A novel TRPS1 gene mutation causing trichorhinophalangeal syndrome with growth hormone responsive short stature: a case report and review of the literature

International Journal of Pediatric Endocrinology

Doris Fadoju¹  Andrew B Muir¹  John S Parks¹  Lina Merjaneh¹ 

[1] Division of Endocrinology and Diabetes, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA

关键词: Nonsense mutation;    Missense mutation;    Hip dysplasia;    Sparse eyebrows;    Conical epiphyses;    TRPS1;    Growth hormone;    Trichorhinophalangeal syndrome type I;   

Others  :  1135810
DOI  :  10.1186/1687-9856-2014-16

 received in 2014-04-22, accepted in 2014-06-20,  发布年份 2014

【 摘 要 】

The role of growth hormone (GH) and its therapeutic supplementation in the trichorhinophalangeal syndrome type I (TRPS I) is not well delineated. TRPS I is a rare congenital syndrome, characterized by craniofacial and skeletal malformations including short stature, sparse, thin scalp hair and lateral eyebrows, pear-shaped nose, cone shaped epiphyses and hip dysplasia. It is inherited in an autosomal dominant manner and caused by haploinsufficiency of the TRPS1 gene. We report a family (Mother and 3 of her 4 children) with a novel mutation in the TRPS1 gene. The diagnosis was suspected only after meeting all family members and comparing affected and unaffected siblings since the features of this syndrome might be subtle. The eldest sibling, who had neither GH deficiency nor insensitivity, improved his growth velocity and height SDS after 2 years of treatment with exogenous GH. No change in growth velocity was observed in the untreated siblings during this same period. This report emphasizes the importance of examining all family members when suspecting a genetic syndrome. It also demonstrates the therapeutic effect of GH treatment in TRPS I despite normal GH-IGF1 axis. A review of the literature is included to address whether TRPS I is associated with: a) GH deficiency, b) GH resistance, or c) GH-responsive short stature. More studies are needed before recommending GH treatment for TRPS I but a trial should be considered on an individual basis.

【 授权许可】

   
2014 Merjaneh et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Klingmuller G: Uber eigenturmliche Konstitutionsanomalien bei 2 Schwestern und ihre Beziehung zu neuren entwicklungspathologischen Befunden. Hautarzt 1956, 7:10513.
• [2]Giedion A: Das tricho-rhino-phalangeale Syndrom. Helv Paediatr Acta 1966, 21(5):475-482.
• [3]Noltorp S, Kristoffersson UL, Mandahl N, Stigsson L, Svensson B, Werner CO: Trichorhinophalangeal syndrome type I: symptoms and signs, radiology and genetics. Ann Rheum Dis 1986, 45(1):31-36.
• [4]Giedion A, Burdea M, Fruchter Z, Meloni T, Trosc V: Autosomal- dominant transmission of the trichorhinophalangeal syndrome: report of 4 unrelated families, review of 60 cases. Helv Paediatr Acta 1973, 28:249-259.
• [5]Ludecke H-J, Wagner MJ, Nardmann J, La Pillo B, Parrish JE, Willems PJ, Haan EA, Frydman M, Hamers GJH, Wells DE, Horsthemke B: Molecular dissection of a contiguous gene syndrome: localization of the genes involved in the Langer-Giedion syndrome. Hum Mol Genet 1995, 4:31-36.
• [6]Hou J, Parrish J, Ludecke H-J, Sapru M, Wang Y, Chen W, Hill A, Siegel-Bartelt J, Northrup H, Elder FFB, Chinault C, Horsthemke B, Wagner MJ, Wells DE: A 4-megabase YAC contig that spans the Langer-Giedion syndrome region on human chromosome 8q24.1: use in refining the location of the trichorhinophalangeal syndrome and multiple exostoses genes (TRPS1 and EXT1). Genomics 1995, 29:87-97.
• [7]Napierala D, Sam K, Morello R, Zheng Q, Munivez E, Shivdasani RA, Lee B: Uncoupling of chondrocyte differentiation and perichondrial mineralization underlies the skeletal dysplasia in tricho-rhino-phalangeal syndrome. Hum Mol Genet 2008, 17:2244-2254.
• [8]Kaiser FJ, Tavassoli K, Van den Bemd G-J, Chang GTG, Horsthemke B, Moroy T, Ludecke H-J: Nuclear interaction of the dynein light chain LC8a with the TRPS1 transcription factor suppresses the transcriptional repression activity of TRPS1. Hum Mol Genet 2003, 12:1349-1358.
• [9]Momeni P, Glockner G, Schmidt O, von Holtum D, Albrecht B, Gillessen-Kaesbach G, Hennekam R, Meinecke P, Zabel B, Rosenthal A, Horsthemke B, Ludecke H-J: Mutations in a new gene, encoding a zinc-finger protein, cause tricho-rhino-phalangeal syndrome type I. Nat Genet 2000, 24:71-74.
• [10]Lüdecke HJ, Schaper J, Meinecke P, Momeni P, Gross S, von Holtum D, Hirche H, Abramowicz MJ, Albrecht B, Apacik C, Christen HJ, Claussen U, Devriendt K, Fastnacht E, Forderer A, Friedrich U, Goodship TH, Greiwe M, Hamm H, Hennekam RC, Hinkel GK, Hoeltzenbein M, Kayserili H, Majewski F, Mathieu M, McLeod R, Midro AT, Moog U, Nagai T, Niikawa N, et al.: Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III. Am J Hum Genet 2001, 68:81-91.
• [11]Naselli A, Vignolo M, Di Battista E, Papale V, Aicardi G, Becchetti S, Toma P: Trichorhinophalangeal syndrome type I in monozygotic twins discordant for hip pathology. Report on the morphological evolution of coneshaped epiphyses and the unusual pattern of skeletal maturation. Pediatr Radiol 1998, 28(11):851-855.
• [12]Sohn YB, Ki CS, Park SW, Cho SY, Ko AR, Kwon MJ, Kim JY, Park HD, Kim OH, Jin DK: Clinical, biochemical, and genetic analysis of two korean patients with trichorhinophalangeal syndrome type I and growth hormone deficiency. Ann Clin Lab Sci 2012, 42(3):307-312.
• [13]Stagi S, Bindi G, Galluzzi F, Lapi E, Salti R, Chiarelli F: Partial growth hormone deficiency and changed bone quality and mass in type I trichorhinophalangeal syndrome. Am J Med Genet A 2008, 146A(12):1598-1604. Erratum in: Am J Med Genet A 2009 Feb: 149A (2): 296
• [14]Sarafoglou K, Moassesfar S, Miller BS: Improved growth and bone mineral density in type I trichorhinophalangeal syndrome in response to growth hormone therapy. Clin Genet 2010, 78:591-593.
• [15]Gai Z, Gui T, Muragaki Y: The function of TRPS1 in the development and differentiation of bone, kidney, and hair follicles. Histol Histopathol 2011, 26:915-921.
• [16]Wuelling M, Pasdziernik M, Moll CN, Thiesen AM, Schneider S, Johannes C, Vortkamp A: The multi zinc-finger protein Trps1 acts as a regulator of histone deacetylation during mitosis. Cell Cycle 2013, 12(14):2219-2232.
• [17]Kaiser FJ, Brega P, Raff ML, Byers PH, Gallati S, Kay TT, De Almeida S, Horsthemke B, Ludecke HJ: Novel missense mutations in the TRPS1 transcription factor define the nuclear localization signal. Eur J Hum Genet 2004, 12:121-126.
• [18]Malik TH, Shoichet SA, Latham P, Kroll TG, Peters LL, Shivdasani RA: Transcriptional repression and developmental functions of atypical vertebrate GATA protein TRPS1. EMBO J 2001, 20:1715-1725.
• [19]Hilczer M, Smyczyńska J, Lewinski A: Limitations of clinical utility of growth hormone stimulating tests in diagnosing children with short stature. Endocr Regul 2006, 40:69-75.
• [20]Tenenbaum-Rakover Y: The need to revise the cut-off level for the diagnosis of GH deficiency in children. Pediatr Endocrinol Rev 2008, 5(4):880-888.
• [21]Rose SR, Ross JL, Uriarte M, Barnes KM, Cassorla FG, Cutler GB Jr: The advantage of measuring stimulated as compared with spontaneous growth hormone levels in the diagnosis of growth hormone deficiency. N Engl J Med 1988, 319(4):201-207.
• [22]Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM: Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab 2013, 2008:4210-4217. doi: 10.1210/jc.2008-0509
• [23]Zhang Y, Xie RL, Gordon J, LeBlanc K, Stein JL, Lian JB, Van Wijnen AJ, Stein GS: Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. J Biol Chem 2012, 287:21926-21935.
• [24]Stabler B, Clopper RR, Siegel PT, Stoppani C, Compton PG, Underwood LE: Academic achievement and psychological adjustment in short children: the National Cooperative Growth Study. J Dev Behav Pediatr 1994, 15:1-6.
• [25]Steinhausen HC, Dorr HG, Kannenberg R, Malin Z: The behavior profile of children and adolescents with short stature. J Dev Behav Pediatr 2000, 21:423-428.
• [26]Takano K, Tanaka T, Saito T, Committee for the Study Group of Adult GH Deficiency: Psychosocial adjustment in a large cohort of adults with growth hormone deficiency treated with growth hormone in childhood: summary of a questionnaire survey. Acta Paediatr Scand Suppl 1994, 399:16-19.