Neurodevelopmental delays and macrocephaly in 17p13.1 microduplication syndrome

Abstract

Microduplication of chromosome 17p13.1 is a rarely reported chromosome abnormality associated with neurodevelopmental delays. We describe two unrelated patients with overlapping microduplications of chromosome 17p13.1. The first patient is a 2-year-old male who presented with neurodevelopmental delays and macrocephaly. He was found to have a de novo 788 kb copy gain of 17p13.2p13.1 and a de novo 134 kb copy gain of 17p13.1. These duplications include multiple candidate genes, including EFNB3, NLGN2, DLG4, GABARAP, and DULLARD, which may be responsible for neurodevelopmental delays in affected individuals. The second patient is a 29-year-old female with mild intellectual disability and relative macrocephaly. She was found to have a 62.5 kb copy gain of chromosome 17p13.1 that includes the DLG4, GABARAP, and DULLARD genes. The DLG4, GABARAP, and DULLARD genes included in the microduplications of both our patients appear to be candidate genes for neurodevelopmental delays and macrocephaly in individuals with 17p13.1 microduplication syndrome.

Endocrinological Abnormalities Are a Main Feature of 17p13.1 Microduplication Syndrome: A New Case and Literature Review

“…Her dysmorphic features included a high anterior hairline, broad nasal tip, full lips, mild micrognathia, and prominent antihelix with unfurled helix. A 62.5-kb duplication (7,034,097,308) in chromosome 17p13.1 of unknown origin was detected [Mooneyham et al, 2014].…”

“…Five 17p13.1 microduplication cases have recently been described in the literature and were characterized by intellectual disability and other variable clinical signs [Belligni et al, 2012;Coutton et al, 2012;Kuroda et al, 2014;Mooneyham et al, 2014]. The first reported case was a 15-year-old boy with moderate intellectual disability, non-febrile seizures, hypothyroidism, type 2 diabetes mellitus, hypertriglyceridemia, and astigmatism.…”

“…The last 2 patients were reported by Mooneyham et al [2014]. They described a 2-year-old boy with neurodevelopmental delay, macrocephaly, hypotonia, nystagmus and hyperopia.…”

“…To date, few cases of 17p13.1 microduplication have been reported [Belligni et al, 2012;Coutton et al, 2012;Kuroda et al, 2014;Mooneyham et al, 2014], but a distinct phenotype has not yet been defined. Intellectual disability was observed in all patients as the hallmark feature.…”

“…Indeed, it has been proposed that alteration of dosage-dependent genes may be involved in the genesis of neurodevelopmental disorders in patients with overlapped microdeletions and microduplications of 17p13.1 [Belligni et al, 2012;Coutton et al, 2012;Mooneyham et al, 2014]. Comparing the genetic profiles of cases of 17p13.1 microduplications published up to 2014, Mooneyham et al [2014] identified a common region of overlap including the DLG4 , GABARAP , and CTDNEP1 genes as the candidate genes for intellectual disability in these patients.…”