Endocrine Abstracts

Background: 3q29 microduplication syndrome is a very uncommon genetic disorder with fewer than 40 cases reported, although the wide and heterogenous clinical features make this syndrome hard to diagnose. This syndrome is clinically milder than the 3q29 microdeletion syndrome, which contributes to the high rate of underdiagnosed cases that may exist. Patients affected with this syndrome have a complex phenotype, with non-specific clinical features such as autism spectrum disorders, psychiatric comorbidities, intellectual disability, overweight and craniofacial dysmorphisms, among others. Apart from the previously described ones, obesity, muscular hypotonia, speech delay, microcephaly and ventricular defects are often reported.

Objective: We report the clinical case of a 15-year-old male with a 3q29 microduplication syndrome diagnosed while ruling out a Prader-Willi syndrome. We summarize the literature, and compare our patient phenotype with the previously reported cases.

Methods: Genome-wide copy number analysis was carried out using single-nucleotide polymorphism microarray. The study revealed a 3q29 microduplication with a 1.5 Mb length, affecting DLG1 gene.

Results: A 15-year-old male who was sent to the Endocrinology and Nutrition department due to his overweight, in order to discard secondary causes of obesity and offer treatment. The main medical history of the patient included an early diagnosis of autism with low IQ (<70) in cognitive tests, dysfunctional personality with obsessive-compulsive tendencies and a mixed anxious-depressive syndrome. The patient referred an important and progressive weight gain since he was 8 years old with bad dietetic habits. Physical examination was unremarkable. Low-set ears were the unique facial dysmorphism present in the patient. His height was 1.79 m (85th centile), weight was 117.7 kg (99th centile) and BMI was 36.7 kg/m² (99th centile). The genetic study revealed a 3q29 microduplication affecting DLG1 gene, which could potentially explain the patient’s clinical features. Same mutation was found in the mother. 3q29 microduplication phenotype is widely variable. There are very few clinical cases series published in medical literature, but as reported in some reviews obesity is found in 50% of the cases described.

Conclusions: Our patient showed moderate intellectual disability, autism, psychiatric disorders, obesity and chronic constipation as main feautres of this syndrome. The management of patients affected with this syndrome depends on the moment of diagnosis but includes ophthalmological, cardiac and auditory evaluation, with psychiatric/psychological support when needed. Genetic counselling should be made.