ESPE Abstracts

Background: Growth is a complex process influenced by several genetic factors both pre and postnatal, in which 80% of the height variation is explained by genetic factors. Nevertheless, the standard medical evaluation of short stature (SS) relies upon physical examination and laboratory parameters and identifies a pathological cause of SS in 1–40% of individuals. Recent advances in genetic diagnosis are revolutionizing the clinician’s ability to obtain a molecular diagnosis for patients with growth disorders. The Wolf-Hirschhorn syndrome (MIM194190) is a complex genetic disorder caused by loss of genomic material from the short arm of chromosome 4 (4p16.3 region), including LETM1 and WHSC1 genes.

Case presentation: We report a female patient, 1 year old, presented with severe SS (−4.36 z-score), IUGR, neonatal jaundice, syndromic facies (microcephaly, prominent glabella, high arched eyebrow, broad nasal bridge and hypertelorism, short filtrum, mouth turned down, micrognathia, malformed ears), delayed psychomotor development, intra-atrial communication and seizures. She had a female karyotype, without any suggestion of chromosome alteration. We performed the chromosomal microarray analysis (CMA) on the proband and her parents. The array used was Affymetrix’s GeneChip CytoScan HD SNP array. CMA detected four de novo genomic imbalances, corresponding to a 3.86 Mb microdeletion at 4p16.3, a 1.55 Mb microdeletion at 4p16.3, a 320 kbp microduplication at 5p13.2 and a 4.21 Mb microduplication at 9p24.3. The CMA showed that the microdeletion at 4 p was harbouring several genes, including LETM1, WHSC1, WHSC2, MSX1 that have been described and related to the Wolf-Hirschhorn syndrome.

Conclusion: These findings allowed identification of a genomic cause for the clinical features of the proband. Molecular diagnosis is important because it can end the diagnostic workup for the patient, it may alert the clinician to other medical comorbidities for which the patient is at risk, and it is extremely valuable for the genetic counselling.