Microcephaly, dysmorphic features, corneal dystrophy, hairy nipples, underdeveloped labioscrotal folds, and small cerebellum in four patients

American Journal of Medical Genetics, Part A

Volumn 170, Issue 6, 2016, Pages 1391-1399

  Kayserili, Hülya ^a,b   Altunoglu, Umut ^b   Yesil, Gozde ^c   Rosti, Rasim Özgür ^b,d  

^a KOÇ UNIVERSITY   (Turkey)

^b ISTANBUL UNIVERSITY   (Turkey)

^c BEZMIALEM VAKIF UNIVERSITY   (Turkey)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Corneal dystrophy; Hairy nipples; Pontocerebellar hypoplasia; Scrotal labial aplasia; Underdeveloped labioscrotal folds

Indexed keywords

TESTOSTERONE; BIOLOGICAL MARKER;

ARTICLE; AUTOSOMAL RECESSIVE INHERITANCE; CATARACT EXTRACTION; CEREBELLUM ATROPHY; CEREBELLUM HYPOPLASIA; CESAREAN SECTION; CHILD; CLINICAL ARTICLE; CONSANGUINITY; CORNEA DYSTROPHY; CORNEA ULCER; DANDY WALKER SYNDROME; DENVER DEVELOPMENTAL SCREENING TEST; DEVELOPMENTAL DISORDER; DIARRHEA; ELECTROENCEPHALOGRAPHY; FACE DYSMORPHIA; FEMALE; FETUS DISTRESS; FEVER; GENITAL MALFORMATION; HAIRY NIPPLE; HUMAN; INFANT; KERATITIS; KERATOPLASTY; MALE; MENINGOENCEPHALITIS; MICROCEPHALY; NEWBORN; NIPPLE MALFORMATION; NUCLEAR MAGNETIC RESONANCE IMAGING; OSTEOPENIA; PRESCHOOL CHILD; PRIORITY JOURNAL; SCHOOL CHILD; SPECIAL EDUCATION; TESTOSTERONE BLOOD LEVEL; UNDERDEVELOPED LABIOSCROTAL FOLD; VOMITING; ABNORMALITIES; ABNORMALITIES, MULTIPLE; BRAIN; CASE REPORT; CEREBELLUM; CORNEAL DYSTROPHIES, HEREDITARY; DEVELOPMENTAL DISABILITIES; DIAGNOSTIC IMAGING; FACIES; GENETIC SCREENING; METABOLISM; NERVOUS SYSTEM MALFORMATIONS; PEDIGREE; PHENOTYPE; SYNDROME;

ABNORMALITIES, MULTIPLE; BIOMARKERS; BRAIN; CEREBELLUM; CHILD; CHILD, PRESCHOOL; CONSANGUINITY; CORNEAL DYSTROPHIES, HEREDITARY; DEVELOPMENTAL DISABILITIES; DIAGNOSTIC IMAGING; FACIES; FEMALE; GENETIC TESTING; HUMANS; INFANT; MALE; MICROCEPHALY; NERVOUS SYSTEM MALFORMATIONS; PEDIGREE; PHENOTYPE; SYNDROME;

EID: 84963815773     PISSN: 15524825     EISSN: 15524833     Source Type: Journal    
DOI: 10.1002/ajmg.a.37652     Document Type: Article

References (50)

1. Akizu N, Cantagrel V, Schroth J, Cai N, Vaux K, McCloskey D, Naviaux RK, Van Vleet J, Fenstermaker AG, Silhavy JL, Scheliga JS, Toyama K, Morisaki H, Sonmez FM, Celep F, Oraby A, Zaki MS, Al-Baradie R, Faqeih EA, Saleh MA, Spencer E, Rosti RO, Scott E, Nickerson E, Gabriel S, Morisaki T, Holmes EW, Gleeson JG. 2013. AMPD2 regulates GTP synthesis and is mutated in a potentially treatable neurodegenerative brainstem disorder. Cell 154:505-517.
2. Albrecht S, Schneider MC, Belmont J, Armstrong DL. 1993. Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly. Acta Neuropathol 85:394-399.
3. Anderson C, Davies JH, Lamont L, Foulds N. 2011. Early pontocerebellar hypoplasia with vanishing testes: A new syndrome? Am J Med Genet Part A 155A:667-672.
4. Arts WF, Hofstee Y, Drejer GF, Beverstock GC, Oosterwijk JC. 1995. Cerebellar and brainstem hypoplasia in a child with a partial monosomy for the short arm of chromosome 5 and partial trisomy for the short arm of chromosome 10. Neuropediatrics 26:41-44.
5. Bamshad M, Le T, Watkins WS, Dixon ME, Kramer BE, Roeder AD, Carey JC, Root S, Schinzel A, Van Maldergem L, Gardner RJ, Lin RC, Seidman CE, Seidman JG, Wallerstein R, Moran E, Sutphen R, Campbell CE, Jorde LB. 1999. The spectrum of mutations in TBX3: Genotype/phenotype relationship in ulnar-mammary syndrome. Am J Hum Genet 64:1550-1562.
6. Barth PG. 1993. Pontocerebellar hypoplasias. An overview of a group of inherited neurodegenerative disorders with fetal onset. Brain Dev 15:411-422.
7. Barth PG. 2000. Pontocerebellar hypoplasia-how many types? Eur J Paediatr Neurol 4:161-162.
8. Barth PG, Blennow G, Lenard HG, Begeer JH, van der Kley JM, Hanefeld F, Peters AC, Valk J. 1995. The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2): Compiled data from 10 pedigrees. Neurology 45:311-317.
9. Botchkarev VA, Botchkareva NV, Roth W, Nakamura M, Chen LH, Herzog W, Lindner G, McMahon JA, Peters C, Lauster R, McMahon AP, Paus R. 1999. Noggin is a mesenchymally derived stimulator of hair-follicle induction. Nat Cell Biol 1:158-164.
10. Botchkarev VA, Botchkareva NV, Sharov AA, Funa K, Huber O, Gilchrest BA. 2002. Modulation of BMP signaling by noggin is required for induction of the secondary (nontylotrich) hair follicles. J Invest Dermatol 118:3-10.
11. Boycott KM, Flavelle S, Bureau A, Glass HC, Fujiwara TM, Wirrell E, Davey K, Chudley AE, Scott JN, McLeod DR, Parboosingh JS. 2005. Homozygous deletion of the very low density lipoprotein receptor gene causes autosomal recessive cerebellar hypoplasia with cerebral gyral simplification. Am J Hum Genet 77:477-483.
12. Budde BS, Namavar Y, Barth PG, Poll-The BT, Nürnberg G, Becker C, van Ruissen F, Weterman MA, Fluiter K, te Beek ET, Aronica E, van der Knaap MS, Höhne W, Toliat MR, Crow YJ, Steinling M, Voit T, Roelenso F, Brussel W, Brockmann K, Kyllerman M, Boltshauser E, Hammersen G, Willemsen M, Basel-Vanagaite L, Krägeloh-Mann I, de Vries LS, Sztriha L, Muntoni F, Ferrie CD, Battini R, Hennekam RC, Grillo E, Beemer FA, Stoets LM, Wollnik B, Nürnberg P, Baas F. 2008. TRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. Nat Genet 40:1113-1118.
13. Cassandrini D, Cilio MR, Bianchi M, Doimo M, Balestri M, Tessa A, Rizza T, Sartori G, Meschini MC, Nesti C, Tozzi G, Petruzzella V, Piemonte F, Bisceglia L, Bruno C, Dionisi-Vici C, D'Amico A, Fattori F, Carrozzo R, Salviati L, Santorelli FM, Bertini E. 2013. Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: Definition of the clinical spectrum and molecular findings in five patients. J Inherit Metab Dis 36:43-53.
14. Chandramouli A, Hatsell SJ, Pinderhughes A, Koetz L, Cowin P. 2013. Gli activity is critical at multiple stages of embryonic mammary and nipple development. PLoS ONE 8:e79845.
15. Cho KW, Kim JY, Song SJ, Farrell E, Eblaghie MC, Kim HJ, Tickle C, Jung HS. 2006. Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development. Proc Natl Acad Sci USA 103:16788-16793.
16. Cormand B, Pihko H, Bayés M, Valanne L, Santavuori P, Talim B, Gershoni-Baruch R, Ahmad A, van Bokhoven H, Brunner HG, Voit T, Topaloglu H, Dobyns WB, Lehesjoki AE. 2001. Clinical and genetic distinction between Walker-Warburg syndrome and muscle-eye-brain disease. Neurology 56:1059-1069.
17. Dancourt J, Vuillaumier-Barrot S, de Baulny HO, Sfaello I, Barnier A, le Bizec C, Dupre T, Durand G, Seta N, Moore SE. 2006. A new intronic mutation in the DPM1 gene is associated with a milder form of CDG Ie in two French siblings. Pediatr Res 59:835-839.
18. Der Kaloustian VM, Jarudi NI, Khoury MJ, Afifi AK, Bahuth NB, Deeb ME, Shammas J, Mikati MA. 1985. Familial spinocerebellar degeneration with corneal dystrophy. Am J Med Genet 20:325-339.
19. Durmaz B, Wollnik B, Cogulu O, Li Y, Tekgul H, Hazan F, Ozkinay F. 2009. Pontocerebellar hypoplasia type III (CLAM): Extended phenotype and novel molecular findings. J Neurol 256:416-419.
20. Eastwood J, Offutt C, Menon K, Keel M, Hrncirova P, Novotny MV, Arnold R, Foley J. 2007. Identification of markers for nipple epidermis: Changes in expression during pregnancy and lactation. Differentiation 75:75-83.
21. Edvardson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I, Einbinder T, Saada A, Elpeleg O. 2007. Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. Am J Hum Genet 81:857-862.
22. Flum AS, Chaviano AH, Kaplan WE. 2012. Hemiscrotal agenesis: New variation in a rare anomaly. Urology 79:210-211.
23. Haraguchi R, Suzuki K, Murakami R, Sakai M, Kamikawa M, Kengaku M, Sekine K, Kawano H, Kato S, Ueno N, Yamada G. 2000. Molecular analysis of external genitalia formation: The role of fibroblast growth factor (Fgf) genes during genital tubercle formation. Development 127:2471-2479.
24. Hens JR, Dann P, Zhang JP, Harris S, Robinson GW, Wysolmerski J. 2007. BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction. Development 134:1221-1230.
25. Hong SE, Shugart YY, Huang DT, Shahwan SA, Grant PE, Hourihane JO, Martin ND, Walsh CA. 2000. Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat Genet 26:93-96.
26. Janoff DM, Skoog SJ. 2005. Congenital scrotal agenesis: Description of a rare anomaly and management strategies. J Urol 173:589-591.
27. Karaca E, Weitzer S, Pehlivan D, Shiraishi H, Gogakos T, Hanada T, Jhangiani SN, Wiszniewski W, Withers M, Campbell IM, Erdin S, Isikay S, Franco LM, Gonzaga-Jauregui C, Gambin T, Gelowani V, Hunter JV, Yesil G, Koparir E, Yilmaz S, Brown M, Briskin D, Hafner M, Morozov P, Farazi TA, Bernreuther C, Glatzel M, Trattnig S, Friske J, Kronnerwetter C, Bainbridge MN, Gezdirici A, Seven M, Muzny DM, Boerwinkle E, Ozen M, Baylor Hopkins Center for Mendelian Genomics, Clausen T, Tuschl T, Yuksel A, Hess A, Gibbs RA, Martinez J, Penninger JM, Lupski JR. 2014. Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function. Cell 157:636-650.
28. Lin C, Yin Y, Long F, Ma L. 2008. Tissue-specific requirements of beta-catenin in external genitalia development. Development 135:2815-2825.
29. Mahbubul Huq AH, Nigro MA. 2000. XY sex reversal and a nonprogressive neurologic disorder: A new syndrome? Pediatr Neurol 23:357-360.
30. Mayer JA, Foley J, De La Cruz D, Chuong CM, Widelitz R. 2008. Conversion of the nipple to hair-bearing epithelia by lowering bone morphogenetic protein pathway activity at the dermal-epidermal interface. Am J Pathol 173:1339-1348.
31. Mochida GH, Ganesh VS, de Michelena MI, Dias H, Atabay KD, Kathrein KL, Huang HT, Hill RS, Felie JM, Rakiec D, Gleason D, Hill AD, Malik AN, Barry BJ, Partlow JN, Tan WH, Glader LJ, Barkovich AJ, Dobyns WB, Zon LI, Walsh CA. 2012. CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development. Nat Genet 44:1260-1264.
32. Mohan PP, Woodward MN, Chandran H, Parashar K. 2006. Topical testosterone in scrotal agenesis. Pediatr Surg Int 22:565-566.
33. Montero M, Méndez R, Tellado M, Vela D, Pais E, Gallego M. 2001. Agenesis of the scrotum. Pediatr Dermatol 18:141-142.
34. Moog U, Kutsche K, Kortüm F, Chilian B, Bierhals T, Apeshiotis N, Balg S, Chassaing N, Coubes C, Das S, Engels H, Van Esch H, Grasshoff U, Heise M, Isidor B, Jarvis J, Koehler U, Martin T, Oehl-Jaschkowitz B, Ortibus E, Pilz DT, Prabhakar P, Rappold G, Rau I, Rettenberger G, Schlüter G, Scott RH, Shoukier M, Wohlleber E, Zirn B, Dobyns WB, Uyanik G. 2011. Phenotypic spectrum associated with CASK loss-of-function mutations. J Med Genet 48:741-751.
35. Nakamura Y, Wakitani S, Nakayama J, Wakabayashi S, Horiuchi H, Takaoka K. 2003. Temporal and spatial expression profiles of BMP receptors and noggin during BMP-2-induced ectopic bone formation. J Bone Miner Res 18:1854-1862.
36. Namavar Y, Barth PG, Poll-The BT, Baas F. 2011. Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet J Rare Dis 6:50.
37. Patel MS, Becker LE, Toi A, Armstrong DL, Chitayat D. 2006. Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5? Am J Med Genet Part A 140A:594-603.
38. Rajab A, Mochida GH, Hill A, Ganesh V, Bodell A, Riaz A, Grant PE, Shugart YY, Walsh CA. 2003. A novel form of pontocerebellar hypoplasia maps to chromosome 7q11-21. Neurology 60:1664-1667.
39. Rosti RO, Karaer K, Karaman B, Torun D, Guran S, Bahce M. 2013. Gorlin-Chaudhry-Moss syndrome revisited: Expanding the phenotype. Am J Med Genet Part A 161A:1737-1742.
40. Rudnik-Schöneborn S, Barth PG, Zerres K. 2014. Pontocerebellar hypoplasia. Am J Med Genet Part C Semin Med Genet 166C:173-183.
41. Schaffer AE, Eggens VR, Caglayan AO, Reuter MS, Scott E, Coufal NG, Silhavy JL, Xue Y, Kayserili H, Yasuno K, Rosti RO, Abdellateef M, Caglar C, Kasher PR, Cazemier JL, Weterman MA, Cantagrel V, Cai N, Zweier C, Altunoglu U, Satkin NB, Aktar F, Tuysuz B, Yalcinkaya C, Caksen H, Bilguvar K, Fu XD, Trotta CR, Gabriel S, Reis A, Gunel M, Baas F, Gleeson JG. 2014. CLP1 founder mutation links tRNA splicing and maturation to cerebellar development and neurodegeneration. Cell 157:651-663.
42. Silay MS, Yesil G, Yildiz K, Kilincaslan H, Ozgen IT, Armagan A. 2013. Congenital agenesis of scrotum and labia majora in siblings. Urology 81:421-423.
43. Siriwardena K, Al-Maawali A, Guerin A, Blaser S, Chitayat D. 2013. XY sex reversal, pontocerebellar hypoplasia and intellectual disability: Confirmation of a new syndrome. Am J Med Genet Part A 161A:1714-1717.
44. Suzuki K, Bachiller D, Chen YP, Kamikawa M, Ogi H, Haraguchi R, Ogino Y, Minami Y, Mishina Y, Ahn K, Crenshaw EB, 3rd, Yamada G. 2003. Regulation of outgrowth and apoptosis for the terminal appendage: External genitalia development by concerted actions of BMP signaling. Development 130:6209-6220.
45. Tamraz J, Rethoré MO, Lejeune J, Outin C, Goepel R, Stievenart JL, Iba-Zizen MT, Cabanis EA. 1993. [Brain morphometry using MRI in Cri-du-Chat Syndrome. Report of seven cases with review of the literature]. Ann Genet 36:75-87.
46. Verga G, Avolio L. 1996. Agenesis of the scrotum: An extremely rare anomaly. J Urol 156:1467.
47. Wilhelm D, Koopman P. 2006. The makings of maleness: Towards an integrated view of male sexual development. Nat Rev Genet 7:620-631.
48. Wright JE. 1993. Congenital absence of the scrotum: Case report and description of an original technique of construction of a scrotum. J Pediatr Surg 28:264-266.
49. Wu HJ, Easwaran T, Offutt CD, Elgar RL, Spandau DF, Koyama S, Foley J. 2015. Expansion of specialized epidermis induced by hormonal state and mechanical strain. Mech Dev 136:73-86.
50. Yamaguchi TP, Bradley A, McMahon AP, Jones S. 1999. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo. Development 126:1211-1223.