XANTHOGRANULOMATOSIS (ERDHEIM–CHESTER DISEASE)
DESCRIPTION Erdheim–Chester disease is a rare non-Langerhans form of histiocytosis with a poor prognosis. This disease occurs most commonly in patients older than 50 presenting with xanthoma-like skin nodules and bilateral lower limb bone pain. More disseminated forms of the disease can have renal failure caused by retroperitoneal and perinephric infiltrative or constrictive changes. These patients can also have cardiopulmonary insufficiency and CNS involvement and may have a progressive and fatal disease. The pathophysiology is unknown with limited treatments.
REFERENCE
Jordan MD, Filipovich AH. Histiocytic Disorders. In: Hoffman R, Benz EJ, Silberstein LE, Heslop HE, Weitz JI, Anastasi J, eds. Hoffman: Hematology: Basic Principles and Practice. 6th ed. Philadelphia, PA: Saunders; 2013.
XANTHOMA, BLADDER
DESCRIPTION Collection of foamy histocytes found in the lamina propria in patients with disorders of lipid metabolism.
REFERENCE
Nishimura K, Nozawa M, Hara T, et al. Xanthoma of the bladder. J Urol. 1995;153:1912–1913.
X-LINKED SPINAL AND BULBAR ATROPHY SYNDROME (KENNEDY SYNDROME)
DESCRIPTION Kennedy syndrome is a late-onset, bulbar–spinal type of muscular atrophy. There is an X-linked recessive inheritance genetic marker CAG repeat sequences in the androgen receptor gene (on chromosome X). The majority of evidence of altered androgen sensitivity is restricted to exaggerated or persistent adolescent gynecomastia, and the mildly high LH, testosterone, and estradiol levels characteristic of other forms of androgen insensitivity. The condition becomes prominent in the 4th–5th decades, with proximal muscle wasting and weakness; bulbar signs; fasciculations in skelet al muscles; subtle signs of endocrine dysfunction, such as diabetes, gynecomastia, or testicular atrophy; and oligospermia. The progression is very slow, and these patients can expect a normal lifespan; it is essential to distinguish this syndrome from other, often more severe neurologic diseases.
REFERENCE
Jordan CL, Lieberman AP. Spinal and bulbar muscular atrophy: A motoneuron or muscle disease? Curr Opin Pharmacol. 2008;8(6):752–758.
XX GONADAL DYSGENESIS (46, XX)
DESCRIPTION Clinically, patients present with primary amenorrhea and lack of secondary sexual characteristics. This presentation is consistent with ovarian failure and may be associated with a host of X-chromosome aberrations. Specifically, 46, XX gonadal dysgenesis is marked by normal female chromosome constitution and hypergonadotropic hypergonadism with concurrent ovarian failure. Etiologies may be sporadic or inherited, but the condition is rarely linked to other somatic abnormalities. Other clinical manifestations include short stature, episodic metabolic acidosis, and normal intelligence.
SYNONYMS
• Ovarian failure
• Ovarian dysgenesis
• Streak ovaries
REFERENCE
Hisama FM, Zemel S, Cherniske EM, et al. 46, XX gonadal dysgenesis, short stature and recurrent metabolic acidosis in two sisters. Am J Med Genetics. 2001;98:121–124.
XX MALE REVERSAL SYNDROME (XX MALE)
DESCRIPTION A rare disorder of phenotypic males who have a 46, XX karyotype. Physical exam may reveal short stature; small, firm testes; a small- to normal-sized penis; hypospadias; and gynecomastia. Azoospermia is typical. Seminiferous tubule sclerosis can be shown on testicular biopsy. Lab investigation reveals high gonadotropin levels and decreased testosterone levels. In most cases, DNA fragments from the short arm of the Y chromosome can be detected in the distal end of the short arm of the X chromosome.
REFERENCE
Petit C, de la Chapelle A, Levilliers J, et al. An abnormal terminal X-Y interchange accounts for most but not all cases of human XX maleness. Cell. 1987;49:595.
XXX SYNDROME (TRIPLE X SYNDROME, TRIPLO-X)
DESCRIPTION Triple X chromosome abnormality occurs in ∼1.2 in 1,000 liveborn females. There are no specific diagnostic features. Menstrual irregularities and mental retardation have been reported. Fertility is usually preserved, and many XXX females have normal offspring.
REFERENCE
Sills JA, Brown JK, Grace E, et al. XXX syndrome associated with immunoglobulin deficiency and epilepsy. J Pediatr. 1978;93:469.
XXXY SYNDROME
DESCRIPTION Rare variant of Klinefelter syndrome (47, XXY), with an additional X chromosome (48, XXXY). Phenotype is similar to 47, XXY, with more pronounced features; these patients frequently exhibit microphallus, hypoplastic testicles, cryptorchidism, hypospadias, and gynecomastia. They are infertile (azoospermia), usually are mentally retarded, and have characteristic facies.
TREATMENT
Supplemental testosterone may be beneficial for virilization at puberty.
REFERENCE
Linden MG, Bender BG, Robinson A. Sex chromosome tetrasomy and pentasomy. Pediatrics. 1995;96(4 Pt 1):672–682.
XXY SYNDROME (KLINEFELTER SYNDROME)
DESCRIPTION A syndrome characterized by the presence of an extra X chromosome (usually 47 XXY), resulting in a hypogonadal male. It is the most common chromosomal aberration among men, with an estimated frequency of 1:500 among newborns. Caused by a nondisjunction of the meiotic chromosomes of the gametes from either parent, affected individuals are tall, with a eunuchoid habitus, small firm testes, and gynecomastia. Mental retardation and psychiatric disturbances have also been identified. Elevated gonadotropins and azoospermia are typically present. Seminiferous tubular sclerosis is a common finding on testicular biopsy. The diagnosis may be made with a chromatin-positive buccal smear, indicating the presence of an extra X chromosome. Karyotypes usually demonstrate 47, XXY or the milder mosaic pattern, 46, XY, 47, XXY.
TREATMENT
• No therapy improves spermatogenesis in Klinefelter syndrome.
• In mosaic Klinefelter syndrome with severe oligospermia, intracytoplasmic injection with IVF is technically possible.
REFERENCES
Klinefelter HG Jr., et al. Syndrome characterized by gynecomastia, aspermatogenesis without aleydigism and increased secretion of follicle stimulating hormone. J Clin Endocrinol. 1942;2:615.
Paduch DA, Fine RG, Bolyakov A, et al. New concepts in Klinefelter syndrome. Curr Opin Urol. 2008;18(6):621–627.