17p13.1 Microduplication Syndrome in a Child, Familial Short Stature, and Growth Hormone Deficiency: A Case Report and Review of the Literature

Abstract

To date, 6 cases of 17p13.1 microduplications have been described in the literature. Intellectual disability is the core feature, together with minor facial dysmorphisms and obesity. We describe the first case of a young patient with a maternally inherited microduplication in 17p13.1 presenting with growth hormone deficiency. The boy was addressed to the endocrine division for growth retardation (weight and height <3rd percentile). Besides minor facial dysmorphisms, physical and neurological examinations were normal except for motor dyspraxia. Basic blood tests and endocrinological investigations were normal, but IGF1 levels were low for his age. Growth hormone deficiency was confirmed. Hypothalamic pituitary MRI was normal. His karyotype was 46XY. Array-CGH analysis detected a 422-kb copy number gain in the spanning region 17p13.1 inherited from his mother. Although familial short stature is considered a “normal” variation of growth retardation, hormonal and genetic investigation is essential in the etiological diagnosis.

Impact of Pituitary Autoimmunity and Genetic Disorders on Growth Hormone Deficiency in Children and Adults

“…The authors concluded that the mutation analysis could clarify the pathophysiological aspects of this syndrome and improve the diagnosis of HIGM patients, addressing the most appropriate therapy to the affected patients [57]. The region p13 of the chromosome 17 is a region of genomic instability that is linked to different rare neuro-developmental genetic diseases, depending on whether a deletion or duplication of the region has occurred [58,59]. The 17p13.1 syndrome is a rare genetic disorder characterized by short stature and GHD associated with intellectual disability, facial dysmorphisms and obesity.…”

“…Recently, Leka-Emiri and coworkers described a case of a child with a maternally inherited 17p31.1 microdeletion presenting with apparently familial short stature but with low IGF1 for their age and impaired GH response to appropriate stimuli. They concluded affirming that, although familial short stature is considered a normal variation of growth retardation, hormonal and genetic investigation is essential in the etiological diagnosis, allowing for an appropriate GH replacement therapy in those with GHD [59]. A heterozygous deletion at chromosome 17p11.2 region that includes RAI1 (or a heterozygous intragenic RAI1 pathogenic variant) characterizes the Smith-Magenis syndrome [60].…”

“…Hearing loss and skeletal, ophthalmologic, cardiac and renal anomalies are usually present, whereas, among the endocrine alterations, hypothyroidism and GHD frequently occur, causing more severe mental and somatic impairment if not corrected early with appropriate replacement therapy [60]. Instead, microdeletions and microduplications concerning the 17p13.3 region can result in either isolated lissencephaly sequence (ILS) or Miller-Dieker syndrome (MDS) [58,59]. Both conditions are associated with a smooth cerebral cortex, or lissencephaly, which leads to developmental delay, intellectual disability and seizures.…”