Baraitser-Winter cerebrofrontofacial syndrome: Delineation of the spectrum in 42 cases

Alain Verloes, Nataliya Di Donato, Julien Masliah-Planchon, Marjolijn Jongmans, Omar A. Abdul-Raman, Beate Albrecht, Judith Allanson, Han Brunner, Debora Bertola, Nicolas Chassaing, Albert David, Koen Devriendt, Pirayeh Eftekhari, Valérie Drouin-Garraud, Francesca Faravelli, Laurence Faivre, Fabienne Giuliano, Leina Guion Almeida, Jorge Juncos, Marlies KempersHatice Koçak Eker, Didier Lacombe, Angela Lin, Grazia Mancini, Daniela Melis, Charles Marques Lourenço, Victoria Mok Siu, Gilles Morin, Marjan Nezarati, Malgorzata J M Nowaczyk, Jeanette C. Ramer, Sara Osimani, Nicole Philip, Mary Ella Pierpont, Vincent Procaccio, Zeichi Seide Roseli, Massimiliano Rossi, Cristina Rusu, Yves Sznajer, Ludivine Templin, Vera Uliana, Mirjam Klaus, Bregje Van Bon, Conny Van Ravenswaaij, Bruce Wainer, Andrew E. Fry, Andreas Rump, Alexander Hoischen, Séverine Drunat, Jean Baptiste Rivière, William B. Dobyns, Daniela T. Pilz

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity.

Original languageEnglish (US)
Pages (from-to)292-301
Number of pages10
JournalEuropean Journal of Human Genetics
Volume23
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

Lissencephaly
Actins
Mutation
Arthrogryposis
Hallux
Hypertelorism
Coloboma
Eyebrows
Cell Physiological Phenomena
Microcephaly
Meristem
Congenital Heart Defects
Dystonia
Cleft Lip
Cleft Palate
Deafness
Iris
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Nose
Neuroimaging

Cite this

Verloes, A., Di Donato, N., Masliah-Planchon, J., Jongmans, M., Abdul-Raman, O. A., Albrecht, B., ... Pilz, D. T. (2015). Baraitser-Winter cerebrofrontofacial syndrome: Delineation of the spectrum in 42 cases. European Journal of Human Genetics, 23(3), 292-301. https://doi.org/10.1038/ejhg.2014.95

Baraitser-Winter cerebrofrontofacial syndrome : Delineation of the spectrum in 42 cases. / Verloes, Alain; Di Donato, Nataliya; Masliah-Planchon, Julien; Jongmans, Marjolijn; Abdul-Raman, Omar A.; Albrecht, Beate; Allanson, Judith; Brunner, Han; Bertola, Debora; Chassaing, Nicolas; David, Albert; Devriendt, Koen; Eftekhari, Pirayeh; Drouin-Garraud, Valérie; Faravelli, Francesca; Faivre, Laurence; Giuliano, Fabienne; Guion Almeida, Leina; Juncos, Jorge; Kempers, Marlies; Eker, Hatice Koçak; Lacombe, Didier; Lin, Angela; Mancini, Grazia; Melis, Daniela; Lourenço, Charles Marques; Siu, Victoria Mok; Morin, Gilles; Nezarati, Marjan; Nowaczyk, Malgorzata J M; Ramer, Jeanette C.; Osimani, Sara; Philip, Nicole; Pierpont, Mary Ella; Procaccio, Vincent; Roseli, Zeichi Seide; Rossi, Massimiliano; Rusu, Cristina; Sznajer, Yves; Templin, Ludivine; Uliana, Vera; Klaus, Mirjam; Van Bon, Bregje; Van Ravenswaaij, Conny; Wainer, Bruce; Fry, Andrew E.; Rump, Andreas; Hoischen, Alexander; Drunat, Séverine; Rivière, Jean Baptiste; Dobyns, William B.; Pilz, Daniela T.

In: European Journal of Human Genetics, Vol. 23, No. 3, 01.03.2015, p. 292-301.

Research output: Contribution to journalArticle

Verloes, A, Di Donato, N, Masliah-Planchon, J, Jongmans, M, Abdul-Raman, OA, Albrecht, B, Allanson, J, Brunner, H, Bertola, D, Chassaing, N, David, A, Devriendt, K, Eftekhari, P, Drouin-Garraud, V, Faravelli, F, Faivre, L, Giuliano, F, Guion Almeida, L, Juncos, J, Kempers, M, Eker, HK, Lacombe, D, Lin, A, Mancini, G, Melis, D, Lourenço, CM, Siu, VM, Morin, G, Nezarati, M, Nowaczyk, MJM, Ramer, JC, Osimani, S, Philip, N, Pierpont, ME, Procaccio, V, Roseli, ZS, Rossi, M, Rusu, C, Sznajer, Y, Templin, L, Uliana, V, Klaus, M, Van Bon, B, Van Ravenswaaij, C, Wainer, B, Fry, AE, Rump, A, Hoischen, A, Drunat, S, Rivière, JB, Dobyns, WB & Pilz, DT 2015, 'Baraitser-Winter cerebrofrontofacial syndrome: Delineation of the spectrum in 42 cases', European Journal of Human Genetics, vol. 23, no. 3, pp. 292-301. https://doi.org/10.1038/ejhg.2014.95
Verloes A, Di Donato N, Masliah-Planchon J, Jongmans M, Abdul-Raman OA, Albrecht B et al. Baraitser-Winter cerebrofrontofacial syndrome: Delineation of the spectrum in 42 cases. European Journal of Human Genetics. 2015 Mar 1;23(3):292-301. https://doi.org/10.1038/ejhg.2014.95
Verloes, Alain ; Di Donato, Nataliya ; Masliah-Planchon, Julien ; Jongmans, Marjolijn ; Abdul-Raman, Omar A. ; Albrecht, Beate ; Allanson, Judith ; Brunner, Han ; Bertola, Debora ; Chassaing, Nicolas ; David, Albert ; Devriendt, Koen ; Eftekhari, Pirayeh ; Drouin-Garraud, Valérie ; Faravelli, Francesca ; Faivre, Laurence ; Giuliano, Fabienne ; Guion Almeida, Leina ; Juncos, Jorge ; Kempers, Marlies ; Eker, Hatice Koçak ; Lacombe, Didier ; Lin, Angela ; Mancini, Grazia ; Melis, Daniela ; Lourenço, Charles Marques ; Siu, Victoria Mok ; Morin, Gilles ; Nezarati, Marjan ; Nowaczyk, Malgorzata J M ; Ramer, Jeanette C. ; Osimani, Sara ; Philip, Nicole ; Pierpont, Mary Ella ; Procaccio, Vincent ; Roseli, Zeichi Seide ; Rossi, Massimiliano ; Rusu, Cristina ; Sznajer, Yves ; Templin, Ludivine ; Uliana, Vera ; Klaus, Mirjam ; Van Bon, Bregje ; Van Ravenswaaij, Conny ; Wainer, Bruce ; Fry, Andrew E. ; Rump, Andreas ; Hoischen, Alexander ; Drunat, Séverine ; Rivière, Jean Baptiste ; Dobyns, William B. ; Pilz, Daniela T. / Baraitser-Winter cerebrofrontofacial syndrome : Delineation of the spectrum in 42 cases. In: European Journal of Human Genetics. 2015 ; Vol. 23, No. 3. pp. 292-301.
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abstract = "Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60{\%} of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity.",
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AU - Verloes, Alain

AU - Di Donato, Nataliya

AU - Masliah-Planchon, Julien

AU - Jongmans, Marjolijn

AU - Abdul-Raman, Omar A.

AU - Albrecht, Beate

AU - Allanson, Judith

AU - Brunner, Han

AU - Bertola, Debora

AU - Chassaing, Nicolas

AU - David, Albert

AU - Devriendt, Koen

AU - Eftekhari, Pirayeh

AU - Drouin-Garraud, Valérie

AU - Faravelli, Francesca

AU - Faivre, Laurence

AU - Giuliano, Fabienne

AU - Guion Almeida, Leina

AU - Juncos, Jorge

AU - Kempers, Marlies

AU - Eker, Hatice Koçak

AU - Lacombe, Didier

AU - Lin, Angela

AU - Mancini, Grazia

AU - Melis, Daniela

AU - Lourenço, Charles Marques

AU - Siu, Victoria Mok

AU - Morin, Gilles

AU - Nezarati, Marjan

AU - Nowaczyk, Malgorzata J M

AU - Ramer, Jeanette C.

AU - Osimani, Sara

AU - Philip, Nicole

AU - Pierpont, Mary Ella

AU - Procaccio, Vincent

AU - Roseli, Zeichi Seide

AU - Rossi, Massimiliano

AU - Rusu, Cristina

AU - Sznajer, Yves

AU - Templin, Ludivine

AU - Uliana, Vera

AU - Klaus, Mirjam

AU - Van Bon, Bregje

AU - Van Ravenswaaij, Conny

AU - Wainer, Bruce

AU - Fry, Andrew E.

AU - Rump, Andreas

AU - Hoischen, Alexander

AU - Drunat, Séverine

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AU - Dobyns, William B.

AU - Pilz, Daniela T.

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