Rapid Weight Loss and Severe Failure to Thrive Mimicking Lipodystrophy Syndrome in a 1-Year-Old Taiwanese Girl with Costello Syndrome

Abstract

Costello syndrome (CS) is a type of RASopathy caused mainly by de-novo heterozygous pathogenic variants in the HRAS gene located on chromosome 11p15.5. The phenotype of CS is characterized by prenatal overgrowth, postnatal failure to thrive, curly or sparse fine hair, coarse facial features, and multisystem involvement, including cardiovascular, endocrine, and gastroenterological disorders. We present a one-year-old girl with rapid weight loss and severe failure to thrive. She had gastroesophageal reflux at the age of four months with subsequent rapid weight loss. The loss of fat tissue over the whole body, refractory to a hypercaloric diet, mimicked the presentation of progressive lipodystrophy and masked the dysmorphic features of CS. The final diagnosis of CS was made by whole exome sequencing, which demonstrated a hot-spot, heterozygouspathogenic variant in the HRAS gene (c.34G > A, rs104894229). Our patient illustrates that the excessive energy needs in CS patients may lead to severe failure to thrive and cause challenges in diagnosing CS. This case also highlights the importance of recognizing CS in patients with a history of prenatal overgrowth, polyhydramnios presenting with severe failure to thrive refractory to pharmacotherapy and tube feeding.

Management of nutritional and gastrointestinal issues in RASopathies: A narrative review

“…The first phase is the most challenging one as almost all patients show swallowing and feeding difficulties. Specifically, a pathological increase of amniotic fluid volume is constantly detected, probably reflecting the early prenatal onset of swallowing disorders frequently experienced during the postnatal period (Bertola et al, 2017; Digilio et al, 2008; Digilio et al, 2011; Gripp et al, 2012; Perniola et al, 2007; Pratesi, Santos, & Ferrari, 1998; Syu et al, 2022; Weaver et al, 2022). Hennekam (2003) confirmed the high prevalence of polyhydramnios, found in 58% (39/67) of mothers of individuals with CS, a high prevalence of poor feeding (97%, 56/58) and hypotonia among infants.…”

“…Hennekam (2003) confirmed the high prevalence of polyhydramnios, found in 58% (39/67) of mothers of individuals with CS, a high prevalence of poor feeding (97%, 56/58) and hypotonia among infants. This finding is commonly followed in the neonatal period by poor sucking, swallowing dysfunction, slow feeding, and failure to thrive (Chiu, Leung, Chu, Gripp, & Chung, 2017; Digilio et al, 2008; Gripp et al, 2012; Hiippala et al, 2016; Ioan & Fryns, 2002; Kawame et al, 2003; Nwakalor, Said‐Delgado, Krinshpun, & Velinov, 2021; Piccione et al, 2009; Pratesi et al, 1998; Syu et al, 2022; Vuralli et al, 2020; Weaver et al, 2022) (Table 1) (Box 1).…”