Sung Andrew,  Weiss Brian,  Trout Andrew

Final Pr. ID: Paper #: 147

Despite significant advances in delivering dose-intensive and myeloablative therapy with hematopoietic stem cell support, the survival for patients presenting with metastatic neuroblastoma remains poor, with a 3 year event free survival (EFS) of about 60%. Modern treatment protocols are based on risk stratification which incorporates age of diagnosis, tumor stage, tumor histology, and molecular and cytogenetics including MYCN amplification. ¹⁸F-FDG PET/CT can play a role in disease staging and follow up. The purpose of this study was to report FDG PET findings in a cohort of children with neuroblastoma and assess for predictive associations with MYCN amplification status. Read More

Authors:  Sung Andrew , Weiss Brian , Trout Andrew

Keywords:  Neuroblastoma, PET, Genetics

Germaine Colton,  Richards Allyson,  Tocchio Shannon

Final Pr. ID: Poster #: CR-035

Congenital insensitivity to pain (CIP) is a rare genetic condition in which patients are born with the absence of nociception at birth. These patients do not feel painful or noxious stimuli including pain from infection, inflammation or heat. The inability to feel and respond to painful stimuli leads to repeated injuries and infections, as well as poor wound healing. Children born with CIP are often misdiagnosed as being victims of abuse due to the nature and repetitiveness of their injuries. While rare, it is essential to understand the distinguishing features of CIP and how it differs from non-accidental trauma (NAT). In this case presentation, we provide an overview of the types of fractures and injuries common in patients with CIP, review characteristic imaging findings of CIP and discuss pitfalls specific to radiology.

CONTENT ORGANIZATION:
1) Overview and epidemiology of CIP.
2) Imaging findings characteristic of CIP.
3) Other clinical findings and injuries specific for CIP.
4) Differentiating CIP from NAT.
5) Review follow-up imaging considerations and discuss a radiologist’s role in managing a patient with CIP.

SUMMARY:
1) The major teaching points of this case presentation include:
2) Understanding the clinical presentation and distinguishing imaging findings common in CIP.
3) Recognizing CIP and differentiating it from other types of accidental vs non-accidental trauma is an essential component in patients receiving appropriate care.
4) Providing the correct recommendations for imaging follow-up helps provide improved care to patients with CIP. Read More

Authors:  Germaine Colton , Richards Allyson , Tocchio Shannon

Keywords:  Genetics, Non-Accidental Trauma, Infection

Hook Marcus,  Higgins Timothy,  Hildebrand Andrea,  Sussman Betsy,  Burke Leah

Final Pr. ID: Poster #: EDU-051

Objectives:
1. Present the use of a published algorithm for the evaluation and diagnosis of the pediatric patient with congenital skeletal dysplasia and abnormal skeletal survey.
2. Review usefulness of accurate, narrowed differential diagnosis or suspected single diagnosis in terms of confirmatory testing, treatment implications, and genetic counseling.
3. Demonstrate the utility of the algorithm when applied to recent, rare cases of congenital skeletal dysplasia at our institution, a tertiary trauma center and children’s hospital in the Northeastern United States.

Content:
We present a refined, algorithm-based approach to the evaluation and diagnosis of the pediatric patient with congenital skeletal dysplasia and abnormal skeletal survey. The algorithm optimizes evaluation of the skeletal survey in cases of congenital skeletal dysplasia, aiding in timely, accurate diagnosis. The utility of the refined algorithm is demonstrated as it was applied to recent, confirmed cases of rare skeletal dysplasias at our institution, including metatropic dysplasia and cleidocranial dysplasia.

Teaching Message:
Evaluation of the pediatric patient with congenital skeletal dysplasia and abnormal skeletal survey can be challenging, even for the subspecialty-trained radiologist. By assessing the presence or absence of discriminating imaging features and findings on skeletal survey, the interpreting radiologist can significantly shorten the differential diagnosis or in many cases suggest a single, most-likely primary diagnosis. Narrowing the differential diagnosis is helpful in guiding confirmatory molecular or genetic testing. Timely, accurate diagnosis may have significant treatment and prognostic implications for patients and their families. Read More

Authors:  Hook Marcus , Higgins Timothy , Hildebrand Andrea , Sussman Betsy , Burke Leah

Keywords:  genetic, dysostosis, dwarfism

Sahu Asutosh,  Tripathy Priyadarshini,  Kandemirli Sedat,  Prabhu Sanjay

Final Pr. ID: Poster #: EDU-096

To illustrate the developmental, genetic, and imaging spectrum of malformations of cortical development (MCD) from fetal life through adolescence by integrating principles of normal corticogenesis, key genetic pathways, and evolving MRI patterns.
This exhibit emphasizes:
1. Normal neuronal proliferation, migration, and post-migrational organization.
2. Developmental stage–specific MRI features linked to corresponding disruptions in these processes.
3. Major molecular pathways (LIS1/DCX, TUBB2B, MCPH1, CDK6, PIK3, PTEN, HEPACAM, mTOR) associated with characteristic imaging phenotypes.
4. The role of longitudinal imaging in evaluating cortical maturation, prognosis, and presurgical planning. Read More

Authors:  Sahu Asutosh , Tripathy Priyadarshini , Kandemirli Sedat , Prabhu Sanjay

Keywords:  Magnetic Resonance Imaging, Genetics, Epilepsy

Martinez-sicari Jorge,  Shahid Mehreen,  Mahdi Eman,  Canissario Ryan,  Richard Hope,  Sisler India,  Jones Kathryn,  Mishra Chakradhar,  Vorona Gregory

Final Pr. ID: Poster #: CR-042

Fanconi anemia (FA) is a rare genetic disorder characterized by impaired DNA repair, leading to bone marrow failure, physical abnormalities, and a heightened cancer risk. A severe neurological complication, Fanconi anemia neuroinflammatory syndrome (FANS), involves progressive neuroinflammation and brain lesions, resulting in cognitive and motor impairments. We present the case of a 12-year-old male with FANS and its neuroimaging findings over an 8-year period.

The patient, with a history of stem cell transplant and graft-versus-host disease, initially presented with developmental delays at age 10, progressing to slurred speech and diplopia by age 12. Serial brain MRIs from 2016 to 2024 revealed the evolving features of FANS, but initially posed significant diagnostic challenges due to the rarity of this entity.

Key imaging findings included multiple scattered foci of abnormal T2/FLAIR hyperintensity and enhancement throughout the brain, progressing to numerous ring-enhancing lesions with associated calcifications. Late-stage imaging showed large destructive lesions with significant mass effect, including a 3.6 cm rim-enhancing lesion causing 1.2 cm midline shift and ventricular entrapment.

Early radiological differentials included infection, neurological manifestations of chronic graft-versus-host disease, cerebrovascular disease, and even aggressive brain tumors.

Biopsy revealed necro-inflammation, with tumor analysis identifying a significant ESR1/CCDC170 gene variant. The clinical course was marked by relentless progression including cognitive decline, weakness, imbalance, and seizures. Multiple immunosuppressive therapies were attempted with limited success.

This case emphasizes the importance of recognizing FANS imaging patterns, which progress from small enhancing lesions to large, destructive ones. The distinctive imaging features, combined with a history of Fanconi anemia, should prompt consideration of FANS in the differential diagnosis, even when other causes may seem more likely.

Awareness of FANS as a complication in Fanconi anemia patients is crucial for timely diagnosis and management. Emphasis needs to be placed on researching effective treatments, as current options have limited success in halting progression. Recognizing FANS is essential to prevent unnecessary and harmful treatments for misdiagnosed conditions. Read More

Authors:  Martinez-sicari Jorge , Shahid Mehreen , Mahdi Eman , Canissario Ryan , Richard Hope , Sisler India , Jones Kathryn , Mishra Chakradhar , Vorona Gregory

Keywords:  Genetics, Brain, Inflammation

Dicamillo Paul,  Berlin Sheila,  Vasavada Pauravi

Final Pr. ID: Poster #: CR-010

Generalized arterial calcification of infancy (GACI) is a rare, often fatal disease due to cardiovascular sequellae (cyanosis, respiratory distress, hypertension and cardiomegaly) from widespread arterial calcification and/or narrowing of medium and large diameter vessels. Other findings can include periarticular calcification, pseudoxanthoma elasticum, hearing loss, intestinal ischemia, rickets and hypo/hyperphasphatemia. A database of worldwide cases implicates genes ENPP1 and ABCC6.

Our patient presented late in gestation. Although a 20 week fetal ultrasound was unremarkable, a 36 week ultrasound showed polyhydramnios, moderate pericardial effusion and moderate to severe tricuspid regurgitation; these findings prompted a C-section delivery. Early in his course, the patient developed biventricular dysfunction, systemic and pulmonary hypertension and respiratory failure requiring mechanical ventillation. Splenic calcifications, left pelvicaiectasis and lenticulostriate vasculopathy was documented in first week of life. The thoracic aorta, pulmonary artery and coronary artery were echogenic and thickened. Etidronate therapy, a treatment used for the first months to years of life to block bone mineralization until the arterial calcifications resolve, was started within 24 hours of life. However, this therapy can and did result in the development of rickets. Genetic testing revealed two mutations in the ABCC6 gene as can be seen in early onset GACI, a subtype with risk of pseudoxanthoma elasticum; our patient did exhibit hypermobile lower extremity joints. The patient's hypertension was eventually controlled with Amlodipine. Bulging fontenelles developed, likely due to ricket-impared skull growth. Calcification/narrowing of the bilateral carotids was seen. Additional complications included chronic pulmonary disease shown to be combination of chronic aspiration, nonspecific interstitial pneumonia and mild pulmonary arterial hypertensive changes. Rickets-related rib fractures further complicated the lung disease. Failure to thrive resulted in enteric feeding. Because of the severity of our patient's disease in which 6 month mortality can be as high as 85%, the treatment has aimed to prevent progression. Significant reduction in the arterial calcium burden has not yet been achieved, however the patient survived one year of treatment. Read More

Authors:  Dicamillo Paul , Berlin Sheila , Vasavada Pauravi

Keywords:  genetics, diphosphonate, hypertension

Raju Rajiv,  Quijano Carla,  Prada Carlos

Final Pr. ID: Poster #: SCI-032

Hemihyperplasia is most classically associated with Beckwidth Wiedemann, though there are many cases which are associated with other syndromes or are idiopathic in nature. Current screening recommendations for hemihyperplasia do not distinguish between different subtypes of hemihyperplasia. The purpose of this study was to determine whether there is a statistically significant difference in incidence of development of abdominal tumors between hemihyperplasia patients with Beckwidth Wiedemann Syndrome and Non Beckwidth Wiedemann associated hemihyperplasia. Read More

Authors:  Raju Rajiv , Quijano Carla , Prada Carlos

Keywords:  Beckwidth Wiedemann Syndrome, Hemihyperplasia, Genetics

Yadav Ratan,  Subramanian Subramanian

Final Pr. ID: Poster #: CR-041

Leigh disease is a mitochondrial encephalopathy characterized by bilateral symmetric involvement of the brainstem and basal ganglia. SURF1 variants demonstrate restricted diffusion and symmetric T2/FLAIR hyperintensity of the substantia nigra, periaqueductal gray, and inferior olivary nuclei. MORC2 mutations, though primarily affecting the peripheral nervous system (causing Charcot–Marie–Tooth disease, spinal muscular atrophy–like features, and DIGFAN syndrome), can present with Leigh-like MRI patterns, leading to diagnostic uncertainty. Distinguishing these entities on MRI is essential for targeted genetic testing and counseling.
The purpose of this study is to compare MRI findings of a child with a confirmed MORC2 mutation to those of SURF1-variant Leigh disease, highlighting overlapping and distinguishing brainstem features that aid differential diagnosis. Read More

Authors:  Yadav Ratan , Subramanian Subramanian

Keywords:  Genetics, MRI Brain, Mitochondrial Disease

Molto Garcia Jose Francisco,  Tochen Laura,  Rhee Jullie

Final Pr. ID: Poster #: EDU-087

Neurodegeneration with Brain Iron Accumulation comprises a clinically and genetically heterogeneous group of disorders that share the feature of high levels of iron in the basal ganglia. Although very rare, these disorders may be suspected commonly by radiologists when iron deposits in the basal ganglia are encountered. Generally, radiologists are not familiar with the MR phenotypes of these disorders beyond the typical ‘eye of the tiger’, which may lead to overcalling since nonspecific iron deposits in the basal ganglia are way more common than NBIA. The aim of this educational poster is to discuss the MR phenotypes of the four most common NBIA disorders to include BPAN, PKAN, PLAN and MPAN, comprising about 95% of the cases. We will not only review the typical auntminnie presentation but also, we will describe the earliest signs, such as the T2 hyperintense streak along the medial border of the pallidi of PKAN, interestingly before any iron deposition is evident. When available, we will discuss the follow-up cases to see how the patterns evolve over time. Finally, we will briefly review the anatomy of the basal ganglia, subthalamic nuclei, substantia nigra and their connections since it is of the utmost importance for the pattern recognition. We hope that this review helps radiologists recognize the NBIA phenotypes to be more confident in their differentials. Read More

Authors:  Molto Garcia Jose Francisco , Tochen Laura , Rhee Jullie

Keywords:  MR, Genetics, Iron

De Leon-benedetti Laura,  Martinez-rios Claudia,  Tierradentro-garcia Luis,  Kilicarslan Ozge,  Caro Domínguez Pablo,  Otero Hansel

Final Pr. ID: Poster #: EDU-079

PTEN-related hamartoma tumor syndromes (PHTS) arise from germline pathogenic variants in the Phosphatase and Tensin homolog (PTEN) gene and include a broad spectrum of autosomal dominant clinical phenotypes with overlapping features. Its diagnosis is made through genetic testing prompted by family history or clinical features. In pediatric patients the most common feature leading to genetic testing is macrocephaly, in combination with other clinical findings, presenting in early childhood.

PHTS is a multisystem disorder. Imaging findings on pediatric patients have a wide variability, but benign findings are the most common.
In this educational exhibit, we will summarize the imaging findings of pediatric patients with confirmed PTEN diagnosis, based on our experience from three large children’s hospitals.

The most common findings will be described by anatomical regions:
- Central nervous system: white matter lesions, prominence of perivascular spaces, prominence of the ventricles and extra-axial spaces, and a dysplastic gangliocytoma of the cerebellum.
- Thyroid/neck: benign lesions such as nodular goiter, follicular adenomas, colloid cysts, and features of thyroiditis and pediatric thyroid carcinoma.
- Chest/mediastinum: infrequent lesions such as sclerosing pneumocytoma or chest wall lesions.
- Nonvascular soft tissue masses: variable types of hamartomas including polyps, fibromas, and lipomas.
- Vascular soft tissue masses: hemangiomas and classic PTEN hamartoma of the soft tissues (PHOST).

At the end of our exhibit, we will include current suggested surveillance imaging protocol for these patients. Read More

Authors:  De Leon-benedetti Laura , Martinez-rios Claudia , Tierradentro-garcia Luis , Kilicarslan Ozge , Caro Domínguez Pablo , Otero Hansel

Keywords:  Radiology, Genetics, Pediatrics

Errampalli Eric,  Kosaraju Sriya,  Illimoottil Mathew,  Mcgowan Bryanna,  Boyd Alec,  Allam Emad

Final Pr. ID: Poster #: CR-026

Nail-patella syndrome (NPS) is a multisystemic autosomal dominant disease with neurologic, ocular, renal, and musculoskeletal manifestations. The incidence of NPS is reportedly 1 in 50,000, although this may be an underestimate due to its phenotypic variability allowing this disease to remain undiagnosed for multiple generations. A loss of function mutation of the LMXB1 gene, which influences dopaminergic and serotonergic neuronal differentiation, periocular mesenchymal development, renal podocyte development, limb patterning, and skull patterning, leads to NPS. Clinical findings include open-angle glaucoma, ocular hypertension, neuropathic pain and numbness/tingling, and renal failure. Absent, hypoplastic, or dystrophic fingernails are noted in 98% of cases. Almost all patients present with absent, hypoplastic, or irregular patellae that frequently sublux. About 70% of patients present with pathognomic iliac horns, which are corticomedullary processes continuous with the iliac bones at the gluteus medius muscle origin. Loss of skin creases over the distal interphalangeal joints is also a sensitive finding for NPS. Decreased extremity muscle mass and bone formation can lead to limited knee and elbow joint range of motion.

The subject of this case report is a 20-year-old female who presented to nephrology clinic for proteinuria. Onychia was noted on physical exam. Past medical history was significant for spastic diplegia, and surgical history included epiphysiodesis due to leg length discrepancy. The patient was relatively asymptomatic otherwise. CT of the pelvis demonstrated bilateral osseous excrescences of the iliac bones. Absence of the patella and posterior subluxation of the radial head were noted on radiographs. CT of the abdomen showed bilateral renal atrophy. Subsequent renal biopsy demonstrated findings consistent with NPS. The patient was placed on hemodialysis after progressing to renal failure.

The prognosis of NPS is favorable with proper screening precautions and early intervention; however, complications of this disease can lead to poor outcomes. Imaging is critical in diagnosing NPS through its musculoskeletal findings on radiography. Characteristic findings include small or absent patella, pathognomic bilateral iliac horns, abnormalities of the femoral condyles and trochlea, and radial head dysplasia/subluxation. Read More

Authors:  Errampalli Eric , Kosaraju Sriya , Illimoottil Mathew , Mcgowan Bryanna , Boyd Alec , Allam Emad

Keywords:  Nail-Patella Syndrome, Genetics, Multi-System

Chen Danling,  Kuehne Alexander,  Hwang James,  Benyakoub Amine,  Ehrlich Lauren,  Lisse Sean

Final Pr. ID: Poster #: CR-047

Pallister-Hall syndrome is an exceedingly rare genetic disorder characterized by multiorgan anomalies encompassing hypothalamic hamartoma, postaxial polydactyly, bifid epiglottis, renal malformations and imperforate anus. The syndrome arises from a mutation in the GLI3 gene, which can be inherited in autosomal dominant fashion or occur de novo. A significant manifestation of Pallister-Hall syndrome is the presence of a hypothalamic hamartoma, a benign tumor of the hypothalamus. Although benign, these lesions can cause severe endocrine dysfunction by interfering with the hypothalamic-pituitary axis. Abnormal neural or glial cell migration in the tuber cinereum of the hypothalamus leads to abnormal expansion of the hypothalamus, manifesting in a spectrum of pituitary dysfunction ranging from pituitary displacement to severe pan-hypopituitarism. A well-established feature of the hypothalamic hamartomas associated with Pallister-Hall syndrome is the incidence of gelastic seizures (so-called “laughing” seizures), characterized by episodes of involuntary laughing.

A male neonate was born with polydactyly, bifid epiglottis, cryptorchidism, and Hirschsprung’s disease. The patient was additionally found to have right sided vesicouteral reflux requiring extravesical ureteral reimplantation. Genetic analysis revealed a mutation in the GLI3 gene, compatible with Pallister-Hall syndrome. Once diagnosed, the patient underwent contrast-enhanced MR imaging of the brain which demonstrated a large lobulated 2.6 x 2.0 cm suprasellar mass with encroachment posteriorly upon the midbrain and associated superior displacement of the third ventricle. The lesion showed low-grade enhancement following gadolinium contrast administration, displayed no significant abnormality on diffusion-weighted or susceptibility weighted imaging, and was isodense to brain tissue on all sequences. Serial follow-up MRIs demonstrated minimal increase in size of the non-enhancing suprasellar mass. Findings were suggestive of hypothalamic hamartoma, in keeping with the classical presentation of Pallister-Hall syndrome. Read More

Authors:  Chen Danling , Kuehne Alexander , Hwang James , Benyakoub Amine , Ehrlich Lauren , Lisse Sean

Keywords:  Pituitary Abnormalities, Genetics, Genitourinary

El-hayani Reem,  Malik Ammara,  Manickam Sivakumar

Final Pr. ID: Poster #: CR-023

Introduction:
Smith-Lemli-Opitz syndrome (SLOS) is a rare autosomal recessive metabolic disorder caused by deficiency of 7-dehydrocholesterol reductase, leading to impaired cholesterol biosynthesis (Kelley & Hennekam, 2000). It has associations with multiple congenital anomalies, including craniofacial, cardiac, and genitourinary malformations. Renal abnormalities, including renal agenesis, affect around 25% of individuals with SLOS (Nowaczyk, 2020), yet little literature is available on how this manifests clinically.

Case:
We report a 6-month-old infant with a background of known SLOS admitted with vomiting, fever, and persistent electrolyte derangements despite IV fluids. Initial ultrasound of the urinary tract demonstrated increased echogenicity and moderate pelvicalyceal dilatation of the right kidney with mild ureteric dilatation. The left kidney was not visualised in the renal fossa, and a small elongated echogenic structure adjacent to the spleen was suggestive of an atrophic kidney. Follow-up ultrasound at 7 months confirmed absence of the left kidney, with compensatory hypertrophy of the right kidney and mild hydronephrosis. Serial chest radiographs revealed concurrent cardiomegaly and recurrent respiratory infections. The case was discussed in a multidisciplinary setting, and urology input confirmed the diagnosis of unilateral renal agenesis in the context of SLOS.

Discussion:
While renal anomalies such as hypoplasia, duplication, and vesicoureteric reflux have been reported in SLOS (Nowaczyk & Irons, 2012), more data is needed to explore how this may clinically present. This case highlights the importance of systematic renal evaluation in children with SLOS, particularly when presenting with acute kidney injury or electrolyte imbalance (Porter, 2008) as a result of unilateral or bilateral kidney agenesis. This report builds the case for early urological screening of all children with SLOS, allowing for early detection and longitudinal monitoring, which is essential for guiding management, anticipating complications, and counselling families.

References:
Kelley RI, Hennekam RC. Smith-Lemli-Opitz syndrome. J Med Genet. 2000;37(5):321–335.
Nowaczyk MJ, Wassif CA. Smith-Lemli-Opitz Syndrome. In: Adam MP, Feldman J, Mirzaa GM, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1998
Nowaczyk MJ, Irons MB. Smith-Lemli-Opitz syndrome: phenotype, natural history, and epidemiology. Am J Med Genet C Semin Med Genet. 2012 Read More

Authors:  El-hayani Reem , Malik Ammara , Manickam Sivakumar

Keywords:  Kidneys, Genetics, Genitourinary

Mistry Mikesh,  Dickinson Fiona,  Shenoy Savitha

Final Pr. ID: Poster #: CR-017

DSD encompasses a wide range of conditions presenting in newborns or adolescents. The clinical features usually involve atypical genitalia in infancy or atypical pubertal development in adolescence. Those assigned female sex and later identified to have 46XY DSD pose extremely challenging and sensitive presentation to families and professionals. The assessment requires consideration of sexual identity issues among adolescents and potential for future adult sexual functioning and fertility. Radiological assessment (ultrasound and MRI) in the evaluation of these cases is paramount in providing information on the location and state of the gonads and Mullerian structures.

We report a selection of cases demonstrating the role of imaging in children and adolescents with a female phenotype and assigned female sex at birth but later identified to have 46XY DSD.

A 3 month old female presented with ambiguous genitalia and karyotyping confirmed 46XY. Ultrasound demonstrated left hydronephrosis and a bicornuate uterus with no ovarian or testicular tissue identified. MRI confirmed left hydronephrosis secondary to pelviureteric junction obstruction and a didelphys uterus with absence of ovarian and testicular tissue. Genetic tests confirmed MYRF-related cardiac urogenital syndrome and the parents opted to raise the child as female and with an early gonadectomy planned.

A 14 year old girl presented with primary amenorrhoea and deepening voice. She was noted to have 5cm phallus-like structure, unfused labioscrotal folds and a single genital orifice. Karyotyping confirmed 46XY and ultrasound demonstrated no ovarian or uterine tissue. MRI revealed bilateral testes in the inguinal canals, seminal vesicles that connected with a vaginal cavity and a small penile shaft. Genetic tests confirmed 5α-reductase deficiency and a puberty blocker was offered to allow the patient to explore her gender identity.

A 16 year old female presented with primary amenorrhoea, but had normal female external genitals and pubertal breast changes. Karyotyping confirmed 46XY and ultrasound demonstrated no ovarian, uterine or testicular tissue. Genetic tests confirmed complete androgen insensitivity and the patient opted to continue female identity and undergo gonadectomy in the future.

These cases demonstrate the vital role of imaging modalities in the evaluation of DSD by providing significant and crucial information, which is paramount in the diagnosis and ongoing management for these patients. Read More

Authors:  Mistry Mikesh , Dickinson Fiona , Shenoy Savitha

Keywords:  Paediatric Radiology, Genetics

Kelly Anna,  Huang Jessie,  Carlock Hunter,  Chaturvedi Apeksha

Final Pr. ID: Poster #: EDU-005

Somatic overgrowth syndromes and their underlying genetic causes are an emerging area of research and treatment. The PI3K/AKT/mTOR signaling pathway is essential for regulating normal cell growth and division, disruption of which can lead to a diverse array of overlapping disease states including a spectrum of somatic overgrowth disorders.

The goal of this exhibit is to familiarize radiologists with the clinical and imaging manifestations of disease states resulting from the above genetic aberration. We first review the physiology of the PI3K/AKT/mTOR signaling pathway and the mechanisms by which its disruption can lead to disease. We then discuss the spectrum of pathology which can result from such a disruption. We overview the genetic aspects of the disease, focusing on overgrowth syndromes including fibroadipose vascular anomaly (FAVA), Parkes Weber, Klippel-Trenaunay, CLOVES syndrome, and PTEN hamartoma tumor syndrome. We then present imaging findings for each of these syndromes using cases encountered at our own institution. Radiologists familiar with clinical-radiologic findings of these entities can direct patients to appropriate genetic testing, thereby guiding decisions regarding endovascular therapy, surgery, and recently available oral medications. Read More

Authors:  Kelly Anna , Huang Jessie , Carlock Hunter , Chaturvedi Apeksha

Keywords:  Genetics

Vázquez Elida,  Delgado Ignacio,  Sanchez-montañez Angel,  Escudero Jose,  Gómez David,  Riera Luis

Final Pr. ID: Poster #: EDU-027

Tubulins are a component of microtubules, which are critical to the processes of mitosis, axon navigation, and neuron migration, all key factors in brain development. Mutations in tubulin genes can alter the normal function and structure of microtubules, leading to complex disorders of brain development and brain malformations. Disorders of microtubules formation affect multiple aspects of brain development, resulting in multiple malformations that can be recognized on cranial MRI. A significant characteristic is the wide spectrum of severity, from severe forms often present at birth to milder conditions, sometimes seen in asymptomatic parents of affected individuals.
The purpose of this educational poster is to present the main postnatal and prenatal MRI patterns that can help to suspect a tubulinopathy and guide subsequent genetic testing for confirmation. Read More

Authors:  Vázquez Elida , Delgado Ignacio , Sanchez-montañez Angel , Escudero Jose , Gómez David , Riera Luis

Keywords:  Fetal Brain MRI, Genetics, Central Nervous System

Law Emily,  Sarma Asha,  Crane Gabriella,  Luo Yu

Final Pr. ID: Poster #: CR-030

Trichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant skeletal dysplasia characterized by distinctive craniofacial (pear-shaped nose, long philtrum, thin upper lip, prominent ears, sparse, slow-growing hair, and dystrophic nails) and skeletal abnormalities (short stature, brachydactyly, cone-shaped epiphyses, and hip dysplasia). When bilateral Legg-Calvé-Perthes disease (LCPD) occurs, the femoral head changes typically manifest symmetrically and simultaneously, often suggesting an underlying skeletal dysplasia. We present an unusual case of an 11-year-old male with bilateral asymmetric “Perthes disease,” with the left hip in the late or healing phase and the right hip in the early phase. The patient had no prior history or treatment for left-sided LCPD. He underwent right hip core decompression before genetic consultation. On physical examination, he exhibited relatively sparse hair, short stature, a pear-shaped nose with underdeveloped alae, and shortened digits. Recognition of these characteristic craniofacial features prompted the geneticist to order a skeletal survey and TRPS1 panel. Skeletal survey demonstrated bilateral symmetric cone-shaped epiphyses in the proximal phalanges of both feet and the middle and distal phalanges of the hands, coxa magna and breva of the left hip, and flattening and sclerosis of the right proximal femoral epiphysis. Additional findings included tonguing of multiple thoracic vertebrae, short pedicles of the lower lumbar spine, and decreased interpedicular distance at L5. Differential diagnoses include TRPS, pseudoachondroplasia, multiple epiphyseal dysplasia, or spondyloepiphyseal dysplasia. Molecular testing identified a heterozygous pathogenic variant in TRPS1 (c.1630C>T, p.Arg544*), confirming the diagnosis of TRPS I. This case illustrates that temporally asymmetric, bilateral Perthes-like changes may obscure an underlying skeletal dysplasia and the importance of recognizing characteristic craniofacial features to guide timely genetic evaluation and management. Read More

Authors:  Law Emily , Sarma Asha , Crane Gabriella , Luo Yu

Keywords:  Skeletal, Genetics, Dysplasia

Hwang James,  Chen Danling,  Kuehne Alexander,  Benyakoub Amine,  Tu Long,  Lisse Sean,  Ehrlich Lauren

Final Pr. ID: Poster #: CR-061

Filamin A (FLNA) is a widely expressed X-linked dominant gene that encodes Filamin A, a protein that crosslinks actin filaments and plays a crucial role in the structure of the cell cytoskeleton. With such a broad role, FLNA mutations are especially consequential and can result in cardiovascular malformations, intellectual disability, skeletal dysplasia, and neuronal migration abnormalities. Additionally, recent literature has linked FLNA mutation to pediatric-onset interstitial lung disease.
A three-month-old female with a history of atrial septal defect, patent ductus arteriosus, pulmonary valve dysplasia, micrognathia, and recent hospitalization for parainfluenza infection causing respiratory failure presented to the emergency department with worsening hypoxemia and respiratory distress. Initial chest radiograph demonstrated an interval increase in bilateral patchy opacifications suggestive of worsening multifocal infection. The patient was subsequently admitted. The patient’s clinical status failed to improve after multiple days of admission. A non-contrast CT study of the chest revealed multiple regions of air trapping, atelectasis, coarsened interstitial markings, and diffuse septal thickening, differential diagnosis included interstitial lung disease versus congenital alveolar abnormality. Of note, MR imaging of the brain obtained showed diffuse nodularity along the subependymal lining of the lateral ventricles and temporal horns, compatible with gray matter heterotopia. This prompted genetic testing which revealed Filamin A deficiency.
Filamin A mutation typically presents radiographically with hyperinflation of the lungs with scattered atelectasis, which can be complicated by concomitant pneumonia. This appearance can mimic pulmonary emphysema and bronchopulmonary dysplasia. Cardiac anomalies are a common manifestation of the mutation; notably, our patient had a history of a dysplastic pulmonary valve, ASD and PDA. CT imaging patterns vary and can present as a combination of cystic and diffuse ground-glass changes, hyperinflation, and emphysema. After extensive consultation, our patient transitioned to palliative care and ultimately passed away at 5 months of age. Maintaining a high index of suspicion for this rare but important entity is crucial to accurately diagnosing this inherited mutation, treating affected patients appropriately, and providing patients and their families with essential information regarding prognosis and inheritance patterns. Read More

Authors:  Hwang James , Chen Danling , Kuehne Alexander , Benyakoub Amine , Tu Long , Lisse Sean , Ehrlich Lauren

Keywords:  Interstitial Lung Disease, Genetics, Chest Computed Tomography (CT)