ESPE Abstracts

Background: Interstitial deletions of the short arm of chromosome 11 are rare chromosomal anomalies, and are considered to be associated with several clinical conditions including WAGR syndrome.

Objective: To report the clinical and molecular findings in the first case of a heterozygous 11p14.1-p15.3 deletion.

Patient: A Japanese female patient was born at 39 weeks of gestation after an uncomplicated pregnancy and delivery. At birth, her length was 42.0 cm (–3.3 SD), weight 3.15 kg (+0.9 SD), and occipital-frontal circumference (OFC) 36 cm (+2.2 SD). She was found to have large cranial fontanelles and sutures. The closure of the cranial fontanelles was delayed. At 3 years of age, the patient was referred to us because of a short stature. Her height was 83.8 cm (–3.5 SD), weight 11.2 kg (–1.8 SD), and OFC 51 cm (+1.8 SD). She had relative macrocephaly and frontal bossing. She did not show either any motor or mental development delay, and had no other dysmorphic features. Endocrinological studies indicated normal growth hormone secretion and thyroid functions.

Genetic analyses: A G-banded chromosome and SNP array analyses showed a 9.2-Mb heterozygous deletion at 11p14.1-p15.3 in the patient. 25 genes, including NELL1, have been associated with this deletion. The clinically normal parents were found to not have the deletion.

Conclusions: The loss of the Nell1 function leads to skeletal defects in the cranial vault and vertebral column, and overexpression of Nell1 causes craniosynostosis in mice. These results imply that short stature and an abnormality of membranous ossification could be explained by haploinsufficiency of NELL1 on 11p14.1-p15.3.