Abstract
Kabuki syndrome is characterized by distinctive facial features, multiple anomalies and mental retardation. In this syndrome, structural CNS abnormalities are commonly observed, but congenital abnormalities in the pituitary gland or hypothalamus have rarely been reported. We searched the published medical literature on the complications in hypothalamic pituitary axis in this syndrome. As a result, only nine patients with Kabuki syndrome had been reported to have complications in hypothalamic pituitary axis in previous papers. Among the nine reported patients and one presented case in this report, GH deficiency was the most frequent complication and found in six patients. Precocious puberty and central diabetes insipidus (DI) was identified in two cases, respectively, and ACTH deficiency was found in one. One case had combination of GH deficiency and central DI. Three of the 10 patients demonstrated abnormal pituitary findings in MRI study. Two of the six patients with GH deficiency were accompanied with premature thelarche. This review highlights that patients with Kabuki syndrome could present various clinical manifestations due to abnormalities in hypothalamic pituitary axis.
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Abbreviations
- AVP:
-
Arginine-vasopressin
- CNS:
-
Central nervous system
- DDAVP:
-
1-deamino-8-d-arginine vasopressin
- DI:
-
Diabetes insipidus
- eGFR:
-
Estimated glomerular filtration rate
- GH:
-
Growth hormone
- MLL:
-
Mixed lineage leukemia
- MRI:
-
Magnetic resonance imaging
References
Niikawa N, Matsuura N, Fukushima Y, Ohsawa T, Kajii T (1981) Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency. J Pediatr 99(4):565–569
Kuroki Y, Suzuki Y, Chyo H, Hata A, Matsui I (1981) A new malformation syndrome of long palpebral fissures, large ears, depressed nasal tip, and skeletal anomalies associated with postnatal dwarfism and mental retardation. J Pediatr 99(4):570–573
Ben-Omran T, Teebi AS (2005) Structural central nervous system (CNS) anomalies in Kabuki syndrome. Am J Med Genet A 137(1):100–103
Tawa R, Kaino Y, Ito T, Goto Y, Kida K, Matsuda H (1994) A case of Kabuki make-up syndrome with central diabetes insipidus and growth hormone neurosecretory dysfunction. Acta Paediatr Jpn 36(4):412–415
Niikawa N, Kuroki Y, Kajii T, Matsuura N, Ishikiriyama S, Tonoki H, Ishikawa N, Yamada Y, Fujita M, Umemoto H et al (1988) Kabuki make-up (Niikawa-Kuroki) syndrome: a study of 62 patients. Am J Med Genet 31(3):565–589
Ma KH, Chow SN, Yau FT (2005) Isolated adrenocorticotropin deficiency in a child with Kabuki syndrome. J Pediatr Endocrinol Metab 18(6):607–609
Kuroki Y, Katsumata N, Eguchi T, Fukushima Y, Suwa S, Kajii T (1987) Precocious puberty in Kabuki makeup syndrome. J Pediatr 110(5):750–752
Handa Y, Maeda K, Toida M, Kitajima T, Ishimaru J, Nagai A, Oka N (1991) Kabuki make-up syndrome (Niikawa-Kuroki syndrome) with cleft lip and palate. J Craniomaxillofac Surg 19(3):99–101
Gabrielli O, Bruni S, Bruschi B, Carloni I, Coppa GV (2002) Kabuki syndrome and growth hormone deficiency: description of a case treated by long-term hormone replacement. Clin Dysmorphol 11(1):71–72
Franceschini P, Vardeu MP, Guala A, Franceschini D, Testa A, Corrias A, Chiabotto P (1993) Lower lip pits and complete idiopathic precocious puberty in a patient with Kabuki make-up (Niikawa-Kuroki) syndrome. Am J Med Genet 47(3):423–425
Devriendt K, Lemli L, Craen M, de Zegher F (1995) Growth hormone deficiency and premature thelarche in a female infant with kabuki makeup syndrome. Horm Res 43(6):303–306
Satoh M, Arakawa K, Yokoya S, Morooka K (1993) A case of Kabuki make-up syndrome associated with growth hormone deficiency. Clin Pediatr Endocrinol 2(1):13–16
Kawame H, Hannibal MC, Hudgins L, Pagon RA (1999) Phenotypic spectrum and management issues in Kabuki syndrome. J Pediatr 134(4):480–485
Argyropoulou MI, Kiortsis DN (2005) MRI of the hypothalamic-pituitary axis in children. Pediatr Radiol 35(11):1045–1055
Ghirardello S, Garre ML, Rossi A, Maghnie M (2007) The diagnosis of children with central diabetes insipidus. J Pediatr Endocrinol Metab 20(3):359–375
Adam MP, Hudgins L (2005) Kabuki syndrome: a review. Clin Genet 67(3):209–219
Matsumoto N, Niikawa N (2003) Kabuki make-up syndrome: a review. Am J Med Genet C Semin Med Genet 117C(1):57–65
Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J (2010) Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet 42(9):790–793
Hannibal MC, Buckingham KJ, Ng SB, Ming JE, Beck AE, McMillin MJ, Gildersleeve HI, Bigham AW, Tabor HK, Mefford HC, Cook J, Yoshiura K, Matsumoto T, Matsumoto N, Miyake N, Tonoki H, Naritomi K, Kaname T, Nagai T, Ohashi H, Kurosawa K, Hou JW, Ohta T, Liang D, Sudo A, Morris CA, Banka S, Black GC, Clayton-Smith J, Nickerson DA, Zackai EH, Shaikh TH, Donnai D, Niikawa N, Shendure J, Bamshad MJ (2011) Spectrum of MLL2 (ALR) mutations in 110 cases of Kabuki syndrome. Am J Med Genet A 155A(7):1511–1516
Li Y, Bogershausen N, Alanay Y, Simsek Kiper PO, Plume N, Keupp K, Pohl E, Pawlik B, Rachwalski M, Milz E, Thoenes M, Albrecht B, Prott EC, Lehmkuhler M, Demuth S, Utine GE, Boduroglu K, Frankenbusch K, Borck G, Gillessen-Kaesbach G, Yigit G, Wieczorek D, Wollnik B (2011) A mutation screen in patients with Kabuki syndrome. Hum Genet 130(6):715–724
Micale L, Augello B, Fusco C, Selicorni A, Loviglio MN, Silengo MC, Reymond A, Gumiero B, Zucchetti F, D’Addetta EV, Belligni E, Calcagni A, Digilio MC, Dallapiccola B, Faravelli F, Forzano F, Accadia M, Bonfante A, Clementi M, Daolio C, Douzgou S, Ferrari P, Fischetto R, Garavelli L, Lapi E, Mattina T, Melis D, Patricelli MG, Priolo M, Prontera P, Renieri A, Mencarelli MA, Scarano G, Monica MD, Toschi B, Turolla L, Vancini A, Zatterale A, Gabrielli O, Zelante L, Merla G (2011) Mutation spectrum of MLL2 in a cohort of kabuki syndrome patients. Orphanet J Rare Dis 6:38
Paulussen AD, Stegmann AP, Blok MJ, Tserpelis D, Posma-Velter C, Detisch Y, Smeets EE, Wagemans A, Schrander JJ, van den Boogaard MJ, van der Smagt J, van Haeringen A, Stolte-Dijkstra I, Kerstjens-Frederikse WS, Mancini GM, Wessels MW, Hennekam RC, Vreeburg M, Geraedts J, de Ravel T, Fryns JP, Smeets HJ, Devriendt K, Schrander-Stumpel CT (2011) MLL2 mutation spectrum in 45 patients with Kabuki syndrome. Hum Mutat 32(2):E2018–E2025
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Ito, N., Ihara, K., Tsutsumi, Y. et al. Hypothalamic pituitary complications in Kabuki syndrome. Pituitary 16, 133–138 (2013). https://doi.org/10.1007/s11102-012-0386-8
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DOI: https://doi.org/10.1007/s11102-012-0386-8