Background: Recently, mutations in the highly conserved transactivation domain of MAFB gene have been identified as a cause of multicentric carpo-tarsal osteolysis (MCTO), rare skeletal disorder characterised by extensive bone resorption predominantly of the carpal and tarsal bones and frequently accompanied by progressive renal impairment. The MAFB is a basic leucine zipper transcription factor that is involved in the regulation of osteoclastogenesis and renal development. Clinical presentation of MAFB mutations carriers is very heterogeneous.
Objective and hypotheses: To describe genetic background and growth characteristics in a child with clinical suspicion of MCTO.
Method: Direct sequencing of the MAFB gene.
Results: The 6-year-old girl presented with progressive restricted mobility, pain and edema of wrists. Radiographs revealed osteolysis of proximal phalangs of thumbs, cuneiform and scafoid bones on both ankles. The carpal bones had atypical configuration. Markers of inflammation and juvenile idiopathic arthritis associated antibodies were negative. These findings together with significant proteinuria led us to suspicion of MCTO that has been proven by detection of a heterozygous de novo p.Thr58Ile (c.173C>T) substitution in the MAFB gene. The observed mutation was novel, but located within the mutation hotspot region and predicted to be damaging. In spite of chronic disease and prepubertal status, the patient has accelerated bone age (TW3-RUS 8 years) and dentition. Growth has been accelerated since age of 2 years, in the last 2 years growth velocity has been 8 cm/year (+2.5 S.D.). Actual body height is 124.4 cm (+1 S.D.). She has disproportionally longer extremities, macrocephaly 54.2 cm (+2 S.D.) and orofacial stigmatisation (strabisms, retrognatism, short mandibula and gothic palate).
Conclusion: We present a case of a girl with MCTO caused by novel mutation in the MAFB gene. For the first time, we report accelerated growth and bone age in MCTO patient.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology