MSX1 mutations have been reported in four unrelated families with autosomal dominant tooth agenesis. In one family, some individuals also had cleft lip and/or palate. We have identified a novel MSX1 mutation (559 C --> T, resulting in Gln187Stop) in three individuals of one family.

Considering the discrepancy between the high incidence rate of agenesis and the relatively small number of reported causative mutations in PAX9, MSX1 and AXIN2 genes, the genetic contribution to oligodontia probably is much more heterogeneous than expected so far. Therefore negative results, like the present exclusion data, should be published more often in order to get a better appreciation of the relative contribution of these specific mutations causing oligodontia. In this context the exact number of tested probands also should be mentioned at all cases. Recent evidence of PAX9-MSX1 protein interactions in odontogenesis as well as other genes and developmental factors should receive more attention.

Funding Acknowledgements Type of funding sources: None. Background Ligamentum flavum hypertrophy due to transthyretin amyloid (ATTR) deposition is common in patients with symptomatic spinal stenosis, although prospective data on systematic screening for coinciding ATTR-cardiomyopathy (CM) are lacking. Purpose To evaluate a prospective screening strategy to identify de novo ATTR-CM in all-comers undergoing spinal stenosis surgery. Methods Patients undergoing symptomatic spinal stenosis surgery were prospectively screened for potential increased ATTR-CM risk, based on predefined criteria on electrocardiography, laboratory (hs-troponin, NT-proBNP), echocardiography and peroperative ligamentum flavum histology. ≥1 Positive criteria mandated ATTR-CM exclusion by HMDP-bonescintigraphy. Results In total 82 consecutive patients (mean age 68±9 years, 48% males) underwent prospective cascade screening. In 90% ≥1 positive risk criterium was noted and 4.1% of patients (n=3/74, 67% male) were identified with de novo ATTR-CM. Importantly, 59% (n=48/82) had ATTR deposition on ligamentum flavum biopsy, of which 21% (n=10/48) being <60 years old. ATTR burden on histology increased with age, the sole independent predictor of ATTR presence (HR 1.15, 95%CI 1.07–1.22, p<0.001). High ATTR burden (Westermark grade 4, ≥10% amyloid on ligamentum flavum histology) was noted in 12% (n=10/82). All 3 de novo ATTR-CM patients had high ATTR burden, translating into a prevalence and positive predictive value (PPV) of 30% (n=3/10) and 85% accuracy for ATTR-CM in Westermark grade 4 patients. Other increased risk markers with PPV>5% are hs-troponin, left ventricular wall thickness ≥12mm, global longitudinal strain >-20% and relative apical sparing. Conclusions High ATTR burden on ligamentum flavum histology during spinal stenosis surgery relates to high risk of coincident ATTR-CM.