About

Matthew Thomas Whitehead, MD, is an Associate Professor of Radiology at the Children's Hospital of Philadelphia. He is an active member of the Medical Staff at the Hospital of the University of Pennsylvania, Chester County Hospital, and Pennsylvania Hospital, all within the Department of Radiology in Philadelphia. Dr. Whitehead specializes as a Pediatric Neuroradiologist and serves as the Director of Fetal and Neonatal Neuroimaging at the Children's Hospital of Philadelphia. His educational background includes a BS in Biology and Chemistry from the University of Tennessee at Martin and an MD from the University Tennessee College of Medicine. His professional work focuses on pediatric neuroradiology, with research contributions in neuroimaging, developmental milestones, and genetic disorders affecting the nervous system.

Research topics

• Surgery
• Nursing
• Emergency medicine
• Intensive care medicine
• Internal medicine
• Medicine

Selected publications

• <i>PTPN1</i> -related autoinflammation is a common cause of Aicardi-Goutières Syndrome with reduced penetrance

  medRxiv · 2026-04-01

  articleOpen access

  Abstract Purpose Aicardi-Goutières syndrome (AGS) is a type I interferonopathy presently associated with nine genes. PTPN1 is a negative regulator of the interferon pathway previously associated with chronic inflammation and recently type 1 IFN autoinflammation. Methods Genomic data from undiagnosed individuals with suspected AGS were interrogated for PTPN1 variants, and predicted loss-of-function (pLOF) and damaging missense variants in PTPN1 were sought in two additional academic databases as well as the All of Us database. Results We identified 13 cases with ultra-rare heterozygous pLOF or highly damaging missense variants in PTPN1 . Nine cases were identified in a cohort of 53 individuals (∼ 17%) with clinical, imaging and persistent biochemical features of AGS. Median age of onset is 1.75 years (IQR 0.67), significantly later (p&lt; 0.0001) than other AGS genotypes. Four additional cases were identified in academic datasets with variable clinical features suggestive of autoinflammation. Additionally, 49 individuals with ultra-rare, damaging PTPN1 variants were identified in the All of Us database, none had features suggestive of AGS, but autoimmunity was highly prevalent (∼21.6%). Conclusion Our data implicate PTPN1 as a cause of later-onset presentations of AGS within a broader spectrum of autoinflammatory phenotypes. Segregation and biobank data demonstrate reduced penetrance, with carriers being enriched for autoimmune disorders.

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• BLOC1S1 variants cause lysosomal and autophagic defects resulting in a hypomyelinating leukodystrophy with epileptic encephalopathy

  The American Journal of Human Genetics · 2026-03-25 · 1 citations

  article
  PublisherDOI

• Recommendations for structural magnetic resonance imaging in infants with first afebrile seizure or new onset epilepsy: Evidence‐based recommendations from the <scp>ILAE</scp> Neuroimaging Task Force

  Epilepsia · 2026-03-27

  articleOpen access

  Infants aged 1-24 months with new onset epilepsy frequently present with structural brain abnormalities, yet no updated evidence-based magnetic resonance imaging (MRI) guidelines exist for this population. The International League Against Epilepsy (ILAE) Neuroimaging Task Force developed evidence-based recommendations for structural brain MRI in infants with a first afebrile seizure or new onset epilepsy. A multidisciplinary panel defined three PICO (patients, intervention, comparison group, outcome under consideration) questions, conducted a systematic review (PROSPERO [Prospective Register of Systematic Reviews] CRD42024592653), and reported the results in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Risk of bias was evaluated using the JBI (Joanna Briggs Institute) checklist. GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology was used to assess certainty of evidence and formulate recommendations for the following: (1) the effectiveness of MRI in identifying underlying etiologies, (2) clinical predictors of MRI abnormalities, and (3) MRI protocols. Seventeen studies (n = 1209) were included. Among 753 infants who underwent MRI, 438 (58.2%) had abnormal findings. Despite heterogeneity in MRI protocols and reporting, the evidence supports the utility of MRI in this population. Specific clinical features (focal seizure semiology, abnormal neurological examination, seizure duration > 5 min, focal electroencephalographic abnormalities, developmental delay, and perinatal complications) were associated with abnormal MRI findings, although methodological limitations reduce certainty. Only six studies provided data on MRI sequences; however, none reported findings specifically in relation to the diagnostic accuracy or yield of individual protocols, precluding the development of evidence-based recommendations on MRI protocol selection. MRI is conditionally recommended in all infants with a first afebrile seizure or new onset epilepsy. MRI could be prioritized in those with specific clinical features indicative of higher likelihood of abnormal findings. Recommendations are based on very low certainty of evidence. These are the first ILAE-endorsed, evidence-based recommendations for MRI in infants with first afebrile seizure or new onset epilepsy. Further prospective studies with standardized protocols are needed to refine MRI indications and optimize diagnostic yield in this age group.

  PublisherDOI

• Coronal Clival Cleft: Estimated Prevalence and Clinical Associations in a Pediatric Cohort

  American Journal of Neuroradiology · 2026-02-06

  article

  BACKGROUND AND PURPOSE: Coronal clival cleft is a congenital corticated defect traversing the basioccipital portion of the clivus, beneath the spheno-occipital synchondrosis. It has been reported in cases of CHARGE syndrome, Cornelia de Lange syndrome, anencephaly, hemifacial microsomia, Chiari deformities, and in asymptomatic patients, but it may be underdiagnosed and underestimated on imaging. This study aims to estimate the prevalence of coronal clival cleft and expand its genetic and clinical associations. MATERIALS AND METHODS: In this retrospective study, the imaging report database from a single children's hospital was queried for the terms "clival cleft", "clivus cleft", "clefts of the clivus", and "cleft of the clivus". The search was restricted to head and neck, brain, and cervical spine CTs and MRIs. reports from a consecutive 2-year period (May 2022 to June 2024) authored by either of two neuroradiologists with expertise in the diagnosis of clival clefts. Electronic medical records were reviewed for demographics and to confirm final diagnosis and genetic disorders. Descriptive statistics were used to calculate frequency, demographic characteristics, and percentage distribution. RESULTS: , including CHARGE syndrome (n=4), Chiari I deformities (n=2), Cornelia de Lange (n=1), and others (n=6). CONCLUSION: Coronal clival clefts are potentially more common than previously anticipated. Radiologists should be able to recognize and differentiate coronal clival clefts from anatomic variants in the skull base and, when a coronal clival cleft is found, must actively search for additional cerebral and craniovertebral junction abnormalities, often found in combination.

  PublisherDOI

• Neuroimaging Protocols for Pediatric Inherited Metabolic Disorders: Standardization and Future Perspectives Using a Delphi Method

  Open MIND · 2026-01-01

  articleOpen access
  OA PDFDOI

• Cerebellar Malformations in Congenital Cytomegalovirus Infection

  American Journal of Neuroradiology · 2026-03-05

  articleOpen accessSenior author

  <h3>BACKGROUND AND PURPOSE:</h3> Congenital cytomegalovirus (cCMV) is the leading infectious cause of birth defects in the United States; its spectrum of MRI findings is broad, with cerebellar abnormalities scarcely reported in the literature. We aim to describe the neuroimaging spectrum of cerebellar anomalies and malformations in patients with cCMV infection and their associations with other typical cCMV findings in prenatal and postnatal brain MRI. <h3>METHODS:</h3> We conducted a single-center retrospective observational study at a quaternary children’s hospital. Included patients had fetal and/or postnatal brain MRI and confirmed congenital cCMV infection. Age-matched controls were also analyzed. Two neuroradiologists evaluated cerebellar morphology on fetal and postnatal brain MRIs; one determined cerebellar size and documented other common cCMV imaging features. Statistical analyses included paired <i>t</i>-tests, Cohen’s <i>d</i>, McNemar’s, and Chi-square tests, with inter-rater reliability assessed by Cohen’s Kappa and Phi coefficient. <h3>RESULTS:</h3> Seventy-two MRIs (64 patients) were included from 36 CMV+ and 36 controls. In the CMV+ group, 17 MRIs (47.2%) were fetal (median gestational age: 30 weeks [IQR: 23-33.6]), and 19 (52.8%) were postnatal (median age: 4.23 months [IQR: 0.36-11.89]). Eight patients underwent both fetal and postnatal imaging. Cerebellar hemisphere and vermian dysmorphology were seen in 10 fetal MRIs (58.8%). Postnatally, the cerebellar hemispheres were abnormal in 11 (57.9%) MRIs, and the vermis in 9 (47.4%), with dysfolia/dysplasia being the most prevalent malformation (57.9% and 47.4%, respectively). Interrater reliability for identifying cerebellar abnormalities showed moderate agreement (kappa=0.665). Vermis height (p=0.02) and anteroposterior diameter (p&lt;0.001) were smaller in CMV+ postnatal MRIs, but not in fetal studies. All cases with cerebellar abnormalities also had at least one other CMV-related finding (φ =0.581). <h3>CONCLUSION:</h3> cCMV-associated cerebellar malformations are more prevalent than previously reported in the literature. Cerebellar abnormalities were nearly as frequent or more frequent than many of the typically reported cCMV features, and were always found in association with other typical imaging findings. The cerebellum requires careful evaluation in all cases of suspected cCMV.

  PublisherDOI

• P156: PTPN1-related autoinflammation is a common cause of Aicardi Goutières syndrome with reduced penetrance

  Genetics in Medicine Open · 2026-01-01

  articleOpen access

  malformation located in the brain.Thirty children (81%) had either germline or somatic genetic testing, and 16 of these children (53%) had a genetic variant.Thirty-three percent (4/12) who had an AVM and were tested had a positive finding, which were all somatic.Three out of 4 children had a KRAS variant (p.Gly12Asp).One of 4 children had a KRAS variant (p.Gln61His).67% (8/12) who had only a CCM and were tested had a genetic finding, which included germline PDCD10 (1/12) and KRIT1 (4/12), and somatic results including MAP3K3 (2/12) and PIK3CA (2/12).Notable findings include somatic variants in PIK3CA for 2 children with retinoblastoma and CCMs, somatic results for all children with a spinal lesion, and a novel somatic finding in GNAQ (p.Gln209His) for a child with a CCM and spinal hemangioma.Conclusion: Our findings highlight the value of genetic testing for neurological vascular malformations.Expanding access to genetic testing may inform future medical treatments.By describing the somatic variant spectrum in these lesions, we hope to encourage integration of somatic genetic testing into clinical practice and provide information for future targeted molecular therapies.

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• Stratification of Phenotypes in Childhood-Onset <i>COL4A1/COL4A2</i> –Related Disorders Based on Age of Presentation

  Neurology Genetics · 2026-05-04

  articleOpen access

  Background and Objectives: are associated with a multisystem disorder characterized by prominent neurologic involvement that includes intracranial hemorrhages, white matter injury, neurodevelopmental impairment, and epilepsy. The phenotypic spectrum, however, is broad, and disease subgroups have not been robustly identified. The objective of this study was to distinguish pediatric subgroups based on age at symptom onset. Methods: seen at a single center between January 2008 and October 2024. Patients were included if they had likely pathogenic/pathogenic variants or variants of uncertain significance with consistent clinical phenotype and were followed for ≥6 months. Medical records, laboratory data, and neuroimaging were reviewed. Patients were stratified by age at symptom onset into perinatal, early childhood, and late childhood onset (up to 28 days, up to 4 years, and up to 18 years, respectively). Results: patients). Isolated leukoencephalopathy was universally present in late childhood onset patients. Discussion: -related disorder varies by age at disease onset. Perinatal and early childhood presentations (≤4 years) have a prominent neurologic phenotype with severe developmental delays, cerebral palsy, and epilepsy, correlating on imaging with sequelae from brain injury during prenatal brain development. Late childhood presentations (>4 years) have a milder phenotype, typically with isolated leukoencephalopathy on imaging.

  PublisherDOI

• Comment: The fetal taenia-tela choroidea complex is frequently detectable on MRI when it is needed in the differential diagnosis of posterior fossa abnormalities

  Pediatric Radiology · 2026-04-09

  article1st authorCorresponding
  PublisherDOI

• Pontocerebellar hypoplasia: a review from 1912 to 2022

  Brain Communications · 2025-01-01 · 3 citations

  reviewOpen access

  Abstract Pontocerebellar hypoplasia is a rare neurodevelopmental disorder that results from differences in formation and function of the pons, cerebellum and cerebrum. It can be diagnosed prenatally or postnatally with a combination of clinical, neuroimaging and genetic data obtained over time. The diagnosis of pontocerebellar hypoplasia usually portends severe developmental delay, epilepsy and/or neurodegeneration in childhood. Here we perform a comprehensive review with the primary goal of evaluating published evidence addressing the clinical and genetic features of pontocerebellar hypoplasia by type and subtype. Secondly, we summarize neurodiagnostic patterns of pontocerebellar hypoplasia and demonstrate its spectrum. Finally, we provide recommendations in diagnosis, prognosis and management for the neurologist. To address these goals, we performed an extensive review of published literature from 1912 to 2022. We identified 191 publications by combining search results from PubMed, OMIM and cross-referenced bibliographies. Publications on developmental neuroanatomy, not pertaining to pontocerebellar hypoplasia or published in a foreign language were excluded. We performed both qualitative (1912–1993) and quantitative (1993–2022) analyses to understand the current classification of this disease as it pertains to genetic and neurodiagnostic features of pontocerebellar hypoplasia by type and subtype. Our review shows that the most reported types of pontocerebellar hypoplasia are 1, 2 and 6; less frequently described are 3, 4 and 9. Very few cases are described for all other subsequent pontocerebellar hypoplasia types. Mutations in TSEN54, RARS2, EXOSC3 and AMPD2 (genes that regulate RNA processing and basic cellular metabolism) are the most frequently reported pathological mutations in pontocerebellar hypoplasia. The neuroradiographic features of pontocerebellar hypoplasia are complex and evolve over time, affecting the pons, cerebellum, vermis, cortex and cerebral white matter. In conclusion, pontocerebellar hypoplasia is a rare neurodevelopmental disorder, often the result of genetic dysfunction in basic neural metabolism. The diagnosis conveys significant implications for the affected individual and their families and requires a combination of clinical, neuroradiographic, and genetic testing to best inform type/subtype categorization of pontocerebellar hypoplasia.

  PublisherOA PDFDOI

Frequent coauthors

• Asim F. Choudhri

  University of Tennessee Health Science Center

  56 shared

• Andrea Gropman

  Children's National

  43 shared

• Frederick A. Boop

  University of Tennessee Health Science Center

  35 shared

• David M. Mirsky

  University of Colorado Denver

  30 shared

• Kshitij Mankad

  Great Ormond Street Hospital

  27 shared

• Adeline Vanderver

  University of Pennsylvania

  26 shared

• Michael Wien

  University Hospitals of Cleveland

  22 shared

• Jai Sidpra

  Great Ormond Street Hospital

  21 shared