Clinical and hematologic findings in Noonan syndrome patients with PTPN11 gene mutations

Abstract

Reports on Noonan syndrome (NS) have documented multiple types of coagulation defects and bleeding diathesis, and a wide range of clinical presentations. Early studies suggested that a large proportion of NS patients have coagulation defects, whereas more recent reports indicate low rates of coagulopathy. The aim of this study was to evaluate phenotypic characteristics, PTPN11 gene mutations, and hematological and coagulation parameters in 30 clinically diagnosed cases of NS. One of the NS patients had a history of easy bruising; however, his hematological and coagulation tests were normal. None of the other patients had clinical coagulation problems. In the NS group, values for platelet count, activity of factors XI, XII, and protein C were significantly lower than the corresponding means for the control group. However, the results of coagulation tests in the NS group were diagnostically inconclusive and only one patient had clinical signs of coagulopathy. Interestingly, two NS patients had low protein C activity. One of these children had an A1517C mutation and transient myelodysplasia. The other patient had a C1528G mutation in exon 13 that has not been reported previously. Neither of these individuals experienced a thrombotic event or any complication during approximately 3 years of follow-up. For all patients clinically diagnosed with NS, a thorough history of coagulation issues should be taken and first-line coagulation testing should be done to evaluate for bleeding diathesis. However, if these assessments reveal nothing abnormal, complications related to coagulation are unlikely and extensive testing is unnecessary.

Severe congenital thrombocytopaenia - first clinical manifestation of Noonan syndrome

“…The literature review on NS2 4 5 8 reveals multiple types of haemostatic abnormalities attributed to low clotting factor concentrations, in which factor XI is the most frequently described culprit, followed by factor XII and factor VIII.…”

“…In addition, periodic clinical and haematologic control should be maintained for several years, especially in patients with somatic mutations in exons 3 and 13 of PTPN11 gene, such as the reported patient 1 2 13 15…”

“…Noonan syndrome (NS) is an autosomal dominant disorder comprising distinct craniofacial features, congenital heart defects, short stature, genital malformations, abnormalities of the lymphatic system, mild mental retardation and bleeding diathesis 1–3. Haematologic abnormalities in NS occur with an estimated frequency of 20–65%, including clotting factor deficiencies, von Willebrand disease, stem cell dysfunction, thrombocytopaenia and both abnormal platelet counts and function 2–8…”

“…Haematologic abnormalities in NS occur with an estimated frequency of 20–65%, including clotting factor deficiencies, von Willebrand disease, stem cell dysfunction, thrombocytopaenia and both abnormal platelet counts and function 2–8…”

Modifier variant of METTL13 suppresses human GAB1–associated profound deafness

“…We reported that noncoding variants of human HGF cause nonsyndromic hearing loss DFNB39 in many human families (20), and a likely pathogenic variant in MET is associated with DFNB97-linked hearing loss (21). Moreover, deficits of SHP2 and SPRY2 result in hearing loss in humans and mice, respectively (22)(23)(24). Therefore, using real-time PCR and lymphoblastoid cell lines generated from the affected and nonpenetrant individuals of family PK-2, we studied the expression of 37 genes related to HGF signaling ( Figure 8) (25,26).…”