Fig. 1: Patients’ clinical features and MTX2 mutations.

a Pictures and electropherograms of patient MADM1. At age 11 years, the girl showed severe growth retardation, mandibular recession, a pinched nose with hypoplastic alae nasi, long philtrum, prominent eyes, dental overcrowding, sparse eyebrows and body hair along with lipodystrophy and atrophic wrinkled skin. The homozygous c.2T>A (p.Met1Lys) MTX2 variant was identified and the heterozygous state of the parents confirmed the mode of inheritance as autosomal recessive. b Pictures and electropherograms of patient MADM2 at age 14 years, showing clinical features very similar to patient MADM1. The homozygous c.544-1G>C MTX2 splicing variant was confirmed by Sanger sequencing. c Pictures and electropherograms of patient MADM3 at age 2 years. He showed mandibular recession, prominent eyes, alopecia, long Stahl’s ears, and lipodystrophy. The homozygous c.208+3_208+6del MTX2 splicing variant was observed and confirmed by Sanger sequencing, and the carrier state of the parents was in accordance with autosomal recessive inheritance pattern. d Pictures of patients and family tree of the MADM4 consanguineous family. The homozygous MTX2 deletion c.603del (p.Tyr202Ilefs*26) was identified in three affected children (MADM4-1, MADM4-2, MADM4-3), all presenting with progeroid facies including high forehead, bulbous nose with depressed nasal bridge, prominent eyes, long philtrum, small mouth, small mandible, and long Stahl’s ears. Informed consent was obtained to publish patient images. See Supplementary Note 1, Supplementary Figs. 1, 2, and Supplementary Data File for additional clinical and radiological features.