ESPE Abstracts

Background: Distal chromosome 16 duplication syndrome, also known as 16q partial trisomy, is a very rare genetic disorder. Smaller chromosomal copy number variants (CNVs) within the 16q region create partial trisomies, which occur less frequently than full trisomy 16q. Trisomy 16q is generally associated with a multisystemic phenotype including intrauterine growth restriction (IUGR), brain and cardiac defects, intellectual disability and an increased risk of both prenatal and postnatal lethality.

Case Presentation: Here we present the clinical case of a 12-years-old Caucasian boy who referred to Pediatric Endocrinology Outpatient Clinic because of early-onset severe obesity associated with high stature, intellectual disability and facial dysmorphisms. The familial history was negative and his twin brother was healthy. On physical examination he presented cleft palate (surgically corrected at the age of 6 years) and minor dysmorphic facial traits including sparse eyebrows, epicanthus, hypertelorism, midface hypoplasia and thin lips. Height (+1.39 SDS) was above the mean for age and target height, associated with accelerated height growth rate; weight was significantly above the mean for age and BMI SDS was +3.2. Moreover, bone age was found to be about 13 years, in accordance with the chronological age, but testicular volume was still prepubertal in size according to Tanner stage. Biochemical and hormonal evaluation documented high values of LDL-cholesterol and fasting hyperinsulinemia. Audiological tests, echography of the abdomen and heart, brain MRI ruled out major abnormalities or functional disorders. Karyotype and molecular analysis for Kabuki syndrome resulted normal. The genetic analysis has been extended to chromosomal microarray analysis (CMA), that revealed a de novo heterozygous duplication of 16q22.3q24.1 of 10.5 Mb and a heterozygous deletion of 5q14.3, paternally inherited. During follow-up, at the age of 14, the boy seemed to present spontaneous onset of puberty (bone age 14.6 years), persistently severe obesity, slowing of height growth rate with stature still above target height.

Conclusions: Our patient presents a rare genetic abnormality involving chromosome 16 associated with an auxological picture characterized by overgrowth in height and weight, significantly different from the very few cases (18 cases) reported in the scientific literature characterized by stunted growth in height and weight in patients with 16q partial trisomy. This case highlights the great heterogeneity in clinical manifestations and provides new evidence for better defining the phenotypic picture for smaller 16q CNVs.