Siblings with vitamin D-dependent rickets type 1A: Importance of genetic testing and a review of genotype-phenotype correlations.

Vitamin D-dependent rickets type 1A (VDDR1A) is a rare condition caused by biallelic pathogenic variants in CYP27B1, which encodes 25-hydroxyvitamin D3-1-α-hydroxylase. Inadequate activity of this enzyme results in deficient 1α-hydroxylation of inactive 25-hydroxyvitamin D to biologically active 1,25-dihydroxyvitamin D, with consequent adverse effects on calcium and phosphate metabolism. A female child was clinically diagnosed at 18 months old with hypophosphatemic rickets based on phenotype and biochemical testing, with neither parent affected. A subsequent affected male sibling led to the reconsideration of the diagnosis. Exome sequencing showed a homozygous CYP27B1 c.1040T>A (p.Ile347Asn) variant for both children. No variants were found in genes associated with hypophosphatemic rickets. A review of published cases of VDDR1A with homozygous CYP27B1 variants indicates variable clinical presentation, lack of genotype-phenotype correlation, and low serum phosphate at diagnosis in most cases. These findings emphasize the clinical importance of molecular testing as part of the diagnostic evaluation for cases of non-nutritional rickets.

Expanded prenatal phenotype of ALG12-associated congenital disorder of glycosylation including bilateral multicystic kidneys.

Congenital disorders of glycosylation (CDG) are a group of rare autosomal recessive genetic disorders caused by pathogenic variants in genes coding for N-glycosylated glycoproteins, which play a role in folding, degrading, and transport of glycoproteins in their pathway. ALG12-CDG specifically is caused by biallelic pathogenic variants in ALG12. Currently reported features of ALG12-CDG include: developmental delay, hypotonia, failure to thrive and/or short stature, brain anomalies, recurrent infections, hypogammaglobulinemia, coagulation abnormalities, and genitourinary abnormalities. In addition, skeletal abnormalities resembling a skeletal dysplasia including shortened long bones and talipes equinovarus have been seen in more severe neonatal presentation of this disorder. We report on a case expanding the phenotype of ALG12-CDG to include bilateral, multicystic kidneys in a neonatal demise identified with homozygous pathogenic variants in the ALG12 gene at c.1001del (p.N334Tfs*15) through clinical trio exome sequencing.

Understanding Barriers to Human Papillomavirus Vaccination among Parents of 9-10-Year-Old Adolescents: A Qualitative Analysis.

HPV vaccination rates remain low among US adolescents, with only 54% completing the series in 2019. The vaccine is recommended at age 11-12 but can be given as early as age 9. Although it has been found that offering the vaccine earlier improves completion rates by age 13, parents remain reluctant to allow their younger children to initiate this vaccine. The purpose of this study was to better understand parental beliefs regarding receipt of the HPV vaccine among their children at ages 9-10. A 40 min phone interview was completed with 21 participants who were asked about their vaccine viewpoints. Even after receiving one-on-one education from a patient navigator, many caretakers expressed inadequate knowledge of the HPV vaccine and limited exposure to both positive and negative influences. The biggest concern was vaccine side effects, often resulting from a lack of medical understanding. Most parents were reluctant to vaccinate their children at a school-based clinic or pharmacy and believed that the government should not mandate HPV vaccination for public school attendance. Our study provides insight into parental beliefs and attitudes about HPV vaccination at age 9-10 years and barriers that need to be addressed.