Endocrine Abstracts

Introduction: 3M syndrome is a rare autosomal recessive condition that causes short stature, unusual facial features and skeletal abnormalities with normal intelligence. Mutations in CUL7, OBSL1 and CCDC8 genes have been identified as pathogenic. GH treatment outcomes for 3M syndrome appear controversial. Use of human recombinant GH for the treatment of short stature has been trialled in previous studies with some suggesting dysregulation in GH/IGF1 axis while others report no effect of GH treatment in 3M syndrome.

Aim: We report on 4 years of serial growth data in two siblings with a genetic diagnosis of 3M syndrome, which show a good response to GH therapy. Case 1: Term male infant with birth weight 2.3 kg and length of 39 cm (− 5 SDS). At age 5, a genetic diagnosis of CUL7 gene mutation was made with characteristic phenotypic features such as triangular face, squared-off chin, down-slanting palpebral fissures, hypertelorism, long eyelashes, a small fleshy nose with anteverted nares and a long philtrum. He had short 5th fingers with a single flexion crease. He had short 5th toes with clinodactyly and prominent heels. There was flattening of his thoracic spine. He commenced GH therapy at age 7.3 year at height SDS −3.8; he is currently age 11.3 year with a height velocity of 6.7 cm/yr with a height SDS −2.6. Case 2: Term male infant with birth weight 2.5 kg and length of 41 cm (−4 SDS) with similar facial features to his sibling. GH therapy was commenced at age 6yr with an initial height SDS −3.8. He is currently age 10.3 year with a height velocity of 6.5 cm/year and a height SDS −2.8. Both siblings tested negative for GHD. Both remain clinically prepubertal. The DNA samples from parents confirm that they are both carriers of 3M syndrome. Both siblings are compound heterozygotes for the two pathogenic CUL7 gene mutations.

Conclusion: In contrast to published evidence of doubtful efficacy of GH, this case series illustrates successful height SDS increase over a 4 year follow-up. Clinicians should be aware of significant individual variation in relation to GH response in 3M syndrome.