structures at left (Fig. 7A and B).

Results of blood laboratory tests were normal. G-band- ed chromosomes of peripheral lymphocytes were nor- mal. Dermatoglyphic findings are shown in Table I.

DISCUSSION The AFFND is a rare autosomal recessive syndrome;

up to now, only one Brazilian family was reported previ-

0 1992 Wiley-Liss, Inc.

Acro-Fronto-Facio-Nasal Dysostosis 801

Fig. 1. A-C The proposita.

Fig. 2. Hands of the proposita. Fig. 3. Lower limbs of the proposita.

ously [Richieri-Costa et al., 19851. The only differential consideration is the AFFND with genitourinary anoma- lies IRichieri-Costa et al., 19891.

The 2 main sets of anomalies present in the patient here reported involving the facial midline and multiple skeletal sites are rather similar to those previously re- ported in the AFFND syndrome [Richieri-Costa et al., 19851. Different eye anomalies have been reported in

different syndromes within the front0 nasal “dysplasia” spectrum [DeMyer, 1967; Sedano et al., 1970; Kinsey and Streeten, 19771, and it is likely that the eye involve- ment in the present patient is part of the spectrum of this condition. Normal chromosomes, the absence of re- lated abnormalities in relatives, and the recurrence of the condition in sibs support the pattern of autosomal recessive inheritance.

802 Richieri-Costa et al.

TABLE I. Dermatoglyphic Findings

Digits atd angle I1 111 IV V TRC (degrees) ab count bc count cd count ad count ~- - . .- Side I

Right A L' A L" L" 21 53 61 25 36 78 Left L' A L' A A 21 49 43 41 30 109

Fig. 4. Radiograph of the hands of the proposita.

Fig. 7. (A-B) CT scan of the proposita.

Fig. 5 . Radiograph of the pelvis of the proposita.

REFERENCES DeMyer W (1967): The median cleft face syndrome. Neurology 17:

Kinsey JA, Streeten BW (1977): Ocular abnormalities in the median cleft face syndrome. Am J Ophthalmol 83:261-266.

Richieri-Costa A, Colletto GMDD, Gollop TR, Masiero D (1985): A previously undescribed autosomal recessive multiple congenital anomalieslmental retardation (MCNMR) syndrome with fronto- nasal dysostosis, cleft lip/palate, limb hypoplasia, and postaxial poly-syndactyly: Acro-fronto-facio-nasal dysostosis syndrome. Am J Med Genet 20:631-638.

Richieri-Costa A, Montagnoli L, Kamiya TY (1989): Autosomal reces- sive acro-fronto-facio-nasal dysostosis associated with genitouri- nary anomalies. Am J Med Genet 33:121-124.

Sedano HO, Cohen MM, J r , Jirasek J, Gorlin FLJ (1970): Frontonasal dysplasia. J Pediatr 76:906-913.

961-971.

Fig. 6. Drawing of the radiographs of the lower limb of the propo- sita.