Di Donato N, Kuechler A, Velgano S, Heinritz W, Bodurtha J, Merchant SR,
Breningstall G, Ladda R, Sell S, Altmüller J, Bögershausen N, Timms AE, Hackmann K, Schrock E, Collins S, Olds C, Rump A, Dobyns WB. Update on the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome. Am J Med Genet A. 2016 May 30. doi: 10.1002/ajmg.a.37771. [Epub ahead of print]
Baraitser-Winter cerebrofrontofacial syndrome is caused by heterozygous missense mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1. Recently, we characterized the large cohort of 41 patients presenting with this condition. Our series contained 34 patients with mutations in ACTB and only nine with ACTG1 mutations. Here, we report on seven unrelated patients with six mutations in ACTG1-four novel and two previously reported. Only one of seven patients was clinically diagnosed with this disorder and underwent ACTB/ACTG1 targeted sequencing, four patients were screened as a part of the large lissencephaly cohort and two were tested with exome sequencing. Retrospectively, facial features were compatible with the diagnosis but significantly milder than previously reported in four patients, and non-specific in one. The pattern of malformations of cortical development was highly similar in four of six patients with available MRI images and encompassed frontal predominant pachygyria merging with the posterior predominant band heterotopia. Two remaining patients showed mild involvement consistent with bilaterally simplified gyration over the frontal lobes. Taken together, we expand the clinical spectrum of the ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome demonstrating the mild end of the facial and brain manifestations.
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 MJ, 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. Baraitser-Winter cerebrofrontofacial syndrome: delineation of the spectrum in 42 cases. Eur J Hum Genet. 2015 Mar;23(3):292-301.
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.
Kemerley A, Sloan C, Pfeifer W, Smith R, Drack A. A novel mutation in ACTG1 causing Baraitser-Winter syndrome with extremely variable expressivity in three generations. Ophthalmic Genet. 2016 Apr 20:1-5.ReplyDelete
Baraitser-Winter syndrome (cerebrofrontofacial syndrome, type 3) is a rare developmental disorder typified by hypertelorism, ptosis, high-arched eyebrows, ocular coloboma, and brain malformations. Other common manifestations include hearing loss, short stature, seizures, intellectual impairment, muscle dysfunction, and abnormalities of the kidney and urinary system. This syndrome is caused by missense mutations in the genes ACTB or ACTG1, both of which encode for cytoplasmic actin proteins crucial for proper development of many organs in the human body. There are no reports of familial transmission; all reported cases have been new mutations. However, different mutations in ACTG1 have been reported to cause isolated non-syndromic hearing loss, with many reported cases of autosomal dominant (AD) inheritance. We have identified a three-generation pedigree segregating a novel mutation in the ACTG1 gene that causes Baraitser-Winter Syndrome with extremely variable expressivity, leading to an initial diagnosis of isolated AD hearing loss in two members. Subtle optic nerve signs not previously reported in this syndrome are also documented in one patient.
Rossi M, Guerrini R, Dobyns WB, Andria G, Winter RM. Characterization of brain malformations in the Baraitser-Winter syndrome and review of the literature. Neuropediatrics. 2003 Dec;34(6):287-92.ReplyDelete
Baraitser-Winter syndrome is a rare autosomal recessive disorder characterized by developmental delay, dysmorphic features, and multiple malformations also involving the brain. We report a further case and provide updated information about an unrelated girl reported in the original paper by Baraitser and Winter. Both of them presented with pachygyria and the latter case was recently found to have subcortical band heterotopia on high resolution brain MRI imaging. These two patients and a review of the previously reported cases indicate that a specific pattern of brain anomalies falling in the agyria-pachygyria-band spectrum is associated with this dysmorphic syndrome, which may be considered another example of syndromic neuronal migration defect.
Shiihara T, Maruyama K, Yamada Y, Nishimura A, Matsumoto N, Kato M, Sakazume S. A case of Baraitser-Winter syndrome with unusual brain MRI findings: pachygyria, subcortical-band heterotopia, and periventricular heterotopia. Brain Dev. 2010 Jun;32(6):502-5.ReplyDelete
Baraitser-Winter syndrome (BaWS) is characterized by iris coloboma, ptosis, hypertelorism, and mental retardation; it is a rare multiple congenital anomaly or a mental-retardation syndrome of unknown etiology. Patients suffering from this syndrome have been also found to show brain anomalies such as pachygyria, subcortical-band heterotopia (SBH), and hippocampal malformations; therefore, these anomalies have been included in the phenotypic spectrum of this syndrome. We report the case of a Japanese boy suffering from BaWS; the patient's brain magnetic resonance imaging scan revealed pachygyria, SBH, and periventricular heterotopia. However, the results of the genome-wide array comparative genomic hybridization did not reveal any chromosomal rearrangements.
Rivière JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet. 2012 Feb 26;44(4):440-4, S1-2.ReplyDelete
Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes.
I’m here to testify about what DR. ISIBOR did for me. I have been suffering from (GENITAL HERPES VIRUS) disease for the past 3 years and had constant pain and inching, especially in my private part. During the first year, I had faith in God that i would be cured someday.This disease started circulating all over my body and I have been taking treatment from my doctor, few weeks ago I came across a testimony of Rose Smith on the internet testifying about a Man called DR. ISIBOR on how he cured her from 7 years HSV 2. And she also gave the email address of this man, advise anybody to contact him for help on any kind of diseases that he would be of help, so I emailed him telling him about my (HSV 2) he told me not to worry that I was going to be cured!! Well, I never doubted him I have faith he can cure me too,, DR. ISIBOR prepared and sent me Healing Oil, Soap, roots and herbs which I took. In the first one week, I started experiencing changes all over me, after four weeks of using his Roots/ Herbs, Oil and Soap, I was totally cured. no more inching , pain on me anymore as DR. ISIBOR assured me. After some time I went to my doctor to do another test behold the result came out negative. So friends my advise is if you have such disease or know anyone who suffers from it or any other disease like HPV, HIV, ALS, CANCER etc. you can contact DR. ISIBOR for help via email} email@example.com or call +2348107855231ReplyDelete