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

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