Acta Pzdiatr Scand 65: 387-389. 1976
CASE REPORT
FAMILIAL OCCURRENCE OF CEREBRAL GIGANTISM, SOTOS’ SYNDROME F. J U U L HANSEN and BIRGITTE FRIIS From the Department of Puediatrics, Rigshospitulet, Blegdamsvej, Copenhugen, Denmurk
ABSTRACT. Juul Hansen, F. and Friis, B. (Department of pediatrics, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark). Familial Occurrence of cerebral gigantism, Sotos’ syndrome. Acta Paediatr Scand, 65: 387, 1976.Eince the original description of cerebral gigantism, about 85 cnses have been reported. Four papers comment on familial occurrence but never in parents and their children. This paper describes the syndrome in a mother and her child, which, together with facts pointing towards prenatal etiology, such as excessive birthweight, striking mutual resemblance and abnormal dermatoglyphics, points to a genetic defect. Previous endocrine studies are enlarged by the findings of normal serum somatomedin and serum prolactin.
KEY WORDS: Cerebral gigantism, familial Occurrence, somatomedin, prolactin
In 1964 Sotos and associates (14) described the syndrome of cerebral gigantism, consisting of a nonprogressive neurological disorder, mental deficiency, cranio-facial dysmorphology, accelerated infantile growth with acromegalic characteristics and advanced skeletal maturation without endocrinological abnormalities. Some 85 cases have been reported. It has been assumed that the condition is caused by a diencephalic lesion, but the etiology and pathophysiology have not been elucidated. The symptom complex is, however, generally recognized as a distinct entity (3, 4), which can easily be separated from other diencephalic syndromes. Familial occurrence has been described in four papers (2, 5 , 6, 13) but never in parents and their children. We therefore wish to report a case of cerebral gigantism in a mother and her son, as a contribution to the discussion of etiology of the syndrome. CASEREPORTS Mother No. 9/11. Eight of her brothers and sisters have children, all of normal height. No neurologic or endocrine disease 25-762813
was present in the family. Birthweight 6000 g. She was always taller than children of the same age. She started school at the age of 7 years and eventually managed normal school. At the age of 9 years, she was admitted to hospital with mild poliomyelitis. A diagnosis of oligophrenia was mentioned and acromegaly suspected. Behaviour problems, her height and the size of her feet caused a new admission when she was I 1 years old. Her height was then 174 cm, more than 30 cm above average. The finding of a “somewhat large sella” resulted in Xray treatment. Menarche occurred at the age of IS years after treatment with gonadotropin. Menstruation was normal and she had two normal pregnancies when 25 and 31 years old. All endocrinological examinations, including a single determination of serum growth hormone have been normal. Chromosomes were normal. The dermatoglyphic pattern showed a total ridge count (TRC) of 217 and whorls on all fingers. Pneumoencephalography performed at the age of 23 years showed enlarged ventricles, Evans’ index 0.34, and a 5 mm septum pellucidum cyst. She has now an acromegalic appearance and is mentally retarded. She works in a sheltered workshop for the mentally deficient. Her final height is 193 cm.
Son No. 2 / 2 . Sister is healthy and has a normal growth curve. The father is about 1.70 m. Normal delivery 2 weeks after term. Birth weight 4 850 g, length 60 cm. No asphyxia. Normal neonatal period. Motor development was delayed and he was admitted to this department when 81 months old. His height was 85 cm. He had a large dolicocephalic skull, circumference 51.5 cm (4 cm above Acta Paediatr Scand 65
F. Juul Hansen and B . briis
388 Boys
Agelheight IM: 2 r s l Height crn 100,
so’, 1
I
I
I
I
I
I
I
3
5
7
9
11
13
15
I
I
,
17 19 21 Age in months
Fig. 1 . The boy’s growth curve.
90 percentile for 2 years), frontal bossing, hypertelorism, antimongoloid slanting of the eyes, prognathism, and a high-arched palate. The hands and feet were not acromegalic. IQ (Catell) was 85. Pneumoencephalography showed no airfilling of the chiasmatic cistern, but the pituitary fossa was normal. Lateral ventricles were enlarged but in normal position. Cisternal air was n o h a 1 round the brainstem, and the 3rd and 4th ventricles were of normal size. Electroencephalography, brainscan and eye examination were normal. A dissociated development of ossification centres in the hand was found, carpal bone age being approximately 2 years, while the finger region was comparable to 15-18 months. This dissociation persisted at later examinations. Fasting serum growth hormone was 7.4 ng/ml, with a normal suppression during hyperglycemia. Serum somatomedin 0.93 U/ml (normal range: O . G l . 2 U/ml). Serum prolactin 21.5 nglml (normal for adults: 5-30 ng/ml). Chromosomes were normal. Examination of dermatoglyphics showed TRC 178 and whorls on all fingers except the 5th left finger, which had an ulnar sling. Height (see Fig. 1).
cases. The mother had a septum pellucidum cyst, not very uncommon, but this abnormality has been emphazised by others (9, 11, 12). Chromosome examinations with special stains were normal in mother and child, as in all previously studied cases. Several facts point towards prenatal etiology. The children are tall at birth and look alike. Abnormal dermatoglyphics have been observed in a great number of patients, as in our two cases. The embryogenesis of dermatoglyphic patterns is complete by the 18th week (10). Autopsy has never been performed. The etiology and pathophysiology are still unknown, but occurrence of the syndrome in a mother and her son supports the assumption that etiology should be searched for on a genetic level. ACKNOWLEDGEMENTS Serum somatomedin was determined by Dr K. W. Kastrup, Children’s Hospital Fuglebakken, Copenhagen, Denmark, serum prolactin by Dr C. Hanssen, Aker Sykehus, Norway, and dermatoglyphics by Dr E. Niebuhr, University Institute of Genetics, Copenhagen.
REFERENCES 1. Abraham, J. M. & Snodgrass, G. J . A. I.: Sotos’
2.
DISCUSSION The child’s case report is a typical one. The “somewhat large sella” was the only supporting sign of tumour in the mother. All X-rays of the sella turcica have been reviewed and are now described as normal. Most cerebral giants have accelerated skeletal maturation. Dissociated bone age development, as found in our patient, has been reported by others (1, 11). All previous studies of hormones which might influence growth have revealed normal values in serum and/or urine. Somatomedin analyses are available in few patients (7, 8), and prolactin has not been determined before. Our patient had normal values of both hormones. Enlarged ventricles have been found in almost all patients examined, as in our two Acta Prpdiatr Scand 65
3. 4. 5. 6.
7. 8.
9.
syndrome of cerebral gigantism. Arch Dis Child, 44: 203, 1969. Bejar, R. L., Smith, G. F., Park, S., Spellacy, W. N . , Wolfson, S. L. & Nyhan, W. L.: Cerebral gigantism: Concentrations of amino acids in plasma and muscle. JPediatr, 76: 105, 1970. Gardner-Medwin, D.: Cerebral gigantism? Dev Med Child Neurol, 11: 796, 1%9. Gellis, S . S.: Sotos’ syndrome of cerebral gigantism. Yearbook of Pediatrics, 417, 1971. Hooft, C., Schotte, H. &Van Hooren, G.: Gigantisme cerebral familial. Acta Paediatr Belg, 22: 173, 1968. Hook, E. B. & Reynolds, J. W.: Cerebral gigantism: Endocrinological and clinical observations of six patients, including a congenital giant, concordant monozygotic twins, and a child who achieved adult gigantic size. J Pediatr, 70: 900, 1967. Kjellman, B.: Cerebral gigantism. Acta Paediatr Scand, 54: 603, 1965. Lecornu, M.: Le facteur serique de sulfatation (somatomedine) dans les retards de croissance, le gigantisme cerebral et I’acromegalie. Arch Fr Pediatr, 30: 595, 1973. Marie, J., Royer, P., Levtque, B., Debauchez, C. & Rappaport, R.: Gigantisme avec encephalopathie et dysmorphie cranio-faciale. Ann Pediatr, 12: 682, 1965.
-
Pamilial occurrence oj cerebral gigantism 10. Miller, J. R. & Giroux, J.: Dermatoglyphics in pediatric practice. J Pediatr, 69: 302, 1966. I I . Poznanski, A. K. & Stephenson, J. M.: Radiographic
findings in hypothalamic acceleration of growth associated with cerebral atrophy and mental retardation (Cerebral gigantism). Radiology, 88: 446, 1967. I?. Schlack, H. G. & Pheiffer, R. A.: Zerebraler Gigantismus im Kindesalter. Munch Med Wochensrhr, 112: 26, 1970. 13. Schotte, H.: Deux cas de gigantisme cerebral. Acta Paediatr Belg, 2/:412, 1%7.
389
14. Sotos, J. F., Dodge, P. R., Muirhead, D., Crawford, J . D. & Talbot, N . B.: Cerebral gigantism in childhood. N Engl J Med, 271: 109, 1964.
Submitted April I , 1975 Accepted Nov. 20, 1975
( F . J. H.) 0sterbrogade 44 DK-2100 Copenhagen 0 Denmark
Acta Paediatr Scand 65
CASE REPORT
FAMILIAL OCCURRENCE OF CEREBRAL GIGANTISM, SOTOS’ SYNDROME F. J U U L HANSEN and BIRGITTE FRIIS From the Department of Puediatrics, Rigshospitulet, Blegdamsvej, Copenhugen, Denmurk
ABSTRACT. Juul Hansen, F. and Friis, B. (Department of pediatrics, Rigshospitalet, Blegdamsvej, Copenhagen, Denmark). Familial Occurrence of cerebral gigantism, Sotos’ syndrome. Acta Paediatr Scand, 65: 387, 1976.Eince the original description of cerebral gigantism, about 85 cnses have been reported. Four papers comment on familial occurrence but never in parents and their children. This paper describes the syndrome in a mother and her child, which, together with facts pointing towards prenatal etiology, such as excessive birthweight, striking mutual resemblance and abnormal dermatoglyphics, points to a genetic defect. Previous endocrine studies are enlarged by the findings of normal serum somatomedin and serum prolactin.
KEY WORDS: Cerebral gigantism, familial Occurrence, somatomedin, prolactin
In 1964 Sotos and associates (14) described the syndrome of cerebral gigantism, consisting of a nonprogressive neurological disorder, mental deficiency, cranio-facial dysmorphology, accelerated infantile growth with acromegalic characteristics and advanced skeletal maturation without endocrinological abnormalities. Some 85 cases have been reported. It has been assumed that the condition is caused by a diencephalic lesion, but the etiology and pathophysiology have not been elucidated. The symptom complex is, however, generally recognized as a distinct entity (3, 4), which can easily be separated from other diencephalic syndromes. Familial occurrence has been described in four papers (2, 5 , 6, 13) but never in parents and their children. We therefore wish to report a case of cerebral gigantism in a mother and her son, as a contribution to the discussion of etiology of the syndrome. CASEREPORTS Mother No. 9/11. Eight of her brothers and sisters have children, all of normal height. No neurologic or endocrine disease 25-762813
was present in the family. Birthweight 6000 g. She was always taller than children of the same age. She started school at the age of 7 years and eventually managed normal school. At the age of 9 years, she was admitted to hospital with mild poliomyelitis. A diagnosis of oligophrenia was mentioned and acromegaly suspected. Behaviour problems, her height and the size of her feet caused a new admission when she was I 1 years old. Her height was then 174 cm, more than 30 cm above average. The finding of a “somewhat large sella” resulted in Xray treatment. Menarche occurred at the age of IS years after treatment with gonadotropin. Menstruation was normal and she had two normal pregnancies when 25 and 31 years old. All endocrinological examinations, including a single determination of serum growth hormone have been normal. Chromosomes were normal. The dermatoglyphic pattern showed a total ridge count (TRC) of 217 and whorls on all fingers. Pneumoencephalography performed at the age of 23 years showed enlarged ventricles, Evans’ index 0.34, and a 5 mm septum pellucidum cyst. She has now an acromegalic appearance and is mentally retarded. She works in a sheltered workshop for the mentally deficient. Her final height is 193 cm.
Son No. 2 / 2 . Sister is healthy and has a normal growth curve. The father is about 1.70 m. Normal delivery 2 weeks after term. Birth weight 4 850 g, length 60 cm. No asphyxia. Normal neonatal period. Motor development was delayed and he was admitted to this department when 81 months old. His height was 85 cm. He had a large dolicocephalic skull, circumference 51.5 cm (4 cm above Acta Paediatr Scand 65
F. Juul Hansen and B . briis
388 Boys
Agelheight IM: 2 r s l Height crn 100,
so’, 1
I
I
I
I
I
I
I
3
5
7
9
11
13
15
I
I
,
17 19 21 Age in months
Fig. 1 . The boy’s growth curve.
90 percentile for 2 years), frontal bossing, hypertelorism, antimongoloid slanting of the eyes, prognathism, and a high-arched palate. The hands and feet were not acromegalic. IQ (Catell) was 85. Pneumoencephalography showed no airfilling of the chiasmatic cistern, but the pituitary fossa was normal. Lateral ventricles were enlarged but in normal position. Cisternal air was n o h a 1 round the brainstem, and the 3rd and 4th ventricles were of normal size. Electroencephalography, brainscan and eye examination were normal. A dissociated development of ossification centres in the hand was found, carpal bone age being approximately 2 years, while the finger region was comparable to 15-18 months. This dissociation persisted at later examinations. Fasting serum growth hormone was 7.4 ng/ml, with a normal suppression during hyperglycemia. Serum somatomedin 0.93 U/ml (normal range: O . G l . 2 U/ml). Serum prolactin 21.5 nglml (normal for adults: 5-30 ng/ml). Chromosomes were normal. Examination of dermatoglyphics showed TRC 178 and whorls on all fingers except the 5th left finger, which had an ulnar sling. Height (see Fig. 1).
cases. The mother had a septum pellucidum cyst, not very uncommon, but this abnormality has been emphazised by others (9, 11, 12). Chromosome examinations with special stains were normal in mother and child, as in all previously studied cases. Several facts point towards prenatal etiology. The children are tall at birth and look alike. Abnormal dermatoglyphics have been observed in a great number of patients, as in our two cases. The embryogenesis of dermatoglyphic patterns is complete by the 18th week (10). Autopsy has never been performed. The etiology and pathophysiology are still unknown, but occurrence of the syndrome in a mother and her son supports the assumption that etiology should be searched for on a genetic level. ACKNOWLEDGEMENTS Serum somatomedin was determined by Dr K. W. Kastrup, Children’s Hospital Fuglebakken, Copenhagen, Denmark, serum prolactin by Dr C. Hanssen, Aker Sykehus, Norway, and dermatoglyphics by Dr E. Niebuhr, University Institute of Genetics, Copenhagen.
REFERENCES 1. Abraham, J. M. & Snodgrass, G. J . A. I.: Sotos’
2.
DISCUSSION The child’s case report is a typical one. The “somewhat large sella” was the only supporting sign of tumour in the mother. All X-rays of the sella turcica have been reviewed and are now described as normal. Most cerebral giants have accelerated skeletal maturation. Dissociated bone age development, as found in our patient, has been reported by others (1, 11). All previous studies of hormones which might influence growth have revealed normal values in serum and/or urine. Somatomedin analyses are available in few patients (7, 8), and prolactin has not been determined before. Our patient had normal values of both hormones. Enlarged ventricles have been found in almost all patients examined, as in our two Acta Prpdiatr Scand 65
3. 4. 5. 6.
7. 8.
9.
syndrome of cerebral gigantism. Arch Dis Child, 44: 203, 1969. Bejar, R. L., Smith, G. F., Park, S., Spellacy, W. N . , Wolfson, S. L. & Nyhan, W. L.: Cerebral gigantism: Concentrations of amino acids in plasma and muscle. JPediatr, 76: 105, 1970. Gardner-Medwin, D.: Cerebral gigantism? Dev Med Child Neurol, 11: 796, 1%9. Gellis, S . S.: Sotos’ syndrome of cerebral gigantism. Yearbook of Pediatrics, 417, 1971. Hooft, C., Schotte, H. &Van Hooren, G.: Gigantisme cerebral familial. Acta Paediatr Belg, 22: 173, 1968. Hook, E. B. & Reynolds, J. W.: Cerebral gigantism: Endocrinological and clinical observations of six patients, including a congenital giant, concordant monozygotic twins, and a child who achieved adult gigantic size. J Pediatr, 70: 900, 1967. Kjellman, B.: Cerebral gigantism. Acta Paediatr Scand, 54: 603, 1965. Lecornu, M.: Le facteur serique de sulfatation (somatomedine) dans les retards de croissance, le gigantisme cerebral et I’acromegalie. Arch Fr Pediatr, 30: 595, 1973. Marie, J., Royer, P., Levtque, B., Debauchez, C. & Rappaport, R.: Gigantisme avec encephalopathie et dysmorphie cranio-faciale. Ann Pediatr, 12: 682, 1965.
-
Pamilial occurrence oj cerebral gigantism 10. Miller, J. R. & Giroux, J.: Dermatoglyphics in pediatric practice. J Pediatr, 69: 302, 1966. I I . Poznanski, A. K. & Stephenson, J. M.: Radiographic
findings in hypothalamic acceleration of growth associated with cerebral atrophy and mental retardation (Cerebral gigantism). Radiology, 88: 446, 1967. I?. Schlack, H. G. & Pheiffer, R. A.: Zerebraler Gigantismus im Kindesalter. Munch Med Wochensrhr, 112: 26, 1970. 13. Schotte, H.: Deux cas de gigantisme cerebral. Acta Paediatr Belg, 2/:412, 1%7.
389
14. Sotos, J. F., Dodge, P. R., Muirhead, D., Crawford, J . D. & Talbot, N . B.: Cerebral gigantism in childhood. N Engl J Med, 271: 109, 1964.
Submitted April I , 1975 Accepted Nov. 20, 1975
( F . J. H.) 0sterbrogade 44 DK-2100 Copenhagen 0 Denmark
Acta Paediatr Scand 65
