Follow Your Nose: Repeat Nasal Bone Evaluation in First-Trimester Screening for Down Syndrome.

OBJECTIVE: Examine whether repeat nasal bone evaluation following an absent/uncertain nasal bone on first-trimester screening (FTS) improves Down syndrome (DS) screening specificity. METHODS: A retrospective chart review of FTS sonograms in one center from January 2015 to January 2018 was performed. Data was extracted for those with an absent/uncertain nasal bone. Repeat evaluations were offered. RESULTS: Of 6780 FTS sonograms, 589 (8.7%) had an absent/uncertain nasal bone. Upon repeat exam, 268/376 (71.3%) had a present nasal bone. Compared with Black patients, patients of other ethnicities were more likely to have a present nasal bone on exam 2 (P < .00001). Of 268 patients with a present nasal bone on exam 2, 37 (13.8%) had an abnormal DS risk following exam 1; 34/37 (91.9%) normalized following nasal bone visualization, dropping the screen positive rate to 1.1%. CONCLUSION: Repeat nasal bone examination is beneficial in refining DS risk assessment and improves the specificity of FTS.

Sacral protuberance with cleft lip and palate: Prenatal presentation of 3MC syndrome.

3MC syndromes are rare heterogeneous autosomal recessive conditions previously designated as Mingarelli, Malpuech, Michels, and Carnevale syndromes, characterized by dysmorphic facial features, facial clefts, growth restriction, and intellectual disability. 3MC is secondary to mutations in the MASP1, MASP3, COLEC11, and COLEC10 genes. The number of patients with 3MC syndrome with known mutations in the COLEC11 or MASP1 is, to date, less than 50. At the time this case presented (2015), the only gene identified in Online Mendelian Inheritance in Man to be associated with 3MC syndrome was MASP1. We present, to the best of our knowledge, the first prenatal report of 3MC syndrome, secondary to a homozygous variant in MASP1. Fetal findings included bilateral cleft lip and palate, abnormality of the sacral spine, a right echogenic pelvic kidney, and brachycephaly. 3MC syndrome should be considered as part of the differential diagnosis when fetal ultrasound detects facial clefts and spinal defects, as the risk of recurrence is significant and a molecularly confirmed diagnosis allows for alternate reproductive options.

Literacy assessment of preimplantation genetic patient education materials exceed national reading levels.

PURPOSE: In vitro fertilization with preimplantation genetic testing (IVF+PGT-M) reduces the risk of having a child affected by a heritable condition, yet only one-third of eligible patients are aware of this reproductive option. Access to education materials written at appropriate literacy levels could raise patients' awareness, but there is a mismatch between patient reading ability and the literacy demand of most materials. This study aimed to systematically identify written education materials on IVF+PGT-M and evaluate their literacy levels. We hypothesized that materials would fail to meet standards set by the Joint Commission and Centers for Disease Control and Prevention (CDC). METHODS: To identify patient education materials about IVF+PGT-M from academic databases and public-facing sources, an environmental scan was performed. Materials were analyzed using three validated scales: Simple Measure of Gobbledygook, Patient Education Materials Assessment Tool, and Clear Communication Index. RESULTS: Seventeen patient education materials about IVF+PGT-M were identified from patient education databases, a consumer search engine, and professional organizations. The median reading level was 14.5 grade, median understandability was 74.2%, and median comprehensibility was 73.3%. CONCLUSIONS: For most American adults, materials about IVF+PGT-M are not readable, understandable, or clear. The Joint Commission requires patient education materials be written at or below 5th grade reading level and the CDC recommends a 90% minimum score for comprehensibility. No evaluated material met these guidelines. Patient education materials that exceed average American literacy skills may perpetuate disparities in the utilization of IVF+PGT-M. Materials that communicate this complicated subject at an understandable level are needed.

Not just a carrier: Clinical presentation and management of patients with heterozygous disease-causing alkaline phosphatase (ALPL) variants identified through expanded carrier screening.

Hypophosphatasia (HPP) is an underrecognized, complex bone mineralization disorder with variable manifestations caused by one or two deleterious variants in the alkaline phosphatase (ALPL) gene. Expanded carrier screening (ECS), inclusive of ALPL, intends to inform reproductive risk but may incidentally reveal an HPP diagnosis with 50% familial risks. We sought to investigate at-risk individuals and develop a multidisciplinary referral and evaluation protocol for ECS-identified ALPL heterozygosity. A retrospective database query of ECS results from 8 years to 1 month for heterozygous pathogenic/likely pathogenic ALPL variants was completed. We implemented a clinical protocol for diagnostic testing and imaging, counseling, and interdisciplinary care management for identified patients, and outcomes were documented. Heterozygous ALPL variants were identified in 12/2248 unrelated patients undergoing ECS (0.53%; heterozygote frequency 1/187). Of 10 individuals successfully contacted, all demonstrated symptomatology and/or alkaline phosphatase values consistent with HPP. ECS may reveal incidental health risks, including recognition of missed HPP diagnoses in ALPL heterozygotes. In our cohort, all ECS-identified ALPL heterozygotes with clinical and/or biochemical data available demonstrated features of HPP. Referral to a genetics professional familiar with HPP is indicated for family history assessment, genetic counseling, cascade testing, and long-term bone health management.

Attitudes toward prenatal genetic testing for Treacher Collins syndrome among affected individuals and families.

Treacher Collins syndrome (TCS) is a craniofacial syndrome that is both phenotypically variable and heterogeneous, caused by mutations in the TCOF1, POLR1C, and POLR1D genes. We examined attitudes towards TCS prenatal genetic testing among affected families using a telephone questionnaire. Participants were 31 affected adults and relatives recruited primarily through families cared for in the mid-Atlantic region. Nineteen participants (65%) reported that they would take a TCS prenatal genetic test which could not predict degree of disease severity. Interest in TCS genetic testing was associated with higher income, higher concern about having a child with TCS, lower religiosity, lower concern about genetic testing procedures, and having a sporadic rather than familial mutation. Over half reported that their decision to have TCS genetic testing would be influenced a great deal by their desire to relieve anxiety and attitudes toward abortion. Ten participants (32%) reported that they would be likely to end the pregnancy upon receiving a positive test result; this was lower amongst TCS affected individuals and higher amongst participants with children with TCS. Genetics healthcare providers need to be aware of affected individuals' and families' attitudes and interest in prenatal genetic testing for TCS, and the possible implications for other craniofacial disorders, so that patients' information needs can be met.