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Genetics and Molecular Biology

Print version ISSN 1415-4757On-line version ISSN 1678-4685

Genet. Mol. Biol. vol. 21 n. 4 São Paulo Dec. 1998 


Say syndrome: A new Brazilian case


M.L. Guion-Almeida, N.M. Kokitsu-Nakata and R.M. Zechi
Serviço de Genética Clínica, Hospital de Pesquisa e Reabilitação de Lesões Lábio-Palatais, Universidade de São Paulo, Caixa Postal 620, 17043-900 Bauru, SP, Brasil. Fax: (014) 234.7818. Send correspondence to M.L.G.-A.




We report on a Brazilian boy, born to nonconsanguineous parents, who presented short stature, microcephaly, large ears, Robin sequence, hand anomalies, delayed bone age, and developmental delay. Major signs found in this patient are related to the Say syndrome.




Say syndrome is characterized by a distinct pattern of anomalies, including cleft palate, microcephaly, large ears, and short stature, apparently inherited in an autosomal dominant fashion. This syndrome was first described in four members from three generations of a family, by Say et al. (1975). Digital anomalies, hypospadia, hypotonia, and developmental delay were also observed. Subsequently, two new cases presenting most of the original features of the Say syndrome were reported (Abu-Libdeh et al., 1993; Ashton-Prolla and Félix, 1997). Cystic renal dysplasia was an additional finding observed in both cases.



J.N.M.L. was a boy born after 38 weeks of gestation to a normal 18-year-old mother and a normal 15-year-old-father after an uncomplicated pregnancy. There was no parental consanguinity.

At birth, the infant presented microcephaly, large ears, cleft palate, micrognathia, glossoptosis, birth weight 2,950 g (10th percentile), length 48 cm (10th percentile), and occipitofrontal circumference (OFC) of 32 cm (2nd percentile).

On physical examination at nine months (Figure 1), the infant's weight was 8.0 kg (3rd percentile); length was 65 cm (3rd percentile), and OFC was 40 cm (<2nd percentile). A high forehead, large ears, high root nose, prominent eyes, and micrognathia gave him an unusual facial appearance that improved with age (Figures 1 and 2). Generalized hypotonia was present with moderate developmental delay. At the age of 18 months he developed seizures. At age 3 7/12 years, he measured 92 cm (3rd percentile) and his OFC was 44 cm (<2nd percentile). In addition, he had a small round face, prominent antihelix, poorly formed antitragus, proximally placed thumbs, clinodactyly of the fifth fingers, and hypoplastic toe nails (Figure 3). He walked and started speaking (two to three words) when he was three years old.


21n4a7f1.GIF (11553 bytes)

Figure 1 - Clinical aspects of the patient at nine months.



21n4a7f2.GIF (13982 bytes)

Figure 2 - Clinical aspects of the patient at five years.



21n4a7f3.GIF (8615 bytes)

Figure 3 - Clinical aspects of the hands of the patient.


Cranial computed tomography showed mild cerebral cortical atrophy and mild enlargement of lateral ventricles. Chromosome analysis performed on cultured leukocytes was normal (46,XY). Other diagnostic evaluations included a negative TORCH screen, normal routine blood and immunological studies, and normal fundoscopy. Radiographs of the hands at five years (Figure 4) showed hypoplastic distal phalanges and delayed bone age (3 1/2 years by Greulich-Pile criteria). Renal ultrasonographic evaluation was normal.


21n4a7f4.GIF (13381 bytes)

Figure 4 - Radiological aspects of the hands of the patient at five years.



The proband described here had cleft palate, microcephaly, large ears, and short stature, which are the main clinical findings of Say syndrome (McKusick catalog number 181180, McKusick 1994). In 1993, Abu-Libdeh et al. reported a case with important signs of Say syndrome: digital anomalies (which were seen in some of the affected members of the original family), retarded bone age, developmental delay, and proximal renal tubular acidosis associated with cystic renal dysplasia. This additional finding was also observed in the third report of Say syndrome (Ashton-Prolla and Félix, 1997). These authors described monozygotic twins, discordant for this condition, and proposed a post-zygotic mutation as the cause of this autosomal dominant syndrome.

Our patient presented most of the characteristics initially described by Say et al. (1975), though cystic renal dysplasia was not observed. Glossoptosis, seizures, and cerebral anomalies, signs present in our case, were not observed in previous reports of Say syndrome. It is possible that they may have occurred by chance, or they may represent a more affected phenotype. The clinical signs in this patient were different from the clinical signs of other known syndromes. When we compare the clinical signs of the present patient (considering microcephaly, cleft palate, and large ears as mandatory signs) with other syndromes in the LDDB and MIM program, we have as differential diagnosis the following conditions: Kabuki make-up syndrome, Braddock-Carey syndrome, Christian syndrome, Hunter syndrome, oculo-palato-cerebral dwarfism syndrome, and Gillessen-Kaesbach syndrome. However, the distinctive facial appearance, the clinical signs, and the laboratory studies of our patient ruled out the above conditions.

In conclusion, our patient appears to represent a new isolated case of Say syndrome, probably originated by a new mutational event. Additional case reports are required to define the full phenotypic spectrum of this condition.



Publication supported by FAPESP.




Os autores descrevem um menino, filho de pais normais e não-consanguíneos, apresentando baixa estatura, microcefalia, orelhas grandes, seqüência de Robin, anomalias digitais, atraso na idade óssea e atraso no desenvolvimento neuropsicomotor. Estudo cromossômico mostrou cariótipo normal, 46,XY. Os achados são compatíveis com a síndrome de Say.




Abu-Libdeh, B., Fujimoto, A. and Ehinger, M. (1993). Syndrome of cleft palate, microcephaly, large ears, and short stature (Say syndrome). Am. J. Med. Genet. 45: 358-360.         [ Links ]

Ashton-Prolla, P. and Félix, T.M. (1997). Say syndrome: A new case with cystic renal dysplasia in discordant monozygotic twins. Am. J. Med. Genet. 70: 353-356.         [ Links ]

Baraitser, M. and Winter, R.M. (1996). LDDB: London Dysmorphology Database. Oxford University Press, London.         [ Links ]

McKusick, V.A. (1994). "Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders". 11th edn. The Johns Hopkins University Press, Baltimore and London.         [ Links ]

MIM-CD: Mendelian inheritance in man (CD-ROM) (1997). The Johns Hopkins University, Baltimore.         [ Links ]

Say, B., Barber, D.H., Hobbs, J. and Coldwell, J.G. (1975). A new dominantly inherited syndrome of cleft palate. Humangenetik 26: 267-269.         [ Links ]


(Received November 10, 1997)

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