Endocrine Abstracts

JOINT1719

Introduction: Prader-Willi syndrome (PWS) is a multiorgan neurodevelopmental disease, caused by parental genomic imprinting disorder in 15q11-13 region.

Aim: We present an atypical clinical picture and diagnostic difficulties in a 5.5-year-old girl with PWS.

Case report: A girl born from GVI (2xspontanous miscarriages), by caesarean section in 35 Hbd because of IUGR and worsening of the foetal state, with birth weight 1160g (-4.9 SD), length 41cm (-2.6 SD), 8-9 points of Apgar score. She required nCPAP and feeding by a gastric tube from 5th day until 3 months of life. Results of karyotype, routine method, and aCGH were normal. At the age of 1.5 years short stature and low weight, hypotonia, strabismus, dolichocephalic shape of a head, downturned mouth corners, narrowing fingers, slight clinodactyly of the IV and V toes were observed. Silver-Russell syndrome and PWS were considered, multiloci methylation analysis (MLID) was performed, the results showed normal methylation pattern in analysed loci. At the age of 3.5 years there were still significant short stature (-5.5 SD) and low weight (-3.8 SD), head circumference -3.5 SD, BMI -2.5 SD, legs circumference asymmetry R>L. Due to the phenotype suggesting PWS, methylation analysis of 15q11-13 region was performed and showed abnormal SNRPN and MAGEL2 methylation pattern, that allowed to verify the MLID result and diagnose PWS. The microsatellite sequence analysis showed chromosome 15 maternal disomy (mUPD15). Further analysis of 14 loci showed mUPD in 3, 3 alleles present in 1 locus (2 maternal, 1 paternal) and non-informative results in other loci. Additional tests revealed 1.5 year delay of bone age and normal IGF1 level. The rhGH treatment was started 4 months after the diagnosis with the increasing dose from 0.47 to 0.74 IU/kg/wk, with improved growth velocity from 4.8 to 9.6 cm/yr, muscle tone and psychomotor development. After 1.5 year height is at the level -4 SD, weight -2.7 SD, head circumference -3.1 SD, BMI -1.8 SD, appetite has not been increased. Family history revealed the patient’s two older brothers have started rhGH treatment because of GHD. Due to unclear reason of deep pre- and postnatal short stature NGS examination was performed with no pathogenic/potentially pathogenic variants identified. A comparative WES study in siblings is considered.

Conclusions: Aimed molecular diagnostic tests and sometimes repeating/widening diagnostics in unclear clinical settings are needed. The results of the studies to date do not explain the cause of such significant growth retardation in our patient.