Effects of long-term growth hormone therapy in a girl with Floating-Harbor syndrome

Abstract

Floating-Harbor syndrome is a rare autosomal dominant disorder that presents with short stature, facial dysmorphism, significantly delayed bone age, skeletal abnormalities, speech and language problems, and intellectual disabilities. Although short stature is one of the main clinical manifestations, use of growth hormone therapy in Floating-Harbor syndrome patients has been limited. Only a few reports have investigated the response to growth hormone therapy with regard to final adult height. We report the case of a 7-year-old girl with Floating-Harbor syndrome and a heterozygous mutation, c.7330C > T (p.Arg2444*), in the SRCAP gene. The patient exhibited dysmorphic facial features, severe intellectual disabilities, obsessive-compulsive and aggressive behaviors, and short stature without growth hormone deficiency. Her height standard deviation score improved after 55 months of growth hormone therapy.

Molecular Genetics and Pathogenesis of the Floating Harbor Syndrome: Case Report of Long-Term Growth Hormone Treatment and a Literature Review

“…It has been hypothesized that FHS phenotype is caused by defects in signaling downstream of IGF-1 and not by a decrease in either GH or IGF-1 secretion and/or activity itself. This hypothesis is supported by previous studies that showed limited GH efficacy in FHS ( Son et al (2020) ).…”

“…We have systematically reviewed all published studies describing the spectrum of identified mutations in FHS patients. These studies include patients from various countries, including the United States ( Homma et al (2019) ), China ( Zhang et al (2019) ), South Korea ( Son et al (2020) ) Japan ( Nagasaki et al (2014) ), and others. The results of this analysis are presented in Table 2 .…”

“…FHS patients typically display progressive short stature. The delay in prenatal development is frequently observed ( Son et al (2020) ; García et al (2012) ; Homma et al (2019) ). As detailed previously, height and weight of our proband at birth were normal; and pronounced growth delay and partial growth hormone deficiency were detected in childhood.…”

“…FHS is characterized with typical facial dysmorphologies, anomalies of bone development, speech, intellectual disability, and abnormal growth features ( Pelletier and Feingold (1973) ; Leisti et al (1975) ; Patton et al (1991) ; Lacombe et al (1995) ). Several dozen FHS patients have so far been reported worldwide, with 24 different causal genetic variants discovered ( Son et al (2020) ).…”

“…One of the main phenotypic manifestations of FHS is the short stature and the delay in bone age, though only a few patients with efficient growth hormone treatment have been reported ( Son et al (2020) ; Seifert et al (2014) ; Galli-Tsinopoulou et al (2011) ; García et al (2012) ; Homma et al (2019) ; Stagi et al (2007) ). FHS patients frequently display low levels of stimulated somatotropin (STH), likely influencing the development of a short stature ( Galli-Tsinopoulou et al (2011) ; Cannavò et al (2002) ).…”