American Journal of Medical Genetics 35:289-290 (1989)
Letter to the Editor Craniosynostosis in the Ullrich-Thrner Syndrome To the Editor: Ullrich-Turner syndrome is a well-known and welldelineated chromosome condition that has been reviewed extensively elsewhere [Gorlin et al., 1990; Hall et al., 19821. It has become apparent that craniosynostosis is a low-frequency abnormality in the Ullrich-Turner syndrome. Five known cases are listedin Table I. Chromosomes were not analyzed in the case of Spence and Havard [1959] because their patient was published in the year Ford et al. [1959] demonstrated that patients with Ullrich-Turner syndrome lacked a sex chromosome. However, the patient’s features were highly suggestive of the diagnosis. In looking a t the sutural involvement of specific cases in Table I, it is clear that any suture can be involved and no suture or sutural combination is characteristic, a t least among the cases noted to date. The pathogenesis is obscure and cannot be related to any known secondary cause of craniosynostosis [Cohen, 19861. Although hyperthyroidism and maternal Graves disease prior to pregnancy have been associated with craniosynostosis [Cohen, 1986,19881, Ullrich-Turner syndrome is associated with a high frequency of autoimmune hypothyroidism and infrequently with acute Hashimoto’s thyroiditis [Hall et al., 1982; Papendieck et al., 19871. Craniosynostosis simply represents one of many known skeletal defects in Ullrich-Turner syndrome. There are three ways to look at how frequently U11rich-Turner syndrome is associated with craniosynostosis. First, Ullrich-Turner syndrome is common enough that early or pronounced craniosynostosis would be obvious. Therefore, it seems reasonable to conclude that clinically observable craniosynostosis is only a n occasional manifestation of the syndrome as the five cases so far seem to indicate. Second, late-onset craniosynostosis after major brain enlargement has taken
place but before cranial sutures normally close is not always a clinically obvious problem. Several roentgencephalometric studies of Ullrich-Turner syndrome [Jensen, 1985; Melosky, 1966; Spiegel et al., 19711have been carried out, but make no mention of craniosynostosis. However, emphasis in these studies was specifically directed to facial measurements without always considering the cranium. Although a confirmatory radiographic study would be useful, we can tentatively conclude that the frequency of less severe, relatively late developing craniosynostosis does not increase the total frequency of craniosynostosis in Ullrich-Turner syndrome. Third, approximately 98-99% of Ullrich-Turner syndrome fetuses are aborted spontaneously [Hall et al., 19821. These can be considered more severely “programmed’ than those that do come to term. Craniosynostosis would not be evident in early abortions. Nevertheless, i t could be speculated that some proportion of these might be “programmed” for craniosynostosis. Since a significant number of patients with UllrichTurner syndrome have minor or even absent rnanifestations, some are diagnosed cytogenetically solely on the basis of short stature. Hall et al. [19821 estimated that one-third of Ullrich-Turner syndrome patients are diagnosed a t birth, one-third during childhood, and onethird during teen-age years when failure to go through puberty becomes evident. The combination of craniosynostosis and short stature in a female patient should suggest cytogenetic study for the possibility of UllrichTurner syndrome. However, the net cast by studying chromosomes on a patient with craniosynostosis is far wider than ruling out Ullrich-Turner syndrome. At present, a t least 23 different aneuploidy conditions have been recorded in association with craniosynostosis [Cohen, 1986,1988J.Thus, chromosome studies are manda-
TABLE I. Cases of Ullrich-Turner Svndrome Associated With Craniosvnostosis Reference Spence and Havard 119591 Bozzala et al. [19861 Massa and VanderschuerenLodeweyckx [19871 Berry et al. [1988] Berry et al. [1988]
Karyotype
Sutures synostosed
Not done 45,x 45,x
Coronal, sagittal Coronal, sagittal Sagittal
45,x 45,X/46,X, + marker
Metopic Coronal, unilateral lambdoidal
~
Received for publication October 6,1988;revision received July 17, 1989. Q
1989 Alan R. Liss, Inc.
290
Cohen
tory in any infant with syndromal craniosynostosis in whom no monogenic or teratogenic syndrome diagnosis can be made. REFERENCES Berry R, Smith ACM, Altshul-Stark M, McBogg P, Hagerman R, Kemper M (1988):Cytogenetic abnormalities in 6 patients with craniosynostosis. Am J Med Genet Suppl 4:188-189 (abstract). Bozzala M, Lorini R, Fiori P, Larizza D, Belufi G (1986):Craniostenose et syndrome de Turner: Association inhabituelle. Ann Pediatr 33:64-66. Cohen MM Jr (1986): “Craniosynostosis: Diagnosis, Evaluation, and Management,” New York: Raven Press. Cohen MM Jr (1988): Craniosynostosis update 1987. Am J Med Genet Suppl 4:99-148. Ford DE, Jones KW, Polani PE, Almeida JL, Briggs J H (1959): A sex chromosomal anomaly in a case of gonadal dysgenesis. Lancet 1~711-713. Gorlin RJ,Cohen MM Jr, Levin LS (1990): “Syndromesofthe Head and Neck,” Ed. 3. New York: Oxford Press. Hall JG, Sybert VP, Williamson RA, Fisher NL, Read SD (1982): Turner’s syndrome. West J Med 137:32-44.
Jensen BL (1985): Craniofacial morphology in Turner syndrome. J Craniofac Genet Dev Biol 5:327-340. Massa G, Vanderschueren-Lodeweyckv M (1987): Turner syndrome and craniosynostosis. Helv Paediatr Acta 42177-180. Melosky LC (1966): A study of dental facial aspects in individuals with X-chromosome aberrations. Master of Science in Dentistry Thesis, University of Washington. Papendieck LG de, Iorcansky S, COCOR, Rivaroln MA, Bergada C (1987):High incidence of thyroid disturbances in 49 children with Turner syndrome. J Pediatr 111:258-261. Spence AW, Havard CWH (1969): Unusual case of gonadal dysgenesis (Turner’s syndrome). Br Med J 2:1288-1291. Spiegel RN, Sather AH, Hayles AB (1971): Cephalometric study of children with various endocrine diseases. Am J Orthodont 59:362-375.
M. Michael Cohen, Jr. Department of Oral Biology, Faculty of Dentistry Department of Pediatrics, Faculty of Medicine Dalhousie University Halifax, Nova Scotia, Canada B3H 355
Letter to the Editor Craniosynostosis in the Ullrich-Thrner Syndrome To the Editor: Ullrich-Turner syndrome is a well-known and welldelineated chromosome condition that has been reviewed extensively elsewhere [Gorlin et al., 1990; Hall et al., 19821. It has become apparent that craniosynostosis is a low-frequency abnormality in the Ullrich-Turner syndrome. Five known cases are listedin Table I. Chromosomes were not analyzed in the case of Spence and Havard [1959] because their patient was published in the year Ford et al. [1959] demonstrated that patients with Ullrich-Turner syndrome lacked a sex chromosome. However, the patient’s features were highly suggestive of the diagnosis. In looking a t the sutural involvement of specific cases in Table I, it is clear that any suture can be involved and no suture or sutural combination is characteristic, a t least among the cases noted to date. The pathogenesis is obscure and cannot be related to any known secondary cause of craniosynostosis [Cohen, 19861. Although hyperthyroidism and maternal Graves disease prior to pregnancy have been associated with craniosynostosis [Cohen, 1986,19881, Ullrich-Turner syndrome is associated with a high frequency of autoimmune hypothyroidism and infrequently with acute Hashimoto’s thyroiditis [Hall et al., 1982; Papendieck et al., 19871. Craniosynostosis simply represents one of many known skeletal defects in Ullrich-Turner syndrome. There are three ways to look at how frequently U11rich-Turner syndrome is associated with craniosynostosis. First, Ullrich-Turner syndrome is common enough that early or pronounced craniosynostosis would be obvious. Therefore, it seems reasonable to conclude that clinically observable craniosynostosis is only a n occasional manifestation of the syndrome as the five cases so far seem to indicate. Second, late-onset craniosynostosis after major brain enlargement has taken
place but before cranial sutures normally close is not always a clinically obvious problem. Several roentgencephalometric studies of Ullrich-Turner syndrome [Jensen, 1985; Melosky, 1966; Spiegel et al., 19711have been carried out, but make no mention of craniosynostosis. However, emphasis in these studies was specifically directed to facial measurements without always considering the cranium. Although a confirmatory radiographic study would be useful, we can tentatively conclude that the frequency of less severe, relatively late developing craniosynostosis does not increase the total frequency of craniosynostosis in Ullrich-Turner syndrome. Third, approximately 98-99% of Ullrich-Turner syndrome fetuses are aborted spontaneously [Hall et al., 19821. These can be considered more severely “programmed’ than those that do come to term. Craniosynostosis would not be evident in early abortions. Nevertheless, i t could be speculated that some proportion of these might be “programmed” for craniosynostosis. Since a significant number of patients with UllrichTurner syndrome have minor or even absent rnanifestations, some are diagnosed cytogenetically solely on the basis of short stature. Hall et al. [19821 estimated that one-third of Ullrich-Turner syndrome patients are diagnosed a t birth, one-third during childhood, and onethird during teen-age years when failure to go through puberty becomes evident. The combination of craniosynostosis and short stature in a female patient should suggest cytogenetic study for the possibility of UllrichTurner syndrome. However, the net cast by studying chromosomes on a patient with craniosynostosis is far wider than ruling out Ullrich-Turner syndrome. At present, a t least 23 different aneuploidy conditions have been recorded in association with craniosynostosis [Cohen, 1986,1988J.Thus, chromosome studies are manda-
TABLE I. Cases of Ullrich-Turner Svndrome Associated With Craniosvnostosis Reference Spence and Havard 119591 Bozzala et al. [19861 Massa and VanderschuerenLodeweyckx [19871 Berry et al. [1988] Berry et al. [1988]
Karyotype
Sutures synostosed
Not done 45,x 45,x
Coronal, sagittal Coronal, sagittal Sagittal
45,x 45,X/46,X, + marker
Metopic Coronal, unilateral lambdoidal
~
Received for publication October 6,1988;revision received July 17, 1989. Q
1989 Alan R. Liss, Inc.
290
Cohen
tory in any infant with syndromal craniosynostosis in whom no monogenic or teratogenic syndrome diagnosis can be made. REFERENCES Berry R, Smith ACM, Altshul-Stark M, McBogg P, Hagerman R, Kemper M (1988):Cytogenetic abnormalities in 6 patients with craniosynostosis. Am J Med Genet Suppl 4:188-189 (abstract). Bozzala M, Lorini R, Fiori P, Larizza D, Belufi G (1986):Craniostenose et syndrome de Turner: Association inhabituelle. Ann Pediatr 33:64-66. Cohen MM Jr (1986): “Craniosynostosis: Diagnosis, Evaluation, and Management,” New York: Raven Press. Cohen MM Jr (1988): Craniosynostosis update 1987. Am J Med Genet Suppl 4:99-148. Ford DE, Jones KW, Polani PE, Almeida JL, Briggs J H (1959): A sex chromosomal anomaly in a case of gonadal dysgenesis. Lancet 1~711-713. Gorlin RJ,Cohen MM Jr, Levin LS (1990): “Syndromesofthe Head and Neck,” Ed. 3. New York: Oxford Press. Hall JG, Sybert VP, Williamson RA, Fisher NL, Read SD (1982): Turner’s syndrome. West J Med 137:32-44.
Jensen BL (1985): Craniofacial morphology in Turner syndrome. J Craniofac Genet Dev Biol 5:327-340. Massa G, Vanderschueren-Lodeweyckv M (1987): Turner syndrome and craniosynostosis. Helv Paediatr Acta 42177-180. Melosky LC (1966): A study of dental facial aspects in individuals with X-chromosome aberrations. Master of Science in Dentistry Thesis, University of Washington. Papendieck LG de, Iorcansky S, COCOR, Rivaroln MA, Bergada C (1987):High incidence of thyroid disturbances in 49 children with Turner syndrome. J Pediatr 111:258-261. Spence AW, Havard CWH (1969): Unusual case of gonadal dysgenesis (Turner’s syndrome). Br Med J 2:1288-1291. Spiegel RN, Sather AH, Hayles AB (1971): Cephalometric study of children with various endocrine diseases. Am J Orthodont 59:362-375.
M. Michael Cohen, Jr. Department of Oral Biology, Faculty of Dentistry Department of Pediatrics, Faculty of Medicine Dalhousie University Halifax, Nova Scotia, Canada B3H 355
