Iris coloboma, ptosis, hypertelorism, and mental retardation: Baraitser-Winter syndrome or Noonan syndrome?

Centre for Human Genetics, Liège University, CHU Sart Tilman, Belgium.
Journal of Medical Genetics (Impact Factor: 5.64). 06/1993; 30(5):425-6. DOI: 10.1136/jmg.30.5.425
Source: PubMed

ABSTRACT Three children have been reported with a combination of iris coloboma, ptosis, hypertelorism, and growth and mental retardation with possible autosomal recessive inheritance. We report a single case whose clinical features encompass this syndrome and Noonan syndrome, and discuss the possible interpretations of this complex phenotype.

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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.European Journal of Human Genetics advance online publication, 23 July 2014; doi:10.1038/ejhg.2014.95.
    European journal of human genetics: EJHG 07/2014; · 3.56 Impact Factor
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    ABSTRACT: An Arab child is presented herein with a phenotype that fits the rare Baraitser–Winter syndrome. Her clinical features included a unilateral iris coloboma, ptosis, hypertelorism, epicanthic folds, broad nasal bridge, full cheeks, pointed chin, low set abnormal ears and short neck. In addition, she had cardiac defect, previously undescribed brain anomaly, seizures, hypotonia and developmental delay. Chromosomal analysis of the peripheral lymphocytes and FISH study revealed a normal 46, XX karyotype. To date, Baraitser–Winter syndrome has only been reported in 19 patients of different ethnic families. The present case adds a new finding to the spectrum of malformations published before.
    Egyptian Journal of Medical Human Genetics 10/2010; 11(2):187-191.
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    ABSTRACT: Lissencephaly is a spectrum of severe brain malformations caused by the failure of migrating neurons to reach optimal positions in the developing cerebral cortex. Several syndromes associated with lissencephaly have been characterized in recent years. Identification of the genetic basis of these disorders has brought fascinating insights into the mechanisms of brain development, as well as benefits to patients through improved molecular diagnosis and genetic counseling. This review explores the clinical presentation, radiological features, histological findings and molecular basis of lissencephaly with the aim of facilitating the selection and interpretation of gene tests in patients with 'smooth brain' phenotypes. © 2014 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part C Seminars in Medical Genetics 05/2014; 166(2). · 3.54 Impact Factor

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