XXX Syndrome
Females with a 47,XXX karyotype were first described by Jacobs et al. in 1959. The incidence of 47,XXX among female newborns is approximately 1 in 1000 live births.
GENETICS/BASIC DEFECTS
1. Etiology: an extra chromosome X is responsible for 47,XXX
2. Mechanism of the origin for the 47,XXX condition a. Almost all 47,XXX result from maternal nondis-
junction
b. Typically at meiosis I
CLINICAL FEATURES
1. No specific phenotype exists in 47,XXX females 2. A higher incidence of minor anomalies
a. Epicanthal folds
b. Upslanting palpebral fissures c. Ear abnormalities
d. Clinodactyly 3. Growth and development
a. Birth weights tend to be slightly lower than the gen- eral population.
b. Taller in older children c. Relative microcephaly
d. At risk for mild speech/language and motor delays and learning disabilities
e. Intelligence i. Normal range
ii. Lower intelligence quotients (10–15 points) in comparison to unaffected sibs
4. Gonadal structures and function a. Heterosexual
b. Normal secondary sexual characteristics c. Normal menstruation
d. Fertility usually normal e. Late menarche
f. Occasional amenorrhea g. Premature ovarian failure h. Sterility with streak gonads
5. Congenital anomalies reported in a very small number of patients
a. Urogenital tract abnormalities b. Brain abnormalities
c. Skeletal abnormalities d. Congenital heart defects e. Craniofacial abnormalities 6. Adaptation status: variable
a. At risk for intellectual and psychological problems b. 47,XXX women during adolescence and young
adulthood
i. Less well adapted ii. With more stress
iii. With work, leisure, and relationship problems iv. With a lower IQ
v. With more psychopathology when contrasted with the comparison group
c. Most 47,XXX women i. Self sufficient
ii. Functioning reasonably well
DIAGNOSTIC INVESTIGATIONS
1. Chromosome analysis
2. Psychological and psychiatric evaluation when needed
GENETIC COUNSELING
1. Recurrence risk
a. Patient’s sib: not increased b. Patient’s offspring
i. An increased risk of a cytogenetically abnormal child but the extent of the risk cannot yet be determined
ii. Majority of offspring normal
2. Prenatal diagnosis by fetal karyotyping from amniocytes or CVS
3. Management
a. Infancy/toddler: assess milestones b. Childhood
i. Assess school performance ii. Provide intervention if needed
a) Speech/language therapy b) Physical/occupational therapy c) Educational remediation
c. Adolescence: usually no intervention needed d. Adult adulthood: annual physical examination
REFERENCES
Barr ML, Sergovich FR, Carr DH, et al.: The triplo X female. Can Med Assoc J 101:247–258, 1969.
Bender BG, Harmon RJ, Linden MG, et al.: Psychosocial competence of uns- elected young adults with sex chromosome abnormalities. Am J Med Genet 88:200–206, 1999.
Chudley AE, Stoeber GP, Greenberg CR: Intrauterine growth retardation and minor anomalies in 47,XXX children. Birth Defects Orig Artic Ser 26:267–272, 1990.
Dewhurst J: Fertility in 47,XXX and 45,X patients. J Med Genet 15:132–135, 1978.
Evans JA, de von Flindt R, Greenberg C, et al.: A cytogenetic survey of 14,069 newborn infants. IV. Further follow up on the children with sex chromo- some anomalies. Birth Defects Orig Artic Ser 18(4):169–184, 1982.
Harmon RJ, Bender BG, Linden MG, et al.: Transition from adolescence to early adulthood: adaptation and psychiatric status of women with 47,XXX. J Am Acad Child Adolesc Psychiatry 37:286–291, 1998.
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1062 XXX SYNDROME
Hassold T, Arnovitz K, Jacobs PA, et al.: The parental origin of the missing or additional chromosome in 45,X and 47,XXX females. Birth Defects Orig Artic Ser 26:297–304, 1990.
Jacobs PA: The incidence and etiology of sex chromosome abnormalities in man. Birth Defects Orig Artic Ser XV(1):3–14, 1979.
Linden MG, Bender BG, Harmon RJ, et al.: 47,XXX: what is the prognosis?
Pediatrics 82:619–630, 1988.
Linden MG, Bender BG, Robinson A: Genetic counseling for sex chromosome abnormalities. Am J Med Genet 110:3–10, 2002.
May KM, Jacobs PA, Lee M, et al.: The parental origin of the extra X chromo- some in 47,XXX females. Am J Hum Genet 46:754–761, 1990.
Ogata T, Matsuo M, Muroya K, et al.: 47,XXX male: A clinical and molecular study. Am J Med Genet 98:353–356, 2001.
Pennington B, Puck M, Robinson A: Language and cognitive development in 47,XXX females followed since birth. Behav Genet 10:31–41, 1980.
Robinson A, Lubs HA, Nielsen J, et al.: Summary of clinical findings: profiles of children with 47,XXY, 47,XXX and 47,XYY karyotypes. Birth Defects Orig Artic Ser 15:261–266, 1979.
Fig. 2. A girl with 47,XXX showing normal phenotype.
Fig. 3. 47,XXX karyotype.
XXX SYNDROME 1063
Fig. 1. A girl with 47,XXX at different ages showing normal pheno- type.
