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Professor Peter Hammond

Google Scholar Publication List: URL: http://tinyurl.com/bylu5hu

3D Shape Analysis of Typical and Atypical Neuro-Facial Growth and Development

My main research focus is in craniofacial dysmorphism and the development of mathematical techniques and software tools for 3D dense surface model (DSM) analysis (Hammond, 2007). We have analysed 3D facial photographs to delineate facial dysmorphism in individuals with genetic conditions such as Noonan, Smith-Magenis, Williams and 22q11 del syndromes (Hammond et al, 2004 & 2005), Cornelia de Lange syndrome (Bhuiyan et al, 2006), and Wolf-Hirschhorn syndrome (Hammond et al, 2012; Hannes et al, 2012).

DSM techniques have been applied to several image modalities to study affected children and associated animal models to identify:

• the role of GT2FIRD1 in craniofacial dysmorphism in Williams syndrome (Tassabehji et al, 2005) using 3D photographs and 3D micro-CT images

• the role of neural crest migration in craniofacial dysmorphism in Bardet–Biedl syndrome (Tobin et al, 2008) using 3D facial photos and 3D laser scans

• novel craniofacial differences in Fragile X syndrome (Heulens et al, 2012) using 3D facial photos and 3D micro-CT images

  
  

  
  

The Fragile X syndrome study also involved novel signature graph techniques recently developed (Hammond and Suttie, 2012) while I was on a sabbatical at the Wetherall Institute of Molecular Medicine in Oxford kindly hosted by Professor Andrew Wilkie. These new techniques were developed specifically to address the paucity of subjects available for studies of rare genetic disorders. Provided sufficient healthy subjects are available to normalize facial form, individual and small numbers of children with extremely rare conditions, such as Fibrodysplasia Ossificance Progressiva (Hammond et al, 2012), can be analyzed.

A recently published application of the signature graph techniques was in a mouse model of fetal alcohol syndrome where 3D MRI images were used to show that face-brain effects vary in relation to timing of ethanol exposure (Lipinski et al, 2012). A study of fetal alcohol spectrum disorder in children describes how pediatricians might use the software tools we have developed to visualize atypical face shape. We have also demonstrated links between facial dysmorphism and neurocognitive performance in fetal alcohol syndrome (Suttie et al, 2012).

morph between mean faces of controls and children diagnosed with fetal alcohol syndrome

More recent work on face-brain-behaviour effects began with autism spectrum disorders (Hammond et al, 2007) and has continued more recently with 22q11 deletion syndrome (Sindeberry et al, 2012). A further broadening of face-brain applications, in conjunction with Professor Sanjay Sisodiya of UCL’s Institute of Neurology, has used atypical face shape in epilepsy to identify co-morbidity (Kasperavičiūtė et al, 2011; Novy et al, 2012)and genomic structural variants (Chinthapalli et al, 2012).

These techniques and their application are being developed further in a part-time PhD programme by research assistant Mike Suttie.

Computational models of cell behaviour

A second more recent thread to my research is mathematical and computational models of cell-cell and cell-collagen interactions. The former arose from collaborations with oral biologists interested in understanding oral cancer (Maheswaran et al, 2007). The latter is a collaboration with Professor Paul Riley (formerly UCL and now Oxford Univ) in co-supervising a PhD student, Abbygail Shaw, who is building a model of scar formation in the heart following myocardial infarction.

Relevant publications

Bhuiyan Z, Klein M, Hammond P, van Haeringen A, Mannens M, Van Berckelaer-Onnes I, and Hennekam (2006) Clinical, Molecular, and Behavioural Phenotype Correlations of 39 Patients with Cornelia de Lange Syndrome: The Dutch Experience J Med Genet 43:568-575. doi:10.1136/jmg.2005.038240

Chinthapalli K, Bartolini Ei, Novy J, Suttie M, Marini C, Falchi M, Fox Z, Clayton LMS, Sander JW, Guerrini R, Depondt C, Hennekam R, Hammond P, Sisodiya SMS. (2012) Atypical face shape and genomic structural variants in epilepsy. Brain, in press.

Cox-Brinkman J, Vedder A, Hollak C, Richfield L, Mehta A, Orteu K, Wijburg F, Hammond P (2007) 3D Face Shape in Fabry Disease Eur J Hum Gen 15(5):535-42. doi:10.1038/sj.ejhg.5201798

Hammond P. The use of 3D face shape modelling in dysmorphology. (2007) Arch Dis Child 92:1120-1126. doi:10.1136/adc.2006.103507

Hammond P, Hutton TJ, Allanson JE, Campbell LE, Hennekam RCM, Holden S. Murphy KC, Patton MA, Shaw A, Temple IK, Trotter M, Winter RM. (2004) 3D Analysis of Facial Morphology. Am J Med Gen 126A (4):339 - 348. doi:10.1002/ajmg.a.20665

Hammond P, Hutton TJ, Allanson J, Buxton B, Campbell L, Clayton-Smith J, Donnai D, Karmiloff-Smith A, Metcalfe K, Murphy KC, Patton M, Pober B, Prescott K, Shaw A, Scambler, Smith ACM, Temple K. Hennekam R, Tassabehji M. (2005) Discriminating Power of Localised 3D Facial Morphology. Am J Hum Genet 77:999-1010. doi:10.1086/498396

Hammond P, Forster-Gibson C, Chudley AE, Allanson JE, Hutton TJ, Holden JJA, Lewis MES (2008) Face-brain asymmetry in autism spectrum disorders, Mol Psych 13: 614-623. doi:10.1038/mp.2008.18

Hammond P, Hannes F, Suttie M, Devriendt K, Vermeesch JR, Faravelli F, Forzano F, Parekh S, Williams S, McMullan D, South ST, Carey JC, Quarrell O. (2012a) Fine grained facial phenotyping in Wolf-Hirschhorn Syndrome. Eur J Hum Genet 20 (1), 33-40. doi:10.1038/ejhg.2011.135.

Hammond P, Suttie M, Hennekam RC, Allanson J, Shore EM, Kaplan FS (2012b) The face signature of fibrodysplasia ossificans progressiva. Am J Med Genet A 158A(6):1368-80. 1368-1380. doi:10.1002/ajmg.a.35346

Hammond P, Suttie M. Large scale objective phenotyping of facial morphology in 3D (2012) Hum Mut 33(5):817-25. doi:10.1002/humu.22054

Hannes F, Hammond P, Quarrell O, Fryns J-P, Devriendt K, and Vermeesch JR. (2012) A microdeletion proximal of the critical deletion region is associated with mild Wolf–Hirschhorn syndrome. Am J Med Genet A 158A (5), 996-1004. doi:10.1002/ajmg.a.35299.

Heulens I, Suttie M, Postnov A, De Clerck N3, Perrotta CS, Mattina T, Faravelli F, ForzanoF, Kooy RF, Hammond P (2012) Craniofacial characteristics of Fragile X syndrome in mouse and man, Eur J Hum Gen, in press.

Kasperavičiūtė D, Catarino CB, Chinthapalli K, Clayton LMS, ThomM, Martinian L, Cohen H, Adalat S, Bockenhauer D, Pope S, Lench N, Koltzenburg N, Duncan JS, Hammond P, Hennekam RCM, Land JM, Sisodiya S. (2011) Uncovering Genomic Causes of Co-morbidity in Epilepsy: Gene-driven phenotypic characterization of rare micro-deletions. PLOS ONE 6(8):e23182. doi:10.1371/journal.pone.0023182

Lipinski RJ, Hammond P, O’Leary-Moore SK, Ament JJ, Pecevich SJ, Jiang Y, Budin F, Parnell SE, Suttie M, Godin EA,Everson JL, Dehart DB, Oguz I, Holloway HT, Styner M, Johnson GA, and Sulik KK. Stage-specific ethanol exposure causes unique face-brain dysmorphology patterns in a mouse model of fetal alcohol spectrum disorder. PLOS ONE, in press.

Maheswaran, S., Speight, P. M., & Hammond, P. (2007). Modeling epithelial cell behavior and organization. IEEE Trans Nanobioscience, 6 (1), 77-85.

Novy J, Catarino CB, Chinthapalli K, Smith SM, Clayton-Smith J, Hennekam R, Hammond P, Sisodiya SM. (2012) Another cause of vaccine encephalopathy: A case of Angelman syndrome. Eur J Med Gen, 55 (5), 338-341. doi:10.1016/j.ejmg.2012.01.008.

Sinderberry B, BrownS, Hammond P, Stevens AF, Schall U, Murphy DG, Murphy KC, Campbell L. (2012) Subtypes in 22q11.2 deletion syndrome associated with behaviour and neurofacial morphology. Res in Dev Disab, in press.

Suttie M, Foroud T, Wetherill L, Jacobson S, Jacobson JL, Molteno CD, Hoyme HE, Riley E, Hammond P. (2012) Facial dysmorphism across the fetal alcohol spectrum, under review.

Tassabehji M, Hammond P, Karmiloff-Smith A, Thompson P, Durkin ME, Thorgeirsson S, Metcalfe K, Rucka A, Hutton T, Hogan T, Stewart H, Read A, Maconochie A, and Donnai D. (2005) GTF2IRD1 in Craniofacial Development of Humans and Mice. Science 310(5751):1184-7. doi:10.1126/science.1116142

Tobin JL, DiFranco M, Eichers E, May-Simera H, Garcia M, Yan J, Justice M, Briscoe J, Mayor R, Lupski JR, Hammond P, Beales PL. (2008) Inhibition of neural crest migration underlies craniofacial dysmorphology and Hirschsprung’s disease in Bardet–Biedl syndrome PNAS 6;105(18):6714-9. doi:10.1073/pnas.0707057105

Twigg, S. R. F., Versnel, S. L., Nurnberg, G., Lees, M. M., Bhat, M., Hammond, P, Wilkie, A. O. M. (2009). Frontorhiny, a Distinctive Presentation of Frontonasal Dysplasia Caused by Recessive Mutations in the ALX3 Homeobox Gene. Am J Hum Gen, 84 (5), 698-705. doi:10.1016/j.ajhg.2009.04.009

Organisations who have funded our research

• Newlife

• National Institute for Alcohol Abuse and Addiction (USA)

• Wellcome Trust (UK)

Prof. Peter Hammond

PUW Room M1, Molecular Medicine Unit

UCL Institute of Child Health

30 Guilford Street, London

WC1N 1EH UK

Tel: +44 (0) 20 7905 2399

Fax: +44 (0) 20 7404 6191

Email: p.hammond@ucl.ac.uk