Peter Hammond

Peter Hammond
KU Leuven | ku leuven · Department of Human Genetics

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148
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Publications

Publications (148)
Article
Background In clinical genetics, establishing an accurate nosology requires analysis of variations in both aetiology and the resulting phenotypes. At the phenotypic level, recognising typical facial gestalts has long supported clinical and molecular diagnosis; however, the objective analysis of facial phenotypic variation remains underdeveloped. In...
Article
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Identification and delineation of craniofacial characteristics support the clinical and molecular diagnosis of genetic syndromes. Deep learning (DL) frameworks for syndrome identification from 2D facial images are trained on large clinical datasets using standard convolutional neural networks for classification. In contrast, despite the increased a...
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Monitoring and regulating discharges of wastewater pollution in water bodies in England is the duty of the Environment Agency. Identification and reporting of pollution events from wastewater treatment plants is the duty of operators. Nevertheless, in 2018, over 400 sewage pollution incidents in England were reported by the public. We present novel...
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Recognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-cente...
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Craniofacial dysmorphism is associated with thousands of genetic and environmental disorders. Delineation of salient facial characteristics can guide clinicians towards a correct clinical diagnosis and understanding the pathogenesis of the disorder. Abnormal facial shape might require craniofacial surgical intervention, with the restoration of norm...
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The epilepsies are now conceptualized as network disruptions: focal epilepsies are considered to have network alterations in the hemisphere of seizure onset, whilst generalized epilepsies are considered to have bi-hemispheric network changes. Increasingly, many epilepsies are also considered to be neurodevelopmental disorders, with early changes in...
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A Correction to this paper has been published: https://doi.org/10.1038/s41545-021-00116-3
Article
Background and Objective; Genetic risk factors for childhood cancer may also influence facial morphology. 3D photography can be used in the recognition of differences in face shape among individuals. In previous research, 3D facial photography was used to identify increased facial asymmetry and greater deviation from normal facial morphology in a g...
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Cantú syndrome (CS) was first described in 1982, and is caused by pathogenic variants in ABCC9 and KCNJ8 encoding regulatory and pore forming subunits of ATP-sensitive potassium (KATP ) channels, respectively. It is characterized by congenital hypertrichosis, osteochondrodysplasia, extensive cardiovascular abnormalities and distinctive facial anoma...
Article
Background: Micrognathia occurs isolated and as part of entities like Robin sequence (RS). An objective measurement of mandible size and growth is needed to determine the degree of micrognathia and enable a comparison of treatment outcomes. A pilot study was conducted to investigate the usability of 3-dimensional (3D) facial photogrammetry, a fast...
Article
Background: Since the 1970s, a range of facial, neurostructural, and neurocognitive adverse effects have been shown to be associated with prenatal alcohol exposure. Typically, these effects are studied individually and not in combination. Our objective is to improve the understanding of the teratogenic effects of prenatal alcohol exposure by simul...
Article
Ethanol causes fetal alcohol spectrum disorders (FASD) partly by inhibiting cell adhesion mediated by the L1 neural cell adhesion molecule. Ethanol interacts with an alcohol binding pocket in the L1 extracellular domain (ECD), and dephosphorylation of S1248 in the L1 cytoplasmic domain (CD) renders L1 adhesion insensitive to inhibition by ethanol (...
Article
Prenatal alcohol exposure (PAE) can cause behavioral and brain alterations over the lifespan. In animal models, these effects can occur following PAE confined to critical developmental periods, equivalent to the third and fourth weeks of human gestation, before pregnancy is usually recognized. The current study focuses on PAE during early neurulati...
Article
Background: Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure (PAE) by developing computer based tools for screening facial form. Methods: All 415 individuals considered were evaluated by expert dysmorphologists and categorized as 1) healthy control (HC), 2) fetal alcohol syndrome (FAS) or 3) heavily pren...
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Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder associated with unusual facial features, limb abnormalities, a wide range of health conditions, and intellectual disability. Mutations in five genes that encode (SMC1A, SMC3, RAD21) or regulate (NIPBL, HDAC8) the cohesin complex have been identified in up to 70% of individuals. Gen...
Article
Introduction: Radiotherapy is essential for achieving and maintaining local control in head and neck rhabdomyosarcoma (HNRMS) patients. However, radiotherapy may cause outgrowth disturbances of facial bone and soft tissue, resulting in facial asymmetry. The aim of this study was to develop a method to visualize and measure facial asymmetry in HNRM...
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Introduction Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of significant clinical relevance, as it affects treatment, prognosis and facilitates genetic counselling. Previous studies revealed that only half of the known TPSs are recognised during standard paediatric cancer care. In current medical practice...
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Background: Midface hypoplasia as exemplified by Treacher Collins Syndrome (TCS) can impair appearance and function. Reconstruction involves multiple invasive surgeries with variable long-term outcomes. This study aims to describe normal and dysmorphic midface postnatal development through combined modelling of skeletal and soft tissues and to dev...
Article
A group of patients who had cancer as a child were previously found to have distinct patterns of morphological abnormalities. In this study, we investigated the added value of 3D shape analysis to characterize their facial morphology. Primarily, we showed in an objective and quantitative manner that the overall facial dysmorphism of the individuals...
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Sequencing technology is increasingly demonstrating the impact of genomic copy number variation (CNV) on phenotypes. Opposing variation in growth, head size, cognition and behaviour is known to result from deletions and reciprocal duplications of some genomic regions. We propose normative inversion of face shape, opposing difference from a matched...
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3D analysis of facial morphology has delineated facial phenotypes in many medical conditions and detected fine grained differences between typical and atypical patients to inform genotype-phenotype studies. Next-generation sequencing techniques have enabled extremely detailed genotype-phenotype correlative analysis. Such comparisons typically emplo...
Article
Wolf-Hirschhorn syndrome (WHS) is a complex genetic disorder caused by the loss of genomic material from the short arm of chromosome 4. Genotype-phenotype correlation studies indicated that the loss of genes within 4p16.3 is necessary for expression of the core features of the phenotype. Within this region, haploinsufficiency of the genes WHSC1 and...
Article
Prader-Willi syndrome is a neurodevelopmental disorder resulting from the absence of expression of paternally expressed gene(s) in a highly imprinted region of chromosome 15q11-13. The physical phenotype includes evidence of growth retardation due to relative growth hormone deficiency, small hands and feet, a failure of normal secondary sexual deve...
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Classic facial characteristics of fetal alcohol syndrome (FAS) are shortened palpebral fissures, smooth philtrum, and thin upper vermillion. We aim to help pediatricians detect facial dysmorphism across the fetal alcohol spectrum, especially among nonsyndromal heavily exposed (HE) individuals without classic facial characteristics. Of 192 Cape Colo...
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Polycystin 2 (Pkd2) that belongs to the TRP family, which plays a critical role in development. Pkd2 is mainly localized in the primary cilia that also function as mechanoreceptors in many cells that influence multiple biological processes including Ca2+ influx, chemical activity and signalling pathways. Mutations in many cilia proteins result in c...
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The extracellular signal-related kinases 1 and 2 (ERK1/2) are key proteins mediating mitogen-activated protein kinase signaling downstream of RAS: phosphorylation of ERK1/2 leads to nuclear uptake and modulation of multiple targets. Here, we show that reduced dosage of ERF, which encodes an inhibitory ETS transcription factor directly bound by ERK1...
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For a disorder as common as fragile X syndrome, the most common hereditary form of cognitive impairment, the facial features are relatively ill defined. An elongated face and prominent ears are the most commonly accepted dysmorphic hallmarks. We analysed 3D facial photographs of 51 males and 15 females with full FMR1 mutations and 9 females with a...
Article
Wolf-Hirschhorn syndrome is a well-known clinical entity caused by a terminal deletion of the short arm of chromosome 4 (4p-). The diagnosis is usually made in childhood because of the pathognomonic facial dysmorphism, multi-organ involvement and seizures. Epilepsy is a major medical complication during the first years of life, with seizures typica...
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Many pathogenic structural variants of the human genome are known to cause facial dysmorphism. During the past decade, pathogenic structural variants have also been found to be an important class of genetic risk factor for epilepsy. In other fields, face shape has been assessed objectively using 3D stereophotogrammetry and dense surface models. We...
Article
22q11.2 deletion syndrome (22q11DS) has a complex phenotype with more than 180 characteristics, including cardiac anomalies, cleft palate, intellectual disabilities, a typical facial morphology, and mental health problems. However, the variable phenotype makes it difficult to predict clinical outcome, such as the high prevalence of psychosis among...
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Prenatal ethanol exposure is the leading preventable cause of congenital mental disability. Whereas a diagnosis of fetal alcohol syndrome (FAS) requires identification of a specific pattern of craniofacial dysmorphology, most individuals with behavioral and neurological sequelae of heavy prenatal ethanol exposure do not exhibit these defining facia...
Data
Morphing illustrates unique facial phenotypes in each ethanol exposure group. Rapidly interpolated images provide dynamic morphs between mean control (WT) and mean ethanol-exposed facial surfaces in portrait and profile view. (GIF)
Data
Morphing illustrates unique brain and facial phenotypes in each ethanol exposure group. Rapidly interpolated images provide dynamic morphs between the mean control (WT) and mean ethanol-exposed brain and facial surfaces from a superior (downward at the snout) and inferior (upward at the mandible) view. (GIF)
Data
Morphing illustrates opposing changes in brain region shape between ethanol exposure groups. Rapidly interpolated images provide dynamic morphs between the mean GD7 exposure group and the mean GD8.5 exposure group from a posterior-oblique view. (GIF)
Data
Landmarks used for DSM analysis of selected brain regions are shown in superior and inferior views. (TIF)
Data
Stage-specific ethanol exposure causes varying degrees of ocular defects. Prior to fixation of vehicle and ethanol exposed fetuses for MRM, both eyes were imaged by bright-field microscopy. Ocular defects were rated on a scale from 1–5 as follows: (1) normal; (2) slight microphthalmia or slight pupil shape abnormality; (3) slight microphthalmia and...
Data
Volumetric analysis of individual brain regions in control and ethanol exposure groups. Individual brain region volumes were derived from manual segmentation. To determine disproportionate differences, the volume of each region was calculated as a percentage of total brain volume in each animal. Paired structures are shown individually. Letters abo...
Data
Linear brain measurements of entire populations reflect volumetric and DSM results. Linear measurements were produced from transverse MRM sections at the level of the anterior commissure in all scanned animals. Biparietal diameter, spanning the widest distance across the cerebrum, third ventricular width (TVW), and septal region width (SRW) were me...
Data
3D visualization of face-brain dysmorphology resulting from stage-specific ethanol exposure. For the animals shown in Figure 7, the brain and face are visualized concurrently in 3D by reducing head surface opacity using Slicer3, an open source image visualization platform (www.slicer.org). (WMV)
Conference Paper
Objective: Mice with a conditional knock-out of the Pkd2 gene in neural-crest derived tissues have a severe postnatal craniofacial phenotype. In these animals, the craniofacial abnormalities appear after birth in regions subjected to mechanical stress. Interestingly, Pkd2 is involved in autosomic dominant polycystic kidney disease (ADPKD), the mo...
Article
Fibrodysplasia ossificans progressiva (FOP) causes extensive heterotopic bone formation due to heterozygous mutations in the glycine-serine activation domain of ACVR1 (ALK2), a bone morphogenetic protein type I receptor. Anecdotal observations of facial similarity have been made by clinicians and parents, but no objective quantitative analysis of t...
Article
Most cases of apparently idiopathic hypertrophic cardiomyopathy (HCM) in children are caused by mutations in cardiac sarcomere protein genes. HCM also commonly occurs as an associated feature in some patients with disorders caused by mutations in genes encoding components of the RAS-mitogen activated protein kinase (MAPK) signaling pathway. Althoug...
Article
Abnormal phenotypes have played significant roles in the discovery of gene function, but organized collection of phenotype data has been overshadowed by developments in sequencing technology. In order to study phenotypes systematically, large-scale projects with standardized objective assessment across populations are considered necessary. The repo...
Article
It is generally accepted that the facial phenotype of Wolf-Hirschhorn syndrome is caused by deletions of either Wolf-Hirschhorn critical regions 1 or 2 (WHSCR 1-2). Here, we identify a 432 kb deletion located 600 kb proximal to both WHSCR1-2 in a patient with a WHS facial phenotype. Seven genes are underlying this deletion region including FAM193a,...
Article
Dravet syndrome has been found recently as an important underlying condition in cases of alleged vaccine encephalopathy after pertussis vaccination, where vaccination seemed to have precipitated the occurrence of the disease without modifying the long-term course. We report on a patient diagnosed with Angelman syndrome in her fifth decade, in whom...
Data
PROS1 copy number analysis by quantitative PCR. Results of PROS1 copy number analysis by quantitative PCR analysis. RQ -relative quantity. (TIF)
Data
Hippocampal sclerosis in Case 3. (A) T1-weighted magnetic resonance imaging of the Case 3 revealed right hippocampal volume loss (arrow) compatible with hippocampal sclerosis. (B) Histopathology of the lobectomy specimen from Case 3 confirmed hippocampal sclerosis, without mossy fibre sprouting. There was neuronal loss in CA1, CA4 and gliosis on GF...
Data
Dense surface morphology (DSM) results for Case 1 and Case 2. (A) The scatter plot shows age (horizontally) against DSM distance (vertically) between the matched mean face and the patient and 200 control faces. Distance from the patient-matched mean face was linearly regressed against age for all controls. The patient was fitted to the appropriate...
Data
Dynamic profiles of glucose, insulin, and other carnitine esters. Dynamic profiles of glucose, insulin, and other carnitine esters. NEFA - non-esterified fatty acids.NEFA - non-esterified fatty acids. (TIF)
Data
Animations of face morphs. Animations of face morphs offer the best visualisation of face shape differences when comparing each case and its age/sex-matched mean face. The unusual narrowness of Case 3's face is dysmorphic. S1 - Case 1. (WMV)
Data
Animations of face morphs. Animations of face morphs offer the best visualisation of face shape differences when comparing each case and its age/sex-matched mean face. The unusual narrowness of Case 3's face is dysmorphic. S2 - Case 2. (WMV)
Data
Animations of face morphs. Animations of face morphs offer the best visualisation of face shape differences when comparing each case and its age/sex-matched mean face. The unusual narrowness of Case 3's face is dysmorphic. S3 - Case3. (WMV)
Article
Full-text available
Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained. We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic microdeletions were found during a study of genetic...
Article
Full-text available
Wolf-Hirschhorn syndrome is caused by anomalies of the short arm of chromosome 4. About 55% of cases are due to de novo terminal deletions, 40% from unbalanced translocations and 5% from other abnormalities. The facial phenotype is characterized by hypertelorism, protruding eyes, prominent glabella, broad nasal bridge and short philtrum. We used de...
Article
The face and brain normally develop in a coordinated fashion under the influence of many genes. Hence, genetic anomalies disrupting early development can result both in cognitive impairment and facial dysmorphology, the latter often being an important clue to a preliminary diagnosis. Recent advances in computational models of facial dysmorphology c...
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Craniofacial defects involving the lip and/or palate are among the most common human birth defects. X-linked cleft palate and ankyloglossia results from loss-of-function mutations in the gene encoding the T-box transcription factor TBX22. Further studies show that TBX22 mutations are also found in around 5% of non-syndromic cleft palate patients. A...
Article
We describe a recessively inherited frontonasal malformation characterized by a distinctive facial appearance, with hypertelorism, wide nasal bridge, short nasal ridge, bifid nasal tip, broad columella, widely separated slit-like nares, long philtrum with prominent bilateral swellings, and midline notch in the upper lip and alveolus. Additional rec...
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The heterogeneity of autism spectrum disorders (ASDs) confounds attempts to identify causes and pathogenesis. Identifiable endophenotypes and reliable biomarkers within ASDs would help to focus molecular research and uncover genetic causes and developmental mechanisms. We used dense surface-modelling techniques to compare the facial morphology of 7...