Clinical Variability in a Noonan Syndrome Family with a Homozygous PTPN11 Gene Variant in Two Individuals
Makaleler > Tam Makale · 2023
Yazarlar: Ruken Yıldırım, Edip Ünal, Şervan Özalkak, Akçahan Akalın, Ayça AYKUT, Nevzat Yılmaz
Journal of Clinical Research in Pediatric Endocrinology, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2023, cilt 16, ss 76-83
DOI: 10.4274/jcrpe.galenos.2023.2023-5-16
Özet
Objective: Noonan syndrome (NS) is characterized by dysmorphic facial features, short stature, congenital heart defects, and varying levels of developmental delays.It is a genetic, multisystem disorder with autosomal dominant inheritance and is the most common of the RASopathies.In approximately 50% of patients, NS is caused by variants in the Protein Tyrosine Phosphatase Non-Receptor Type 11 (PTPN11).This study aimed to evaluate two patients with the previously reported PTPN11 variant in a homozygous state for the first time and seven other family members carrying the same heterozygous variant in terms of clinical, biochemical, genetic, and response to treatment.Materials and Methods: Nine patients diagnosed with Noonan Syndrome (NS) due to the same variants in the PTPN11 gene were included in the study.Results: The age at diagnosis of the patients was found to be 11.5 (range: 6.8-13.9)years and the mean follow-up duration was calculated as 4.7 (range: 1-7.6) years.In eight patients (88.9%), short stature was present.The height SDS of the patients on admission was found to be -3.24± 1.15.In six of the patients, growth hormone treatment was initiated.Cardiovascular or bleeding disorders were not detected in any of the patients.Three (33.3%) of the patients had hearing loss, two (22.2%) had ocular findings and one (11.1%)had a horseshoe kidney.The psychomotor development performance score of the patients was found to be 84.03±17.09and the verbal score was found to be 82.88±9.42.As a result of genetic analysis, a variant in the PTPN11 gene [c.772G>A;(p.Glu258Lys)] that had been previously described in the literature was detected in all patients.Two patients were homozygous for this variant and short stature was more severe in these patients.Conclusion: A variant that had been described before in the literature was detected in the PTPN11 gene and this variant was homozygous in two patients.To the best of our knowledge, these are the first homozygous PTPN11 case reports in the literature, coming from two related consanguineous families.