Figure 2.

Natural History of ANM. (A) Progressive contracture of intercostal muscles causes a characteristic deformity of the developing thorax and sternochondral joints. (B) Newborns with ANM (open circles) are normal weight at birth (3.4 ± 0.1 kg, range 3.2–3.6 kg) but have somatic growth failure by age 9 months (dotted line; gray shaded area represents World Health Organization reference curves for females, 3rd to 97th centiles). (C) Age of death was accurately known for 87 of 105 ANM patients (solid line); median survival was 18 months (range 0.2–66 months). Also shown for comparison are survival data for nine Palestinian children homozygous for a different TNNT1 variant (c.574_577delinsTAGTGCTGT) [data redrawn from Abdulhaq et al. (9)]. The dashed line shows longer absolute median survival of 70 months for this cohort (chi square=25, P < 0.0001). However, if ventilator dependence is taken as a proxy for death, median ‘ventilator-free’ survival for Amish (solid line) and Palestinian (dotted line) children with recessive TNNT1 myopathy were nearly identical. (D) Between 1923 and 2017, age of death (open circles) was unrelated to date of birth for children with ANM (Pearson’s r = 0.022, P = 0.8372), indicating a lack of disease-modifying therapies and the reluctance of Old Order Amish families to utilize invasive, life-sustaining measures for an otherwise fatal disease.