ESPE Abstracts

Background: Cornelia de Lange (CdLS) syndrome (OMIM #122470) is a complex disease, characterized by distinctive facial features, failure to thrive, microcephaly, intrauterine growth retardation and anomalies in multiple organ systems. The complexity and severity of the endocrine commitment is variable. NIPBL, SMC1A, SMC3, RAD21 and HDAC8 genes, all involved in the cohesin pathway, have been identified to cause CdLS. There are few published studies on the endocrine evaluation in these patients; so our study is aimed at expanding our knowledge in this broad field of research.

Methods: A descriptive study of 29 Spanish patients diagnosed with CdLS was performed. We have analyzed the different metabolic, anthropometric variables. A complete study was carried out, genetic testing and analyzing different endocrine axes including thyroid, adrenal, growth, gonadal, lipid, phosphocalcic and metabolical study.

Findings: 65% of the sample are women and under eighteen years. 44.8% of patients have a history of intrauterine growth restriction (IUGR) in pregnancy, 50 % small for age gestational (SGA) at birth. The mean size of the sample is -3,33 ± 1,94 SD, far from the target size, with a difference of -2,82 ± 2,33 SD. 78 percent of the sample shows height measurements and 71% head circumference below -2 S.D.S. 3 patients have been treated with growth hormone with an an increase in growth rate.

Approximately 50% of our patients harbor genetic variants in the NIPBL gene; however, in 30% of CdLS patients, no molecular alterations have been identified.

No thyroid and adrenal disorders have been observed. Twenty percent of the sample have decreased levels of growth factors, associated with younger patients and nutritional deficit. Impaired glucose tolerance (IGT) was found in 4 of the patients, 30% had increased LDL cholesterol levels. In turn, 27% of the sample shows insulin resistance. Regarding phosphocalcic metabolism, it is worth noting that 75% of patients show decreased levels of 25-0h-vitamin D and 60% of phosphores values below normal. 80% of the sample have decreased levels of testosterone. No other signification alterations have been found.

Interpretation: Our patients have growth retardation, most of them with prenatal onset, according to the clinical criteria of CdLS. Only few reports have commented on endocrine abnormalities in CdLS. In our sample of 29 CdLS patients serious alterations are not observed; however, it is important to carry out an endocrine evaluation, for each individual patient, in order to understand and be able to assess their metabolism adequately.