ESPE Abstracts

Introduction: The genomic disorders caused by rearrangements in region 5q35, including the NSD1 (nuclear receptor SET domain containing protein-1) gene have various phenotypes depending on presence of deletions, duplications or inversions. Patients carrying microduplication have microcephaly, short stature, and mild to moderate intellectual delay or learning disability.

Patients and methods: A six-year-old boy was born small for gestational age (SGA) with birth weight (BW) (-1.1 SDS) and birth length (BL) (-2.83 SDS), in the 31st gestational week (GW). He had microcephaly (- 3.4 SDS), short palpebral fissures, strabismus, myopia, a long nose with long nasal tip and a thin upper lip. He had speech, motor, and intellectual delay with learning disabilities. His younger brother (4.5-year-old) was also born preterm in 32nd GW with normal birth parameters. His development was normal. Both boys had short stature (-3.5 SDS) and (-3.0 SDS). Clinical examination, imaging studies, hormonal and molecular analyses were performed.

Results: The older brother had hypothyroidism (TSH=11.9 uIU/ml and T4=1.13 ng/ml) with Hashimoto thyroiditis (anti TPO antibodies >1000 IU/ml). After few weeks of levothyroxine replacement therapy, he became euthyroid. His IGF1 and IGFBP3 values and growth hormone (GH) concentrations in 2 stimulated tests were within reference range. The performed electroencephalogram (EEG) and brain MRI were uneventful. The younger boy had normal thyroid hormone concentrations, while his IGF1 (48.1 ng/ml) and IGF BP3 (2.01 μg/ml) serum concentrations were low, as well as two tests of pituitary reserve (Peak 4.05 ng/ml). MRI of hypophysis was uneventful. The multiplex ligation probe amplification analysis detected duplication in 5q35.2q35.3 region containing the NSD1 gene, with minimal length of two Mb in both brothers, inherited from their mother. The growth hormone treatment started and increased significantly the growth velocity.

Conclusions: Herein we present a boy with a rare genetic disease associated with growth hormone deficiency. His brother with the same genetic variant has hypothyroidism and Hashimoto thyroiditis. Molecular analysis confirmed maternal origin of duplication in the critical region containing the NSD1 gene.

Key words: microduplication, hypothyroidism, Hashimoto thyroiditis, growth hormone deficiency.