Familial incidence and associated symptoms in a population of individuals with nonsyndromic craniosynostosis.

PurposeCraniosynostosis is a common cranial malformation occurring in 1 per 2,000-2,500 births. Isolated defects (nonsyndromic) occur in ~75% of cases and are thought to have multifactorial etiology. It is believed that each suture synostosis is a distinct disease, with varying phenotypes and recurrence rates.MethodsWe analyzed family histories of 660 mutation-negative nonsyndromic craniosynostosis patients and symptoms in 189 of these patients.ResultsThe incidence rate of craniosynostosis was highest for first-degree relatives of probands with metopic craniosynostosis (6.4%), followed by those with complex craniosynostosis (4.9%), sagittal craniosynostosis (3.8%), lambdoid craniosynostosis (3.9%), and coronal craniosynostosis (0.7%). Across all suture types, siblings had a greater craniosynostosis incidence rate than parents (7.5 vs. 2.3%). In phenotype comparisons, patients with complex craniosynostosis had the highest frequency of reported symptoms and those with sagittal craniosynostosis had the lowest. Ear infections, palate abnormalities, and hearing problems were more common in complex craniosynostosis patients. Visual problems were more common in coronal craniosynostosis, and metopic craniosynostosis patients noted increased frequency of chronic cough.ConclusionOur data suggest that the genetic component of nonsyndromic craniosynostosis appears to be suture specific. The incidence rate of craniosynostosis among first-degree relatives varies by suture and family member. Additionally, the phenotype of each suture synostosis shows both unique and shared features

Characterization of a t(5;8)(q31;q21) translocation in a patient with mental retardation and congenital heart disease: implications for involvement of RUNX1T1 in human brain and heart development

The chromosome break points of the t(8;21)(q21.3;q22.12) translocation associated with acute myeloid leukemia disrupt the RUNX1 gene (also known as AML1) and the RUNX1T1 gene (also known as CBFA2T3, MTG8 and ETO) and generate a RUNX1–RUNX1T1 fusion protein. Molecular characterization of the translocation break points in a t(5;8)(q32;q21.3) patient with mild-to-moderate mental retardation and congenital heart disease revealed that one of the break points was within the RUNX1T1 gene. Analysis of RUNX1T1 expression in human embryonic and fetal tissues suggests a role of RUNX1T1 in brain and heart development and support the notion that disruption of the RUNX1T1 gene is associated with the patient's phenotype

A clinical study of 31 individuals with midline facial defects with hypertelorism and a guideline for follow-up Estudo clínico de 31 indivíduos com defeitos de linha média facial com hipertelorismo e diretrizes para seguimento clínico

In order to contribute to clinical delineation of midline facial defects with hypertelorism (MFDH) and to etiologic diagnosis of the isolated form, 31 patients with MFDH unaffected by known syndromic associations were evaluated. Group A included patients personally examined by the authors, while Group B included those previously evaluated by other geneticists. Among the 14 patients from Group A, there were 7 with distinct pictures of multiple congenital anomalies. In Group B, 5 of the 17 patients also exhibited a distinct pattern of defects. Among isolated MFDH, there was association with anomalies of the skull and facial bones (13/14), otorhinologic (11/16), central nervous system (9/16), and ocular (6/7), and audiologic (3/16); 1/3 of the cases had a relevant gestational intercurrences. Isolated FNM may have involvement of environmental components in some cases; the possibility of a syndromic picture should be extensive investigated. Follow-up of such patients must include the examinations herein performed.<br>Objetivando contribuir com o delineamento clínico de defeitos de linha média facial com hipertelorismo (DLMFH) e com o diagnóstico etiológico das formas isoladas, foram avaliados 31 indivíduos com DLMFH sem condições clínicas definidas. O Grupo A constituiu-se de pacientes examinados pessoalmente e o Grupo B, inicialmente, por outro geneticista. Entre os 14 pacientes do Grupo A, detectou-se 7 novos quadros de anomalias múltiplas (AM). No Grupo B, 5 dos 17 pacientes exibiram um quadro clínico único e peculiar. Nos casos de DLMFH isolados, detectou-se associação com anomalias de ossos de crânio e face (13/14), otorrinolaringológicas (11/16), de sistema nervoso central (9/16), oculares (6/7), e audiológicas (3/16); houve antecedentes gestacionais relevantes em 1/3. Existem evidências de envolvimento de fatores ambientais em parte dos casos de formas isoladas de DLMFH, devendo-se atentar para a possibilidade de um quadro distinto de AM. Todas as investigações realizadas são úteis para avaliação e seguimento clínico