ESPE Abstracts

Background: To date, six cases of 17p13.1 microduplications have been described in the literature. Intellectual disability is the core feature, together with minor facial dysmorphisms and obesity later in life, but a characteristic phenotype for 17p13.1 microduplication has not been delineated.

Objective and hypothesis: We describe a young patient with a 422 Kb microduplication maternally inherited in 17p13.1, affected by mild intellectual disability and GH deficiency. To our knowledge this is the first case reported presenting GH deficiency.

Patient and methods: A toddler boy was examined at the age of 3.5 years for growth retardation (Weight: 12.8 kg, 3rd percentile, Height: 89.1 cm, <3rd percentile). He is the only child of healthy unrelated parents of Caucasian ancestry. His mother is short (Height: 148.5 cm, <3rd percentile) and was diagnosed with intellectual disabilities in her school age. His father is also short (Height: 154.5 cm, <3rd percentile) but no other family history of intellectual disability or endocrine disorder was reported. He was born at 40 weeks’ gestation after an uneventful pregnancy (weight: 3070 g, 25th percentile, length: 47 cm, 3rd percentile and head circumference: 34 cm, 25th percentile). During infancy and early childhood, the boy presented mild psychomotor developmental delay. At 7 years he was underweight (18 kg, <3rd percentile) but his height was more severely compromised (120 cm, <<3rd percentile). Besides minor facial dysmorphism, he had normal physical examination. He was prepubertal and no asymmetry was appreciated. Neurological examination was normal except for motor dyspraxia.

Results: EEG recordings showed slow background activity without paroxysmal features. Basic blood tests were normal and endocrine investigation revealed normal thyroid and cortisol levels but IGF1 levels were low for his age. GH response to two different stimulation tests was below 10 ng/ml, consistent with GH deficiency. Hypothalamic pituitary MRI was normal. A chromosome analysis revealed a normal male karyotype 46 XY. Array-CGH analysis detected a 422 Kb gain of the copy numbers in the spanning region 17p13.1. The breakpoint was mapped between genomic coordinates chr17: 6,902,072–7,324,005 (Genomic coordinates are listed according to genomic build GRCh37/hg19). No additional aberrations were detected. Both parents were found to have normal karyotype but the mother’s array-CGH analysis was identical to her son. Array-CGH analysis in the father was normal.

Conclusion: Although familial short stature is considered a ‘normal’ variation of growth retardation hormonal and genetic investigation is indispensable for the etiological diagnosis.