Hydrops fetalis in a preterm newborn heterozygous for the c.4A>G SHOC2 mutation

Abstract

Fetal hydrops is a condition resulting from interstitial fluid accumulation in fetal compartments secondary to increased capillary permeability and characterized by high rates of perinatal mortality and morbidity. Clinical features include skin edema, hydrothorax, pericardial effusion, ascites with or without polyhydramnios, and placental edema. While it may occur as associated feature in multiple disorders, it has been documented to recur in Noonan syndrome, the most common disorder among RASopathies, but also in cardiofaciocutaneous and Costello syndromes. Here, we report on the occurrence of severe hydrops in a newborn heterozygous for the invariant c.4A>G missense change in SHOC2 which underlies Noonan-like syndrome with loose anagen hair, documenting that it represents a clinically relevant complication in this condition, shared by RASopathies.

Phenotypic variability associated with the invariant SHOC2 c.4A>G (p.Ser2Gly) missense mutation

“…Intriguingly, some of these subjects were reported to have features suggestive of Costello syndrome, especially in early infancy. More recently, a number of reports confirmed the distinctive phenotype associated with the c.4A > G mutation, but also provided evidence for a wider clinical variability characterizing this disorder [Komatsuzaki et al, 2010;Digilio et al, 2011;Lee et al, 2011;Capalbo et al, 2012;Hoban et al, 2012;Gripp et al, 2013;Ş imşek-Kiper et al, 2013;Gargano et al, 2014;Zmolikova et al, 2014]. Table I summarizes the main clinical features of the SHOC2 cases reported in literature.…”

Cleft palate and hypopituitarism in a patient with Noonan‐like syndrome with loose anagen hair‐1

“…Individuals with NSLH1 are more likely to have intellectual disability, relative macrocephaly, sparse/loose anagen hair, and growth hormone deficiency (GHD) compared to individuals with Noonan syndrome (NS) caused by mutations in other genes. The clinical features of 84 patients with NSLH1 have been described (Table ) (Bader‐Meunier et al, ; Capalbo, Melis, et al, ; Capalbo, Scala, et al, ; Choi et al, ; Cordeddu et al, ; Ekvall, Hagenäs, Allanson, Annerén, & Bondeson, ; Ferrero et al, ; Garavelli et al, ; Gargano et al, ; Gripp et al, ; Hoban, Roberts, Demmer, Jethva, & Shephard, ; Kane et al, ; Komatsuzaki et al, ; Lo, Wang, Wong, & Lee, ; Mazzanti et al, ; Mazzanti et al, ; Şimşek‐Kiper et al, ; Tafazoli, Eshraghi, Koleti, & Abbaszadegan, ; Takenouchi et al, ; Tartaglia, Zampino, & Gelb, ; Tosti et al, ; Tosti et al, ; Tosti & Piraccini, ; Zmolikova et al, ). With the possible exception of one patient with unusual but not well‐defined palatal anatomy (Kumar, Chandar, Koduri, & Sankireddy, ), posterior cleft palate (CP) has not been reported in individuals with NS or with NSLH (Cao, Alrejaye, Klein, Goodwin, & Oberoi, ; Mallineni, Yung Yiu, & King, ).…”

Noonan syndrome‐like disorder with loose anagen hair: A second case with neuroblastoma

“…Similarly to what is observed in CS, caused by a narrow spectrum of missense HRAS mutations [Aoki et al, ; Estepp et al, ; Gripp et al, ; Zampino et al, ], such phenotypic homogeneity reflects the genetic homogeneity of this disorder, with all cases being associated with the c.4A>G change [Cordeddu et al, ; Komatsuzaki et al, ; Gripp et al, ]. So far, less than 50 SHOC2 mutation‐positive patients have been reported [Cordeddu et al, ; Komatsuzaki et al, ; Baldassarre et al, ; Gargano et al, ; Takenouchi et al, ; Zmolikova et al, ], with malignancies documented in two [Ekvall et al, ; Gripp et al, ]. Gripp et al [] described a two‐year‐old child with myelofibrosis, a myeloproliferative disorder rarely occurring in children [Tefferi and Vardiman, ].…”