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. 2013 Apr 27:8:63.
doi: 10.1186/1750-1172-8-63.

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Sarah M Nikkel, Andrew Dauber, Sonja de Munnik, Meghan Connolly, Rebecca L Hood, Oana Caluseriu, Jane Hurst, Usha Kini, Malgorzata J M Nowaczyk, Alexandra Afenjar, Beate Albrecht, Judith E Allanson, Paolo Balestri, Tawfeg Ben-Omran, Francesco Brancati, Isabel Cordeiro, Bruna Santos da Cunha, Louisa A Delaney, Anne Destrée, David Fitzpatrick, Francesca Forzano, Neeti Ghali, Greta Gillies, Katerina Harwood, Yvonne M C Hendriks, Delphine Héron, Alexander Hoischen, Engela Magdalena Honey, Lies H Hoefsloot, Jennifer Ibrahim, Claire M Jacob, Sarina G Kant, Chong Ae Kim, Edwin P Kirk, Nine V A M Knoers, Didier Lacombe, Chung Lee, Ivan F M Lo, Luiza S Lucas, Francesca Mari, Veronica Mericq, Jukka S Moilanen, Sanne Traasdahl Møller, Stephanie Moortgat, Daniela T Pilz, Kate Pope, Susan Price, Alessandra Renieri, Joaquim Sá, Jeroen Schoots, Elizabeth L Silveira, Marleen E H Simon, Anne Slavotinek, I Karen Temple, Ineke van der Burgt, Bert B A de Vries, James D Weisfeld-Adams, Margo L Whiteford, Dagmar Wierczorek, Jan M Wit, Connie Fung On Yee, Chandree L Beaulieu; FORGE Canada Consortium; Sue M White, Dennis E Bulman, Ernie Bongers, Han Brunner, Murray Feingold, Kym M Boycott
Collaborators

The phenotype of Floating-Harbor syndrome: clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Sarah M Nikkel et al. Orphanet J Rare Dis. .

Abstract

Background: Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.

Methods and results: Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.

Conclusions: This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.

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Figures

Figure 1
Figure 1
Facial photographs of 6 females with FHS with the common Arg2444* mutation.
Figure 2
Figure 2
Facial photographs of 4 individuals with FHS of varying ages with the Arg2435* mutation.
Figure 3
Figure 3
Facial photographs of 7 individuals with FHS as examples of the other mutations. A. A female with the Gln2407* mutation. B. A male with the Ala2440fs*3 mutation. C. A female with the Asn2618fs*11 mutation. D. A female and male with the Pro2459fs*125 mutation. E. A mother and daughter with the Arg2748* mutation.
Figure 4
Figure 4
Hands and feet of individuals with FHS. Clinical photos demonstrating the variability of features ranging from unremarkable to brachydactyly, short broad thumbs and big toes, broad fingertips.
Figure 5
Figure 5
Birth weights of individuals with FHS. Male birth weights - blue dots; Female birth weights – pink dots. The mean, 5th and 95th confidence intervals are indicated.
Figure 6
Figure 6
Height and weight of female individuals with FHS. Each point represents a single individual’s measurements at the time of data collection.
Figure 7
Figure 7
Height and weight of male individuals with FHS. Each point represents a single individual’s measurements at the time of data collection.
Figure 8
Figure 8
OFCs of females with FHS. Each point represents a single individual’s measurements at the time of data collection. The mean, 5th and 95th confidence intervals are indicated.
Figure 9
Figure 9
OFCs of males with FHS. Each point represents a single individual’s measurements at the time of data collection. The mean, 5th and 95th confidence intervals are indicated.
Figure 10
Figure 10
Bone age values plotted against chronological age for 25 individuals with FHS.
See this image and copyright information in PMC

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