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Japanese monozygotic twins with Rett syndrome
Brain & Development 19 (1997) 568–570
Case report
Japanese monozygotic twins with Rett syndrome Atsushi Ogawa a ,*, Akihisa Mitsudome a, Sawa Yasumoto a, Toshimichi Matsumoto b a
Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka 814-80, Japan b Matsumoto Pediatric Clinic, 4-8-16, Nishijin, Sawara-ku, Fukuoka 814-01, Japan
Received 21 May 1996; revised version received 6 October 1997; accepted 7 October 1997
Abstract We present a study of 28-year-old Japanese monozygotic female twins with Rett syndrome (RS). To our knowledge, this is the first report of monozygotic twins with RS from Japanese family. There are some differences between twins about seizures, scoliosis and stereotypical hand movements during adolescence. Monozygosity was confirmed by both blood typing and HLA titers. 1997 Elsevier Science B.V. Keywords: Rett syndrome; Monozygotic twins; Female X-linked disease
1. Introduction Rett syndrome (RS), which was first described relatively recently [1], affects only females, and is characterized by a progressive deterioration of neurological status and impairment of psychomotor development. Compelling evidence for a genetic basis was developed through an analysis of monozygotic and dizygotic twins, one or both of whom had RS [2]. To date, seven pairs of monozygotic twins with RS have been reported. Eleven pairs of dizygotic twins are known to exist, four of which are female only, and seven of which comprise a female and a male twin. All 11 pairs are discordant and only one twin is affected, always the female [3]. Coleman et al. [4] and Bruck et al. [5] have described differences between presumed monozygotic twins. We report 28-year-old Japanese monozygotic female twins with RS.
2. Case report These Japanese twins were born in 1967 at 40 weeks gestation to non-consanguineous parents. Their mother was 27 years old and their father was 35 years old at the time of their birth. Twin A weighed 2400 g; twin B 2500 g. * Corresponding author. Tel.: +81 92 801 1011; fax: +81 92 863 1970.
0387-7604/97/$17.00 1997 Elsevier Science B.V. All rights reserved PII S0387-7604 (97 )0 0084-3
Labor, delivery and the neonatal period were unremarkable. In the first year, the twins appeared normal, but delayed development gradually became evident. Twin A walked at 15 months and Twin B at 18 months. Further deterioration then led to severe mental retardation. Each child was able to speak only a few simple words by the age of 1, but stopped speaking at the age of 4. Twin B developed generalized tonic seizures at age 6. Both twins started characteristic stereotypic hand-washing movements in front of the chest and hand biting at age 4. The twins were admitted to our hospital when they were 10 years old. Both showed severe mental retardation, autistic behavior, loss of purposeful use of the hands, jerky truncal ataxia, and microcephaly (Fig. 1a,b). EEG results indicated spike activity in both cases. Inborn errors of metabolism were ruled out. Ocular fundi appeared normal. At this time, RS had not yet been defined by the medical community. Our diagnosis was mental retardation in twin A and epilepsy with mental retardation in twin B. In 1993, they returned to our hospital. Twin A was then 145.0 cm tall, weighed 27 kg and her head circumference was 50.4 cm. Twin B was 141.3 cm tall, weighed 22 kg and her head circumference was 50.0 cm. They demonstrated autistic behavior, incessant giggling, and an inability to walk unaided (Fig. 1c,d). Twin B had evidence of scoliosis, whereas twin A did not. Twin A’s stereotypic hand movements stopped at age 20, but twin B continued to rub her
A. Ogawa et al. / Brain & Developlment 19 (1997) 568–570
569
Fig. 1. (a,b) The RS twins at 10 years of age (left, twin A; right, twin B). Twin B shows typical hand stereotypics. (c,d) Twins at 24 years of age (left, twin A; right, twin B).
hands. EEG results were abnormal with high voltage paroxysms in both girls.
3. Genetic study Analysis of blood types and HLA typing confirmed monozygosity (Table 1).
4. Discussion RS, which affects only females, has been reported in almost 40 countries and on virtually every continent. No race or ethnic group appears to be immune to this disorder [6]. Evidence is required to establish the cause. Twin case reports [4,5,7,8] and their family histories [9–12], together with chromosomal investigation, indicates an X-linked inheritance. Engerstrom and Forslund [13] reported a case of mother and daughter with RS. The most logical genetic
explanation, based on existing evidence, is that RS is an Xlinked dominant disorder that is lethal in males [11]. Coleman et al. [4] described slightly differing rates of development with some clinical dissimilarities in monozygotic twins with RS. They concluded that studies in monozygotic twins would facilitate understanding of the variability in clinical expression of this disease. Bruck et al. [5] reported early developmental differences between twins with RS. In their study, one twin was recognized as being abnormal at birth, while no abnormality was suspected in the other twin until she was about 12 months old. The twins in our study are now in stage III of the disease, according to Hagberg’s criteria [14]. The two had discordant characteristics with regard to seizures, scoliosis and stereotypic hand movements during adolescence. The fact that they are monozygotic twins, exposed to the same environment, suggests a wider manifestation than previously suspected. Existing evidence is insufficient to determine whether RS is an inherited disorder, and no specific chromosomal region
570
A. Ogawa et al. / Brain & Development 19 (1997) 568–570
References
Table 1 Blood types and HLA typing of the twins
Blood type ABC Rh MN P Kidd Lewis AcP EsD PGM1 Hp Pi Tf Gc AHSG ORM1 ORM2 CIR HF ITI Gm HLA typing Locus A Locus B Locus Bw Locus C Locus DR Locus DRw
Twin A
Twin B
B CCDee MN Pl a+b− Le (a − b + ) B 2- - 1 1A - 1A 2- - 2 M1M2 C1 1F - 1S 2- - 1 Fl M 2- - 1 AB 1 1+2+3+
B CCDee MN Pl a+b− Le (a − b + ) B 2- - 1 1A - 1A 2- - 2 M1M2 C1 1F - 1S 2- - 1 Fl M 2- - 1 AB 1 1+2+3+
24 52 46 4 1 8 15 52
24 52 46 4 1 8 15 52
has been identified. Further investigation, using a genetic approach through family studies, is needed to clarify the cause and the genetic aspects of RS.
[1] Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett’s syndrome: report of 35 cases. Ann Neurol 1983;14:471–479. [2] Percy AK. The Rett syndrome: the recent advances in genetic studies in the USA. Brain Dev 1992;14(suppl):S101–S103. [3] Anvret M, Wahlstrom J, Akesson H-O. In: Hagberg B, editor. London: MacKeith Press, 1993:99–107. [4] Coleman M, Naidu S, Murphy M, Pines M, Bias W. A set of monozygotic twins with Rett syndrome. Brain Dev 1987;9:475–478. [5] Bruck I, Philippart M, Giraldi D, Antoniuk S. Difference in early development of presumed monozygotic twins with Rett syndrome. Am J Med Genet 1991;39:415–417. [6] Iyama CM. In: Advances in pediatrics. Mosby Year Book, 1993:217–245. [7] Tariverdian G, Kantner G, Vogel F. A monozygotic twin pair with Rett syndrome. Hum Genet 1987;75:88–90. [8] Partington MW. Rett syndrome in monozygotic twins. Am J Med Genet 1988;29:633–637. [9] Anvret M, Johansson IM, Wahlstrom J, Hagberg B. Linkage analysis of the Rett syndrome using human chromosomal specific probes. Brain Dev 1985;7:361–364. [10] Hanefeld F, Hanefeld U, Wilichowski E, Schmidtke J. Rett syndrome – search for genetic markers. Am J Med Genet 1986;24:377–382. [11] Comings DE. The genetics of Rett syndrome: the consequences of a disorder where every case is a new mutation. Am J Med Genet 1986;24:383–388. [12] Al-Mateen M, Philippart M, Shields WD. Rett syndrome. A commonly overlooked progressive encephalopathy in girls. Am J Dis Child 1986;140:761–765. [13] Engerstrom IW, Forslund M. Mother and daughter with Rett syndrome [letter]. Dev Med Child Neurol 1992;34:1022–1023. [14] Hagberg B, Witt EI. Rett syndrome: a suggested staging system for describing impairment profile with increasing age towards adolescence. Am J Med Genet Suppl 1986;24:47–59.
Case report
Japanese monozygotic twins with Rett syndrome Atsushi Ogawa a ,*, Akihisa Mitsudome a, Sawa Yasumoto a, Toshimichi Matsumoto b a
Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka 814-80, Japan b Matsumoto Pediatric Clinic, 4-8-16, Nishijin, Sawara-ku, Fukuoka 814-01, Japan
Received 21 May 1996; revised version received 6 October 1997; accepted 7 October 1997
Abstract We present a study of 28-year-old Japanese monozygotic female twins with Rett syndrome (RS). To our knowledge, this is the first report of monozygotic twins with RS from Japanese family. There are some differences between twins about seizures, scoliosis and stereotypical hand movements during adolescence. Monozygosity was confirmed by both blood typing and HLA titers. 1997 Elsevier Science B.V. Keywords: Rett syndrome; Monozygotic twins; Female X-linked disease
1. Introduction Rett syndrome (RS), which was first described relatively recently [1], affects only females, and is characterized by a progressive deterioration of neurological status and impairment of psychomotor development. Compelling evidence for a genetic basis was developed through an analysis of monozygotic and dizygotic twins, one or both of whom had RS [2]. To date, seven pairs of monozygotic twins with RS have been reported. Eleven pairs of dizygotic twins are known to exist, four of which are female only, and seven of which comprise a female and a male twin. All 11 pairs are discordant and only one twin is affected, always the female [3]. Coleman et al. [4] and Bruck et al. [5] have described differences between presumed monozygotic twins. We report 28-year-old Japanese monozygotic female twins with RS.
2. Case report These Japanese twins were born in 1967 at 40 weeks gestation to non-consanguineous parents. Their mother was 27 years old and their father was 35 years old at the time of their birth. Twin A weighed 2400 g; twin B 2500 g. * Corresponding author. Tel.: +81 92 801 1011; fax: +81 92 863 1970.
0387-7604/97/$17.00 1997 Elsevier Science B.V. All rights reserved PII S0387-7604 (97 )0 0084-3
Labor, delivery and the neonatal period were unremarkable. In the first year, the twins appeared normal, but delayed development gradually became evident. Twin A walked at 15 months and Twin B at 18 months. Further deterioration then led to severe mental retardation. Each child was able to speak only a few simple words by the age of 1, but stopped speaking at the age of 4. Twin B developed generalized tonic seizures at age 6. Both twins started characteristic stereotypic hand-washing movements in front of the chest and hand biting at age 4. The twins were admitted to our hospital when they were 10 years old. Both showed severe mental retardation, autistic behavior, loss of purposeful use of the hands, jerky truncal ataxia, and microcephaly (Fig. 1a,b). EEG results indicated spike activity in both cases. Inborn errors of metabolism were ruled out. Ocular fundi appeared normal. At this time, RS had not yet been defined by the medical community. Our diagnosis was mental retardation in twin A and epilepsy with mental retardation in twin B. In 1993, they returned to our hospital. Twin A was then 145.0 cm tall, weighed 27 kg and her head circumference was 50.4 cm. Twin B was 141.3 cm tall, weighed 22 kg and her head circumference was 50.0 cm. They demonstrated autistic behavior, incessant giggling, and an inability to walk unaided (Fig. 1c,d). Twin B had evidence of scoliosis, whereas twin A did not. Twin A’s stereotypic hand movements stopped at age 20, but twin B continued to rub her
A. Ogawa et al. / Brain & Developlment 19 (1997) 568–570
569
Fig. 1. (a,b) The RS twins at 10 years of age (left, twin A; right, twin B). Twin B shows typical hand stereotypics. (c,d) Twins at 24 years of age (left, twin A; right, twin B).
hands. EEG results were abnormal with high voltage paroxysms in both girls.
3. Genetic study Analysis of blood types and HLA typing confirmed monozygosity (Table 1).
4. Discussion RS, which affects only females, has been reported in almost 40 countries and on virtually every continent. No race or ethnic group appears to be immune to this disorder [6]. Evidence is required to establish the cause. Twin case reports [4,5,7,8] and their family histories [9–12], together with chromosomal investigation, indicates an X-linked inheritance. Engerstrom and Forslund [13] reported a case of mother and daughter with RS. The most logical genetic
explanation, based on existing evidence, is that RS is an Xlinked dominant disorder that is lethal in males [11]. Coleman et al. [4] described slightly differing rates of development with some clinical dissimilarities in monozygotic twins with RS. They concluded that studies in monozygotic twins would facilitate understanding of the variability in clinical expression of this disease. Bruck et al. [5] reported early developmental differences between twins with RS. In their study, one twin was recognized as being abnormal at birth, while no abnormality was suspected in the other twin until she was about 12 months old. The twins in our study are now in stage III of the disease, according to Hagberg’s criteria [14]. The two had discordant characteristics with regard to seizures, scoliosis and stereotypic hand movements during adolescence. The fact that they are monozygotic twins, exposed to the same environment, suggests a wider manifestation than previously suspected. Existing evidence is insufficient to determine whether RS is an inherited disorder, and no specific chromosomal region
570
A. Ogawa et al. / Brain & Development 19 (1997) 568–570
References
Table 1 Blood types and HLA typing of the twins
Blood type ABC Rh MN P Kidd Lewis AcP EsD PGM1 Hp Pi Tf Gc AHSG ORM1 ORM2 CIR HF ITI Gm HLA typing Locus A Locus B Locus Bw Locus C Locus DR Locus DRw
Twin A
Twin B
B CCDee MN Pl a+b− Le (a − b + ) B 2- - 1 1A - 1A 2- - 2 M1M2 C1 1F - 1S 2- - 1 Fl M 2- - 1 AB 1 1+2+3+
B CCDee MN Pl a+b− Le (a − b + ) B 2- - 1 1A - 1A 2- - 2 M1M2 C1 1F - 1S 2- - 1 Fl M 2- - 1 AB 1 1+2+3+
24 52 46 4 1 8 15 52
24 52 46 4 1 8 15 52
has been identified. Further investigation, using a genetic approach through family studies, is needed to clarify the cause and the genetic aspects of RS.
[1] Hagberg B, Aicardi J, Dias K, Ramos O. A progressive syndrome of autism, dementia, ataxia, and loss of purposeful hand use in girls: Rett’s syndrome: report of 35 cases. Ann Neurol 1983;14:471–479. [2] Percy AK. The Rett syndrome: the recent advances in genetic studies in the USA. Brain Dev 1992;14(suppl):S101–S103. [3] Anvret M, Wahlstrom J, Akesson H-O. In: Hagberg B, editor. London: MacKeith Press, 1993:99–107. [4] Coleman M, Naidu S, Murphy M, Pines M, Bias W. A set of monozygotic twins with Rett syndrome. Brain Dev 1987;9:475–478. [5] Bruck I, Philippart M, Giraldi D, Antoniuk S. Difference in early development of presumed monozygotic twins with Rett syndrome. Am J Med Genet 1991;39:415–417. [6] Iyama CM. In: Advances in pediatrics. Mosby Year Book, 1993:217–245. [7] Tariverdian G, Kantner G, Vogel F. A monozygotic twin pair with Rett syndrome. Hum Genet 1987;75:88–90. [8] Partington MW. Rett syndrome in monozygotic twins. Am J Med Genet 1988;29:633–637. [9] Anvret M, Johansson IM, Wahlstrom J, Hagberg B. Linkage analysis of the Rett syndrome using human chromosomal specific probes. Brain Dev 1985;7:361–364. [10] Hanefeld F, Hanefeld U, Wilichowski E, Schmidtke J. Rett syndrome – search for genetic markers. Am J Med Genet 1986;24:377–382. [11] Comings DE. The genetics of Rett syndrome: the consequences of a disorder where every case is a new mutation. Am J Med Genet 1986;24:383–388. [12] Al-Mateen M, Philippart M, Shields WD. Rett syndrome. A commonly overlooked progressive encephalopathy in girls. Am J Dis Child 1986;140:761–765. [13] Engerstrom IW, Forslund M. Mother and daughter with Rett syndrome [letter]. Dev Med Child Neurol 1992;34:1022–1023. [14] Hagberg B, Witt EI. Rett syndrome: a suggested staging system for describing impairment profile with increasing age towards adolescence. Am J Med Genet Suppl 1986;24:47–59.