Background: 3-M syndrome is an autosomal recessive growth disorder characterised by severe pre- and post-natal growth retardation caused by mutations in CUL7, OBSL1 or CCDC8. Clinical characteristics include dysmorphic facial features and fleshy prominent heels with a variable degree of radiological abnormalities.
Objective and hypotheses: Evaluation of four new patients from two different families. Cases:
Family-1/Patients-1,2: Two brothers (16.6 (patient-1) and 8.5 (patient-2) years-old) were referred for marked short stature. Their anthropometric measurements at birth was not known but they were born small. Their parents were first degree cousin. Physical examination revealed a severe short stature (HeightSDS:6.1/5.8) and dysmorphic features. Pubertal stages were Tanner-2 and Tanner-1. Their motor and mental developments were normal. Endocrine work-up was normal. Genetic testing confirmed a mutation in the CUL7 gene. They had a normal response to GH stimulation test. Adequate rise was noted in insulin-like growth factor-I(IGF-I) and IGF binding protein-3(IGFBP-3) levels with IGF-1 generation test. GH Metin veya web sitesi adresi yazın ya da bir dokümanı çevirin. treatment was started at 11 years-old (Patient-2). Pubertal stage of patient-2 is Tanner I at thirteen years of age.
Family-2/Patients-3,4: Two sisters [Elder one (patient-3) at 0.75 years-old, younger one (patient-4) at 2.5 years old] were referred for marked short stature. They had intrauterine growth retardation. Their parents were third degree-cousin. Physical examination revealed a severe short stature (HeightSDS:-6.0/-5.3) and dysmorphic features. Their motor and mental development were normal. Endocrine work-up was normal. Genetic testing confirmed a mutation in the OBSL1 gene. They had a normal response to GH stimulation and IGF generation test. GH treatment was started at 4.8 years-old (Patient-3)
Conclusion: syndrome should always be considered in the differential diagnosis of short patients with intrauterine growth retardation. Children are often treated by GH but there is no obvious demonstration of its efficiency. 3M syndrome might cause delayed puberty in boys.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology