Further delineation of Malan syndrome

Manuela Priolo, Denny Schanze, Katrin Tatton-Brown, Paul A. Mulder, Jair Tenorio, Kreepa Kooblall, Inés Hernández Acero, Fowzan S. Alkuraya, Pedro Arias, Laura Bernardini, Emilia K. Bijlsma, Trevor Cole, Christine Coubes, Irene Dapia, Sally Davies, Nataliya Di Donato, Nursel H. Elcioglu, Jill Ann Fahrner, Alison Foster, Noelia García González & 34 others Ilka Huber, Maria Iascone, Ann Sophie Kaiser, Arveen Kamath, Jan Liebelt, Sally Ann Lynch, Saskia M. Maas, Corrado Mammì, Inge B. Mathijssen, Shane McKee, Leonie A. Menke, Ghayda M. Mirzaa, Tara Montgomery, Dorothee Neubauer, Thomas E. Neumann, Letizia Pintomalli, Maria Antonietta Pisanti, Astrid S. Plomp, Sue Price, Claire Salter, Fernando Santos-Simarro, Pierre Sarda, Mabel Segovia, Charles Shaw-Smith, Sarah Smithson, Mohnish Suri, Rita Maria Valdez, Arie Van Haeringen, Johanna M. Van Hagen, Marcela Zollino, Pablo Lapunzina, Rajesh V. Thakker, Martin Zenker, Raoul C. Hennekam

Research output: Contribution to journalArticle

Abstract

Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip, and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall–Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only.

Original languageEnglish (US)
Pages (from-to)1226-1237
Number of pages12
JournalHuman Mutation
Volume39
Issue number9
DOIs
StatePublished - Sep 1 2018

Fingerprint

Sotos Syndrome
Megalencephaly
Chin
Forehead
Terminator Codon
Sequence Deletion
Genetic Association Studies
Lip
Point Mutation
Intellectual Disability
Exons
Epilepsy
Anxiety
Phenotype
Weaver syndrome
Marshall-Smith syndrome

Keywords

  • Malan syndrome
  • Marshall-Smith syndrome
  • NFIX
  • phenotype
  • phenotype-genotype
  • Sotos syndrome
  • Weaver syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Priolo, M., Schanze, D., Tatton-Brown, K., Mulder, P. A., Tenorio, J., Kooblall, K., ... Hennekam, R. C. (2018). Further delineation of Malan syndrome. Human Mutation, 39(9), 1226-1237. https://doi.org/10.1002/humu.23563

Further delineation of Malan syndrome. / Priolo, Manuela; Schanze, Denny; Tatton-Brown, Katrin; Mulder, Paul A.; Tenorio, Jair; Kooblall, Kreepa; Acero, Inés Hernández; Alkuraya, Fowzan S.; Arias, Pedro; Bernardini, Laura; Bijlsma, Emilia K.; Cole, Trevor; Coubes, Christine; Dapia, Irene; Davies, Sally; Di Donato, Nataliya; Elcioglu, Nursel H.; Fahrner, Jill Ann; Foster, Alison; González, Noelia García; Huber, Ilka; Iascone, Maria; Kaiser, Ann Sophie; Kamath, Arveen; Liebelt, Jan; Lynch, Sally Ann; Maas, Saskia M.; Mammì, Corrado; Mathijssen, Inge B.; McKee, Shane; Menke, Leonie A.; Mirzaa, Ghayda M.; Montgomery, Tara; Neubauer, Dorothee; Neumann, Thomas E.; Pintomalli, Letizia; Pisanti, Maria Antonietta; Plomp, Astrid S.; Price, Sue; Salter, Claire; Santos-Simarro, Fernando; Sarda, Pierre; Segovia, Mabel; Shaw-Smith, Charles; Smithson, Sarah; Suri, Mohnish; Valdez, Rita Maria; Van Haeringen, Arie; Van Hagen, Johanna M.; Zollino, Marcela; Lapunzina, Pablo; Thakker, Rajesh V.; Zenker, Martin; Hennekam, Raoul C.

In: Human Mutation, Vol. 39, No. 9, 01.09.2018, p. 1226-1237.

Research output: Contribution to journalArticle

Priolo, M, Schanze, D, Tatton-Brown, K, Mulder, PA, Tenorio, J, Kooblall, K, Acero, IH, Alkuraya, FS, Arias, P, Bernardini, L, Bijlsma, EK, Cole, T, Coubes, C, Dapia, I, Davies, S, Di Donato, N, Elcioglu, NH, Fahrner, JA, Foster, A, González, NG, Huber, I, Iascone, M, Kaiser, AS, Kamath, A, Liebelt, J, Lynch, SA, Maas, SM, Mammì, C, Mathijssen, IB, McKee, S, Menke, LA, Mirzaa, GM, Montgomery, T, Neubauer, D, Neumann, TE, Pintomalli, L, Pisanti, MA, Plomp, AS, Price, S, Salter, C, Santos-Simarro, F, Sarda, P, Segovia, M, Shaw-Smith, C, Smithson, S, Suri, M, Valdez, RM, Van Haeringen, A, Van Hagen, JM, Zollino, M, Lapunzina, P, Thakker, RV, Zenker, M & Hennekam, RC 2018, 'Further delineation of Malan syndrome', Human Mutation, vol. 39, no. 9, pp. 1226-1237. https://doi.org/10.1002/humu.23563
Priolo M, Schanze D, Tatton-Brown K, Mulder PA, Tenorio J, Kooblall K et al. Further delineation of Malan syndrome. Human Mutation. 2018 Sep 1;39(9):1226-1237. https://doi.org/10.1002/humu.23563
Priolo, Manuela ; Schanze, Denny ; Tatton-Brown, Katrin ; Mulder, Paul A. ; Tenorio, Jair ; Kooblall, Kreepa ; Acero, Inés Hernández ; Alkuraya, Fowzan S. ; Arias, Pedro ; Bernardini, Laura ; Bijlsma, Emilia K. ; Cole, Trevor ; Coubes, Christine ; Dapia, Irene ; Davies, Sally ; Di Donato, Nataliya ; Elcioglu, Nursel H. ; Fahrner, Jill Ann ; Foster, Alison ; González, Noelia García ; Huber, Ilka ; Iascone, Maria ; Kaiser, Ann Sophie ; Kamath, Arveen ; Liebelt, Jan ; Lynch, Sally Ann ; Maas, Saskia M. ; Mammì, Corrado ; Mathijssen, Inge B. ; McKee, Shane ; Menke, Leonie A. ; Mirzaa, Ghayda M. ; Montgomery, Tara ; Neubauer, Dorothee ; Neumann, Thomas E. ; Pintomalli, Letizia ; Pisanti, Maria Antonietta ; Plomp, Astrid S. ; Price, Sue ; Salter, Claire ; Santos-Simarro, Fernando ; Sarda, Pierre ; Segovia, Mabel ; Shaw-Smith, Charles ; Smithson, Sarah ; Suri, Mohnish ; Valdez, Rita Maria ; Van Haeringen, Arie ; Van Hagen, Johanna M. ; Zollino, Marcela ; Lapunzina, Pablo ; Thakker, Rajesh V. ; Zenker, Martin ; Hennekam, Raoul C. / Further delineation of Malan syndrome. In: Human Mutation. 2018 ; Vol. 39, No. 9. pp. 1226-1237.
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AU - Acero, Inés Hernández

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AU - Liebelt, Jan

AU - Lynch, Sally Ann

AU - Maas, Saskia M.

AU - Mammì, Corrado

AU - Mathijssen, Inge B.

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AU - Montgomery, Tara

AU - Neubauer, Dorothee

AU - Neumann, Thomas E.

AU - Pintomalli, Letizia

AU - Pisanti, Maria Antonietta

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