American Journal of Medical Genetics 37:227-228 (1990)
Brief Clinical Report ~~~
Ullrich-Turner Syndrome With Agenesis of the Corpus Callosum Masahiko Kimura, Masako Nakajima, and Kunio Yoshino Department of Pediatrics, National Sanatorium Nishi-Tottori Hospital, Tottori-shi, Japan
We report on a 19-year-oldwoman with 45,X Ullrich-Turner syndrome who was severely mentally retarded and had hypotonia. Computer tomography (CT)scan showed agenesis of the corpus callosum. There have been few reports of gross developmental central nervous system (CNS) abnormalities in UllrichTurner syndrome. Only one case of UllrichTurner syndrome with agenesis of the corpus callosum has been reported. The high prenatal lethality of Ullrich-Turnersyndrome may mask a CNS abnormality. KEY
WORDS: Ullrich-Turner syndrome, agenesis of the corpus callosum, CNS abnormality
INTRODUCTION In Ullrich-Turner syndrome, short stature, primary amenorrhea, and multiple minor anomalies are characteristic. Some patients have cardiovascular, renal, and skeletal anomalies. Mental retardation is not a prominent feature and little has been reported on CNS involvement in Ullrich-Turner syndrome [Zellweger et al., 19771.We describe a severely mentally retarded woman with Ullrich-7hrner syndrome and agenesis of the corpus callosum. CLINICAL REPORT This 19-year-old woman was the fourth child of nonconsanguineous parents born a t 38 weeks gestation. Her birthweight was 2,440 g and length was 44.5 cm. She showed poor feeding from birth, and required tube feedings until 6 months. She achieved head control a t 12 months and rolled over a t 30 months. She was nonverbal. She could sit alone, but not walk. There was no history of seizures. She has never had a menstrual period. Her height is 102 cm ( - 11.0 SD; standard deviation) and her weight 18.7 kg ( - 5.0 SD). She had many pigReceived for publication August 7, 1989; revision received February 27, 1990. Address reprint requests to Masahiko Kimura, 876 Mitu Tottori-shi, Japan.
0 1990 Wiley-Liss, Inc.
mented nevi on the face, hypertelorism, downwardslanting eyes, hypoplasia of the medial portions of the eye brows, right exotropia, apparently low-set ears, a highly arched palate, and anteverted nostrils. All teeth were carious and were not useful for biting. Cardiac examination was normal. She had short fingers, cubitus valgus, and inverted feet. Pubic hair was present. Breast development corresponded to Tanner stage I. Dermatographic analysis showed increased numbers of arch on 6 fingers and bilateral distal triradii (t‘ in the left hand and t” in the right hand). Neurological examination showed generalized hypotonia. Fundoscopic examination showed bilateral optic nerve hypoplasia. She could follow a n object with her eyes. She reacted to faint sound. Her mental age was below one year. She was not independent with regard to dressing, eating, and toileting. Chromosome examination of peripheral blood lymphocytes showed a 45,X chromosome constitution. Agenesis of the corpus callosum was shown by brain CT. EEG showed no epileptogenic discharge, but an asymmetry of the background. Intravenous pyelogram demonstrated a right double pelvis and ureter.
DISCUSSION This woman has Ullrich-Turner syndrome and agenesis of the corpus callosum. The cause of agenesis of the corpus callosum is thought to be heterogeneous, but many cases with chromosome aberrations have been reported. Serur et al. [1988] reviewed 100 cases. In all, 21 had a form of trisomy 8, 20 had trisomy 13-15, and 29 had abnormalities of chromosomes 17-18. They concluded that chromosomes 8, 13-15, and 17-18 were important for callosal morphogenesis. There have been very few reports of CNS involvement in Ullrich-Turner syndrome. These anomalies are cortical dysplasia [Brun and Skold, 19681, Dandy-Walker anomaly [Molland and Purcell, 19751, and vein of Galen aneurysms [Jarrel et al., 19811. Only one case with agenesis of the corpus callosum was reported previously [Araki et al., 19871. The case was a 14-year-oldgirl with Ullrich-Turner syndrome, agenesis of the corpus callosum, Hashimoto’s thyroiditis, and horseshoe kidney. She showed short stature and multiple minor anomalies. She was slightly mentally retarded and had no neurological abnormalities, whereas our patient was severely mentally retarded and had hypotonia.
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The prenatal lethality of Ullrich-Turner syndrome is higher than 95% [Carr, 19671. In general spontaneously aborted embryos and fetuses often show CNS malformations [Singh and Carr, 1967; Creasy and Alberman, 19761. To our knowledge, there have been no precise studies of CNS malformations in 45,X abortuses, but there might be the possibility of more CNS anomalies than expected in Ullrich-Turner syndrome.
ACKNOWLEDGMENTS We are grateful to Prof. Kenzo Takeshita, the Divisions of Neuroscience, Tottori University School of Medicine, for his advice in reviewing the manuscript. REFERENCES Araki K, Matumoto K, Shiraishi T, Ogura H, Kurashige T, Kitamura I (1987): Turner svndrome with aeenesis of the comus callosum. Hashimoto thyroiditis and horseushoe kidney. Act; Pediatr Jpn 29:622-626.
Brun A, Skold G (1968): CNS malformation in Turner syndrome. An integral part of the syndrome? Acta Neuropathol 10:159-161. Carr DH (1967): Chromosome anomalies a s a cause of spontaneous abortion. Am J Obstet Gynecol 97:283-293. Creasy MC, Alberman ED (1976): Congenital malformations of the central nervous system in spontaneous abortions. Am J Med Genet 13:9-16. Jarrell HR, Schochet S Jr, Krous H, Barnes P (1981):Turner syndrome and vein of Galen aneurysm-a previously unreported association. Acta Neuropathol (Berl) 55:189-191. Molland EA, Purcell M (1975):Biliary atresia and the Dandy-Walker anomaly in a neonate with 45,X Turner syndrome. J Path01 115:227-330. Serur D, Jeret JS, Winsnieiwski K (1988): Agenesis of the corpus callosum: Clinical, neuroradiological and cytogenetic studies. Neuropediatrics 19237-91, Singh RP, Carr DH (1967): Anatomic findings in human abortions of known chromosome constitution. Obstet Gynecol 29:806-818. Zellweger H, Ionaseseu V, Simpson J , Waziri M, Schochet Jr S (1977): Chromosomal apeuploidies excluding Down syndrome. In Vinken PJ, Brun GW, Myrianthopolos NC (eds): “Congenital Malformations of the Brain and Skull, Part 11.”Amsterdam: Elsevier Science Publishers, Handbook of Clinical Neurology 31(2):495-504.
Brief Clinical Report ~~~
Ullrich-Turner Syndrome With Agenesis of the Corpus Callosum Masahiko Kimura, Masako Nakajima, and Kunio Yoshino Department of Pediatrics, National Sanatorium Nishi-Tottori Hospital, Tottori-shi, Japan
We report on a 19-year-oldwoman with 45,X Ullrich-Turner syndrome who was severely mentally retarded and had hypotonia. Computer tomography (CT)scan showed agenesis of the corpus callosum. There have been few reports of gross developmental central nervous system (CNS) abnormalities in UllrichTurner syndrome. Only one case of UllrichTurner syndrome with agenesis of the corpus callosum has been reported. The high prenatal lethality of Ullrich-Turnersyndrome may mask a CNS abnormality. KEY
WORDS: Ullrich-Turner syndrome, agenesis of the corpus callosum, CNS abnormality
INTRODUCTION In Ullrich-Turner syndrome, short stature, primary amenorrhea, and multiple minor anomalies are characteristic. Some patients have cardiovascular, renal, and skeletal anomalies. Mental retardation is not a prominent feature and little has been reported on CNS involvement in Ullrich-Turner syndrome [Zellweger et al., 19771.We describe a severely mentally retarded woman with Ullrich-7hrner syndrome and agenesis of the corpus callosum. CLINICAL REPORT This 19-year-old woman was the fourth child of nonconsanguineous parents born a t 38 weeks gestation. Her birthweight was 2,440 g and length was 44.5 cm. She showed poor feeding from birth, and required tube feedings until 6 months. She achieved head control a t 12 months and rolled over a t 30 months. She was nonverbal. She could sit alone, but not walk. There was no history of seizures. She has never had a menstrual period. Her height is 102 cm ( - 11.0 SD; standard deviation) and her weight 18.7 kg ( - 5.0 SD). She had many pigReceived for publication August 7, 1989; revision received February 27, 1990. Address reprint requests to Masahiko Kimura, 876 Mitu Tottori-shi, Japan.
0 1990 Wiley-Liss, Inc.
mented nevi on the face, hypertelorism, downwardslanting eyes, hypoplasia of the medial portions of the eye brows, right exotropia, apparently low-set ears, a highly arched palate, and anteverted nostrils. All teeth were carious and were not useful for biting. Cardiac examination was normal. She had short fingers, cubitus valgus, and inverted feet. Pubic hair was present. Breast development corresponded to Tanner stage I. Dermatographic analysis showed increased numbers of arch on 6 fingers and bilateral distal triradii (t‘ in the left hand and t” in the right hand). Neurological examination showed generalized hypotonia. Fundoscopic examination showed bilateral optic nerve hypoplasia. She could follow a n object with her eyes. She reacted to faint sound. Her mental age was below one year. She was not independent with regard to dressing, eating, and toileting. Chromosome examination of peripheral blood lymphocytes showed a 45,X chromosome constitution. Agenesis of the corpus callosum was shown by brain CT. EEG showed no epileptogenic discharge, but an asymmetry of the background. Intravenous pyelogram demonstrated a right double pelvis and ureter.
DISCUSSION This woman has Ullrich-Turner syndrome and agenesis of the corpus callosum. The cause of agenesis of the corpus callosum is thought to be heterogeneous, but many cases with chromosome aberrations have been reported. Serur et al. [1988] reviewed 100 cases. In all, 21 had a form of trisomy 8, 20 had trisomy 13-15, and 29 had abnormalities of chromosomes 17-18. They concluded that chromosomes 8, 13-15, and 17-18 were important for callosal morphogenesis. There have been very few reports of CNS involvement in Ullrich-Turner syndrome. These anomalies are cortical dysplasia [Brun and Skold, 19681, Dandy-Walker anomaly [Molland and Purcell, 19751, and vein of Galen aneurysms [Jarrel et al., 19811. Only one case with agenesis of the corpus callosum was reported previously [Araki et al., 19871. The case was a 14-year-oldgirl with Ullrich-Turner syndrome, agenesis of the corpus callosum, Hashimoto’s thyroiditis, and horseshoe kidney. She showed short stature and multiple minor anomalies. She was slightly mentally retarded and had no neurological abnormalities, whereas our patient was severely mentally retarded and had hypotonia.
228
Kimura et al.
The prenatal lethality of Ullrich-Turner syndrome is higher than 95% [Carr, 19671. In general spontaneously aborted embryos and fetuses often show CNS malformations [Singh and Carr, 1967; Creasy and Alberman, 19761. To our knowledge, there have been no precise studies of CNS malformations in 45,X abortuses, but there might be the possibility of more CNS anomalies than expected in Ullrich-Turner syndrome.
ACKNOWLEDGMENTS We are grateful to Prof. Kenzo Takeshita, the Divisions of Neuroscience, Tottori University School of Medicine, for his advice in reviewing the manuscript. REFERENCES Araki K, Matumoto K, Shiraishi T, Ogura H, Kurashige T, Kitamura I (1987): Turner svndrome with aeenesis of the comus callosum. Hashimoto thyroiditis and horseushoe kidney. Act; Pediatr Jpn 29:622-626.
Brun A, Skold G (1968): CNS malformation in Turner syndrome. An integral part of the syndrome? Acta Neuropathol 10:159-161. Carr DH (1967): Chromosome anomalies a s a cause of spontaneous abortion. Am J Obstet Gynecol 97:283-293. Creasy MC, Alberman ED (1976): Congenital malformations of the central nervous system in spontaneous abortions. Am J Med Genet 13:9-16. Jarrell HR, Schochet S Jr, Krous H, Barnes P (1981):Turner syndrome and vein of Galen aneurysm-a previously unreported association. Acta Neuropathol (Berl) 55:189-191. Molland EA, Purcell M (1975):Biliary atresia and the Dandy-Walker anomaly in a neonate with 45,X Turner syndrome. J Path01 115:227-330. Serur D, Jeret JS, Winsnieiwski K (1988): Agenesis of the corpus callosum: Clinical, neuroradiological and cytogenetic studies. Neuropediatrics 19237-91, Singh RP, Carr DH (1967): Anatomic findings in human abortions of known chromosome constitution. Obstet Gynecol 29:806-818. Zellweger H, Ionaseseu V, Simpson J , Waziri M, Schochet Jr S (1977): Chromosomal apeuploidies excluding Down syndrome. In Vinken PJ, Brun GW, Myrianthopolos NC (eds): “Congenital Malformations of the Brain and Skull, Part 11.”Amsterdam: Elsevier Science Publishers, Handbook of Clinical Neurology 31(2):495-504.
