XXXXX Syndrome

XXXXX Syndrome 49,XXXXX (pentasomy X) is a rare sex chromosome aneu- 2. Craniofacial features ploidy. The birth prevalence of pentasomy X is estimated to be a. Microcephaly 1 in 85,000 females. b. Flattened occiput c. Epicanthus d. Upslanting palpebral fissures GENETICS/BASIC DEFECTS e. Ocular hypertelorism 1. Etiology: Three extra X chromosomes are responsible for f. Uncoordinated eye movements the pentasomy X syndrome. g. Flat broad nose 2. Occurrence of a 49,XXXXX complement: secondary to h. Cleft palate sequential non-disjunctions in meiosis I and meiosis II in i. Low-set ears the mother j. Malformed teeth a. Involves the survival of both X chromosomes in a sin- 3. Skeletal abnormalities gle oocytes through both meiotic divisions a. Short neck i. Once between homologous X chromosomes at b. Lax joints the first meiosis c. Multiple dislocations ii. Twice between sister chromatids in both X chro- i. Shoulders mosomes in the secondary oocytes at the second ii. Elbows meiosis iii. Hips b. Followed by the fertilization by a sperm contributing d. Radioulnar synostosis the 5th chromosome X e. Spinal abnormalities 3. Formation of four Barr bodies f. Clinodactyly of the 5th fingers a. Lyon hypothesis g. Lower leg abnormalities i. Inactivation of all X chromosomes but one i. Genu valgus ii. Account for the viability of the X-chromosome ii. Talipes aneuploidies iii. Metatarsus varus b. Inactivation of four X chromosomes resulting in four h. Delayed bone age Barr bodies 4. Congenital heart defects 4. Effect of supernumerary X chromosomes: a direct rela- a. Ventricular septal defect tionship between the number of supernumerary X chro- b. Patent ductus arteriosus mosomes and phenotypic abnormalities and mental 5. Abnormal lobulation of the lungs retardation, with each additional chromosome increasing 6. Renal hypoplasia the severity 7. Sexual development a. Affects somatic development most significantly a. Delayed puberty i. Skeletal abnormalities b. Incomplete secondary sexual development ii. Cardiovascular abnormalities c. Small uterus b. Delays sexual development d. Hypoplastic/absent ovaries c. Affects cognitive development i. Composed mainly of stroma and atrophic follicles i. Severe mental retardation ii. Absence of ova ii. Language delay (both expressive and receptive iii. Unilateral absence of an ovary reported language) e. Reduced fertility iii. Behavioral problems 8. Normal external genitalia 9. Dermatoglyphics a. Finger-dermal-ridge hypoplasia and a low total ridge CLINICAL FEATURES count, consistent with the inverse proportion between 1. Growth and development the number of X chromosomes and the total ridge a. Prenatal growth retardation count (exceptions exist) b. Small birth weight b. Transverse palmar creases c. Low postnatal weight d. Failure to thrive DIAGNOSTIC INVESTIGATIONS e. Hypotonia 1. Chromosome analysis f. Short stature a. 49,XXXXX karyotype g. Delayed psychomotor retardation b. Fluorescence in situ hybridization (FISH), using h. Mental retardation DNA probe for α-satellite sequence in chromosome 1064 XXXXX SYNDROME 1065 X (DXZ1), reveals five signals representing the pres- Dryer RF, Patil SR, Zellweger HU, et al.: Pentasomy X with multiple disloca- ence of XXXXX tions. Am J Med Genet 4:313–321, 1979. Fryns JP, Kleczkowska A, Petit P, et al.: X-chromosome polysomy in the 2. Radiography female: personal experience and review of the literature. Clin Genet a. Dislocations of the elbows and/or hips 23:341–349, 1983. b. Radioulnar synostosis Funderburk SJ, Valente M, Klisak I: Pentasomy X: report of patient and studies c. Clinodactyly of X-inactivation. Am J Med Genet 8:27–33, 1981. Kassai R, Hamada I, Furuta H, et al.: Penta X syndrome: A case report with GENETIC COUNSELING review of the literature. Am J Med Genet 40:51–56, 1991. Kesaree N, Woolley PV Jr: A phenotypic female with 49 chromosomes, pre- 1. Recurrence risk sumably XXXXX. J Pediatr 63:1099–1103, 1963. a. Patient’s sib: not increased Leal CA, Belmont JW, Nachtman R, et al.: parental origin of the extra chromo- b. Patient’s offspring: not reported due to severe mental somes in polysomy X. Hum Genet 94:423–426, 1994. Linden MG, Bender BG, Robinson A: Sex chromosome tetrasomy and penta- retardation somy. Pediatrics 96:672–682, 1995. 2. Prenatal diagnosis Martini G, Carillo G, Catizone F, et al.: On the parental origin of the X’s in a a. Ultrasonography: bilateral radioulnar synostosis prenatally diagnosed 49,XXXXX syndrome. Prenat Diagn 13:763–766, b. Amniocentesis and CVS 1993. i. Chromosome analysis Monheit A, Francke U, Saunders B, et al.: The penta-X syndrome. J Med Genet 17:392–396, 1980. ii. FISH using DNA probe (DXZ1) applied to Myles TD, Burd L, Font G, et al.: Dandy-Walker malformation in a fetus uncultured amniocytes with pentasomy X (49,XXXXX) prenatally diagnosed by fluores- 3. Management cence in situ hybridization technique. Fetal Diagn Ther 10:333–336, a. Physical/occupational therapy 1995. b. Speech therapy Sepulveda W, Ivankovic M, Be C, et al.: Sex chromosome pentasomy (49,XXXXY) presenting as cystic hygroma at 16 weeks’ gestation. Prenat Diagn 19:257–259, 1999. REFERENCES Sergovich F, Uilenberg C, Pozsony J: The 49,XXXXX chromosome constitu- Archidiacono N, Rocchi M, Valente M, et al.: X pentasomy: A case and review. tion: similarities to the 49,XXXXY condition. J Pediatr 78:285–290, Hum Genet 52:69–77, 1979. 1971. Brody J, Fitzgerald MG, Spiers ASD: A female child with five X chromo- Silengo MC, Davi GF, Franceschini P: The 49XXXXX syndrome. Report of a somes. J Pediatr 70:105–109, 1967. case with 48XXXX/49XXXXX mosaicism. Acta Paediatr Scand Deng H-X, Abe K, Kondo I, et al.: Parental origin and mechanism of formation 68:769–771, 1979. of polysomy X: an XXXXX case and four XXXXY cases determined Toussi T, Hala F, Lesage R, et al.: Renal hypodysplasia and unilateral ovarian with RFLPs. Hum Genet 86:541–544, 1991. agenesis in the penta-X syndrome. Am J Med Genet 6:153–162, 1980. 1066 XXXXX SYNDROME Fig. 1. The first reported case of 49,XXXXX at infancy (A) and adult- hood (B) with 4 Barr bodies (C), two drumsticks in a polymorphonu- clear leukocyte (D), and a karyotype of 49,XXXXX (E). XXXXX SYNDROME 1067 Fig. 2. A girl with 49,XXXXX syndrome at birth (A), 6 month (B), and 2 years 4 months (C)..

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