American Journal of Medical Genetics Part A最新文献

Radial ray deficiency (RRD) may be isolated, without other congenital anomalies or co-occurring with other, non-RRD, congenital anomalies. The prevalence and the types of co-occurring anomalies are variable in the reported studies. The aim of this study was to obtain the prevalence and the types of co-occurring congenital anomalies among cases with RRD in a geographically well-characterized population of 387,067 consecutive births in northeastern France from 1979 to 2007 including live births, stillbirths and terminations of pregnancy. During the study period 83 cases with RRD were ascertained (prevalence of 2.14 per 10,000 births), 63 cases (75.9%) had co-occurring anomalies. Cases with co-occurring anomalies were divided into chromosomal anomalies (18 cases, 22%), syndromic conditions (syndromes and associations, 23 cases, 28%), and multiple congenital anomalies (MCA) (22 cases, 26%). Trisomies 18 and autosomal deletions were the most common chromosomal abnormalities. Thrombocytopenia absent radii syndrome, VACTERL association, Fanconi anemia, Roberts syndrome, and Holt-Oram syndrome were the most common syndromic conditions. Anomalies in the musculoskeletal, the cardiovascular, the urinary, and the orofacial system were the most common co-occurring anomalies in cases with MCA. As cases with RRD have often co-occurring congenital anomalies, a multidisciplinary checkup of these cases is recommended.

Various forms of oral involvement have been reported in patients with neurofibromatosis 1 (NF1). Here, we analyze register-based associations between NF1 and hospital visits related to oral infections. The Finnish NF1 cohort encompasses all individuals with verified NF1 who have visited the Finnish central and university hospitals in 1987-2011. The Finnish Care Register for Health Care allowed the follow-up of 1349 individuals with NF1, their 1894 siblings without NF1, and 13,870 matched controls for diagnoses related to oral infections in 1998-2014. We observed clearly increased hazards for hospital visits associated with dental caries (ICD-10 K02; NF1 vs. controls, hazard ratio [HR] 4.42, 95% CI 3.23-6.04), diseases of pulp and periapical tissues (K04; HR 3.85, 95% CI 2.68-5.54), and gingivitis and periodontal diseases (K05; HR 3.63, 95% CI 2.37-5.56). In contrast, hospital visits related to diseases of salivary glands (K11), and stomatitis and related lesions (K12) did not show significantly increased hazard in NF1 compared with the controls or the non-NF1 siblings. In conclusion, the findings suggest that hospital visits related to oral infections are relatively common among individuals with NF1. The results highlight the need for early detection, proactive prevention, and timely treatment of oral infections in individuals with NF1.

Haploinsufficiency of SF3B2 is associated with craniofacial microsomia, characterized by mandibular hypoplasia and microtia, often with preauricular tags or pits, epibulbar dermoids, and cleft palate. In addition, extracraniofacial anomalies may be present, such as skeletal, cardiac renal, and abnormalities of the central nervous system. Variants have been either de novo or inherited, and both inter- and intrafamilial variability has been observed. Here we describe a patient referred for exome sequencing for a complex congenital heart defect and Hirschsprung disease found by exome sequencing to be heterozygous for a loss of function variant, c.945dup (p.Val316SerfsTer5), in SF3B2. This variant was inherited from a parent with an isolated cardiac defect. Interestingly, neither have the defining craniofacial features or other dysmorphisms. This report further illustrates the degree of phenotypic variability seen in SF3B2-related disease and expands the spectrum to include Hirschsprung disease.

Phenylketonuria (PKU) is a genetic metabolic disorder that causes the accumulation of phenylalanine (Phe) in tissues, leading to intellectual disability, seizures, and socioemotional challenges. The role of social determinants of health (SDOH) in PKU management has not been formally studied, and this investigation evaluates the association between in-home and in-office factors on blood Phe levels in PKU patients. We conducted a retrospective chart review on over 200 patients attending the well-resourced PKU Clinic at Lurie Children's Hospital of Chicago. Data included patients' average Phe level, various demographic information, and CDC/ATSDR social vulnerability index (SVI) score. The analysis revealed no significant association between social vulnerability status and average Phe level. However, a significant correlation was found between sapropterin dihydrochloride use and average Phe level. Age interacted separately with sex assigned at birth, pegvaliase use, total Phe samples submitted, and the presence of genetic testing to significantly influence the average Phe level. This study highlights the multifactorial influences on PKU management and underscores the importance of social resources, such as clinic social workers and state-provided formula, in modulating the effects of SDOH on PKU control. Further research in different healthcare settings is needed to understand the social determinants affecting PKU patients comprehensively, which will strengthen advocacy efforts for this population.