Background: Floating-Harbor syndrome(FHS) is a rare autosomal dominant genetic disorder associated with heterozygous mutations in SRCAP gene. The SRCAP protein activates the cAMP-response element binding protein-binding protein(CREBBP) gene that is involved in the regulation of cell growth and division.
Objective: To report on long-term follow-up data of a boy with FHS
Methods: We perform targeted exome sequencing to diagnose FHS
Patient: The boy was born to nonconsanguineous parents of Chinese Han ethnicity at 38 weeks of gestation with birth weight of 2.4kg, 46cm in length. His parents and sister were clinically normal. He presented with failure to thrive, delayed motor development and micropenis(stretched penile length of 2.1cm) at age of one. His gross without support at 10 months of age and walking alone at 24 months of age), while language development was severely retarded (only a few words spoken at 5.5 years of age). At age of one year, he showed proportionate short stature with a length of 67 cm [<-2 SD), a weight of 6.7 kg(<-2 SD). He had dysmorphic facial features: a triangularly-shaped face, deep-set eyes, long eyelashes, lowest malformed ears (hypoplastic helix, small ear lobe), a long nose with narrow bridge, a short philtrum, thin lips, microdontia and malocclusion. Karytype was 46XY, Cerebral MRI showed a very thin pituitary stalk, an absent posterior pituitary. He developed mental retardation and attended an unusual elementary school at 6.5yrs. From 4.83 years old, he was treated with growth hormone (GH) (0.37mg/kg/week) for the indication of short stature born small for gestational age. During the 51 months' GH treatment(0.37~0.46 mg/kg/week) with the 80% adherence,his height SD increased from -4.1SD to -2.57SD, indicating partial GH's growth promoting effect on large SGA dose. The bone age was 4 years delay at age of 9 years at last follow-up. At age of 7, We performed targeted exome sequencing, considering several syndromes with similar phenotypes. An identified variant was confirmed by Sanger sequencing of the patient and his parents. Finally, the patient was confirmed as the FHS with a novel SRCAP mutation[Exon34: c.7245_7246delAT; p.(Ser2416fs)], which is a frameshift mutation resulting in early termination of the protein; it was not found in either of his healthy parents or a control population.
Conclusion: We present a boy with FHS with a novel SRCAP mutation. Our data imply that GH therapy exerted partial effect on the growth.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology