1a Answer A. There is an enhancing mass at the optic pathway and hypothalamic region consistent with glioma. There is also an enhancing exophytic mass arising from the right dorsolateral aspect of the medulla also consistent with glioma. Neurofibromatosis (NF) type 1 (NF1) is a disease characterized by the growth of noncancerous tumors called neurofibromas. These are located on or just underneath the skin, as well as in the brain and peripheral nervous system. They may also form in other body parts, including the eye and orbit.

Ophthalmologic manifestations of NF-1 include the following:

An estimated 15% to 40% of children with NF1 have optic nerve glioma or visual pathway gliomas involving the optic nerve, chiasm, or optic tract. Some of these lesions are asymptomatic. Bilateral optic nerve gliomas are almost pathognomonic for NF1. Optic nerve gliomas are locally invasive and slow growing with low malignant potential. However, chiasmatic gliomas may invade the hypothalamus and third ventricle, causing obstructive hydrocephalus.

Reference: Listernick R, Charrow J, Greenwald MJ, Esterly NB. Optic gliomas in children with neurofibromatosis type 1. J Pediatr 1989;114(5):788-792.

1b Answer B. Café au lait spot. Flat pigmented lesions of the skin called café au lait spots are hyperpigmented lesions that may vary in color from light brown to dark brown; this is reflected by the name of the condition, which means “coffee with milk.” The borders may be smooth or irregular. These spots can grow from birth and can continue to grow throughout the person’s lifetime. Having six or more café au lait spots > 5 mm in diameter before puberty, or > 15 mm in diameter after puberty, is a diagnostic feature of neurofibromatosis type I, but other features are required to diagnose NF-1.

A port-wine stain (nevus flammeus), also commonly called a firemark, is almost always a birthmark; in rare cases, it can develop in early childhood. It is caused by a vascular anomaly (a capillary malformation in the skin). Port-wine stains are named for their coloration, which is similar in color to port-wine, a fortified red wine from Portugal. Port-wine stains may be part of a syndrome such as Sturge-Weber syndrome or Klippel-Trénaunay-Weber syndrome.

Facial angiofibromas (adenoma sebaceum) is a rash of reddish spots or bumps, which appears on the nose and cheeks in a butterfly distribution. They consist of blood vessels and fibrous tissue. Facial angiofibromas are one of the classic dermatological findings of tuberous sclerosis.

Ataxia telangiectasia can cause features of early aging such as premature graying of the hair. It can also cause vitiligo (an autoimmune disease causing loss of skin pigment resulting in a blotchy “bleach-splashed” look) and warts, which can be extensive and recalcitrant to treatment.

References: Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006;355(13):1345-1356.

Nowak CB. The phakomatoses: dermatologic clues to neurologic anomalies. Semin Pediatr Neurol 2007;14(3):140-149.

2a Answer C. CT demonstrates pial and leptomeningeal vascular calcifications with a small left cerebral hemisphere and distortion of the left lateral ventricle. MRI redemonstrates postsurgical changes of left-sided craniotomy and hemispherectomy. There is left cerebral atrophy and gyriform susceptibility along the residual left cerebral hemisphere. Sturge-Weber syndrome, or encephalotrigeminal angiomatosis, is a phakomatosis characterized by facial port-wine stains and pial angiomas. The diagnosis is usually suspected with the presence of congenital facial cutaneous hemangioma (also known as port-wine stain or facial nevus flammeus). This feature is almost always present and usually involves the ophthalmic division (V1) of the trigeminal nerve. If the V1 territory of the trigeminal nerve is not involved, Sturge-Weber syndrome is unlikely. The differential is a combination of that for multiple intracranial calcifications, cerebral hemiatrophy, and leptomeningeal enhancement, and therefore includes the following:

References: Comi AM. Update on Sturge-Weber syndrome: diagnosis, treatment, quantitative measures, and controversies. Lymphat Res Biol 2007;5(4):257-264.

Griffiths PD. Sturge-Weber syndrome revisited: the role of neuroradiology. Neuropediatrics 1996;27(06):284-294.

2b Answer A. Port-wine stain. A port-wine stain (nevus flammeus), also commonly called a firemark, is almost always a birthmark; in rare cases, it can develop in early childhood. It is caused by a vascular anomaly (a capillary malformation in the skin). Port-wine stains are named for their coloration, which is similar in color to port-wine, a fortified red wine from Portugal. Port-wine stains may be part of a syndrome such as Sturge-Weber syndrome or Klippel-Trénaunay-Weber syndrome.

Flat pigmented lesions of the skin called café au lait spots are hyperpigmented lesions that may vary in color from light brown to dark brown; this is reflected by the name of the condition, which means “coffee with milk.” The borders may be smooth or irregular. These spots can grow from birth and can continue to grow throughout the person’s lifetime. Having six or more café au lait spots > 5 mm in diameter before puberty, or > 15 mm in diameter after puberty, is a diagnostic feature of neurofibromatosis type I, but other features are required to diagnose NF-1.

Facial angiofibromas (adenoma sebaceum) is a rash of reddish spots or bumps, which appears on the nose and cheeks in a butterfly distribution. They consist of blood vessels and fibrous tissue. Facial angiofibromas are one of the classic dermatological findings of tuberous sclerosis.

Ataxia telangiectasia can cause features of early aging such as premature graying of the hair. It can also cause vitiligo (an autoimmune disease causing loss of skin pigment resulting in a blotchy “bleach-splashed” look) and warts, which can be extensive and recalcitrant to treatment.

References: Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med 2006;355(13):1345-1356.

Nowak CB. The phakomatoses: dermatologic clues to neurologic anomalies. Semin Pediatr Neurol 2007;14(3):140-149.

3a Answer D. The abdominal radiograph demonstrates two lucent regions in the upper abdomen (double bubble) consistent with duodenal atresia in the setting of trisomy 21. The two bubbles represent the stomach lumen and the duodenal bulb, respectively. Down syndrome (or trisomy 21) is the most common trisomy and also the commonest chromosomal disorder. It is a major cause of intellectual disability and also has numerous multisystem manifestations.

Antenatal “soft markers” for aneuploidy include

Structural abnormalities include

Reference: Smith-Bindman R, Hosmer W, Feldstein VA, et al. Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis. JAMA 2001;285(8):1044-1055.

3b Answer C. Trisomy 21. Aneuploidy refers to an abnormal number of chromosomes and is a type of chromosomal abnormality. There are large number potential aneuploidic anomalies. The most common three aneuploidies encountered in the obstetric and pediatric population include trisomy 21 (most common), trisomy 18, and trisomy 13. The double bubble demonstrated on the abdominal radiograph is most consistent with duodenal atresia in the setting of trisomy 21. Trisomy 13 also called Patau syndrome presents with heart defect, brain or spinal cord abnormalities, microphthalmia, polydactyly, cleft lip/palate, and hypotonia. Trisomy 18 also called Edwards syndrome present with intrauterine growth restriction, low birth weight, heart defects, abnormal head shape, micrognathia, and clenched fists with overlapping fingers. Trisomy 23 is also known as XXY male syndrome, and Klinefelter syndrome is associated with male infertility, gynecomastia, small testes, and reduced facial and body hair.

Reference: Estroff JA. Imaging clues in the prenatal diagnosis of syndromes and aneuploidy. Pediatr Radiol 2012;42(Suppl 1):5-23. https://doi.org/10.1007/s00247-011-2264-3

4 Answer B. There is bilateral microphthalmia and retro-ocular cyst-like structures consistent with coloboma. The bilateral olfactory apparatus are absent. CHARGE syndrome is an acronym that classically describes a combination of head and neck, cardiac, CNS, and genitourinary disorders:

C: Coloboma

H: Heart defects (congenital heart disease)

A: Atresia (choanal)

R: Retardation (mental)

G: Genital hypoplasia

E: Ear abnormalities/deafness

Coloboma is collective term encompassing any focal discontinuity in the structure of the eye. Colobomas are due to failure of closure of the choroidal fissure posteriorly. Typically, colobomas are bilateral, small and are not accompanied by other deeper abnormalities. It occurs along the inferomedial aspect of the globe and optic nerve. On CT or MRI, the affected globe is usually small with a focal posterior defect in the globe with vitreous herniation. A retrobulbar fluid-density cyst may be present.

References: Simmons JD, LaMasters D, Char D. Computed tomography of ocular colobomas. AJR Am J Roentgenol 1983;141(6):1223-1226.

Tellier AL, Cormier-daire V, Abadie V, et al. CHARGE syndrome: report of 47 cases and review. Am J Med Genet 1998;76(5):402-409.

5a Answer B. CTA of the chest demonstrates a dilated aortic root/ascending aorta measuring up to 3.6 cm at the sinuses of Valsalva. Marfan syndrome is a multisystem connective tissue disease with autosomal dominant inheritance of defect in fibrillin 1 gene. The affected patients are tall with long disproportionate extremities, have pectus excavatum and arachnodactyly, and may also experience upward and lateral optic lens dislocation. Cardiovascular disease is common, particularly aortic root dilatation and dissection, which is the most common cause of sudden death in these patients.

Cardiovascular complications are predominantly due to cystic medial necrosis of the vessels and are the most frequent cause of death. Aortic root dilatation and myxomatous degeneration of the mitral valve resulting in mitral valve regurgitation are the most two common cardiac manifestations. Among the total number of patients with root aneurysms, those with a diagnosis of Marfan syndrome dominate the younger age range but they are nevertheless a minority of all patients with ascending aortic aneurysm. They are prone to acute dissection, and prior to the introduction of prophylactic root replacement, this was the cause of death in twothirds of all patients and often at a young age.

References: Ha HI, Seo JB, Lee SH, et al. Imaging of Marfan syndrome: multisystemic manifestations. Radiographics 2007;27(4):989-1004.

Treasure T, Takkenberg JJM, Pepper J. Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms. Heart 2014;100(20):1571-1576. doi:10.1136/heartjnl-2013-305132.

5b Answer C. 45 mm. Current guidelines for the management of valvular heart disease state that irrespective of the presence and severity of aortic valve regurgitation, surgery should be considered in patients with Marfan syndrome with risk factors (family history of dissection, size increase 2 mm/year in repeated examinations) who have aortic root disease with a maximum ascending aortic diameter of ≥45 mm.

Reference: Treasure T, Takkenberg JJ, Pepper J. Surgical management of aortic root disease in Marfan syndrome and other congenital disorders associated with aortic root aneurysms. Heart 2014;100(20)1571-1576. doi:10.1136/heartjnl-2013-305132.

6a Answer D. US demonstrates a mixed solid-cystic mass in the upper left kidney. MRI demonstrates an enlarged left kidney containing a collection of multiple cysts within the medulla of the upper pole, as well as multiple peripheral subcortical cysts. Left nephrectomy was performed, and pathology demonstrated a focus of Wilms tumor present in a background of nephroblastomatosis. Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder. The syndrome is characterized by omphalocele, macroglossia, gigantism, neonatal hypoglycemia, hemihypertrophy, hepatosplenomegaly, nephromegaly, cardiac anomalies, adrenal cytomegaly, pancreatic islet cell hyperplasia, facial nevus flammeus, and ear lobe creases. There is a high risk (about 10%) of development of embryonal neoplasms, particularly Wilms tumor in the child with BWS, especially those with hemihypertrophy.

References: Andrews MW, Amparo EG. Wilms’ tumor in a patient with Beckwith-Wiedemann syndrome: onset detected with 3-month serial sonography. AJR Am J Roentgenol 1993;160(1):139-140.

Choyke PL, Siegel MJ, Oz O, et al. Nonmalignant renal disease in pediatric patients with Beckwith-Wiedemann syndrome. AJR Am J Roentgenol 1998;171(3):733-737.

6b Answer C. Denys-Drash syndrome. The WT1-related Wilms tumor (WT) syndromes are a group of hereditary disorders caused by alterations in a gene known as WT1. This group of disorders includes:

Patients with Denys-Drash syndrome may develop the following clinical features:

In addition to the WT1-related Wilms tumor syndromes, there are a number of other genetic conditions associated with the development of WT. Some of these conditions include the following:

Patients with these conditions have a greater risk of developing a malignant tumor of the kidney known as Wilms tumor (WT) or nephroblastoma. Wilms tumor is the most common type of kidney cancer affecting children. Very rarely, WT can occur in adults.

Reference: Lowe LH, Isuani BH, Heller RM, et al. Pediatric renal masses: Wilms tumor and beyond. Radiographics 2000;20(6):1585-1603.

7a Answer B. US demonstrates an echogenic soft tissue mass at the posterior neck. MR was performed to assess for pulmonary lymphangiectasia in the setting of genetically proven Turner syndrome. The cystic hygroma is demonstrated (white arrows).

Cystic hygromas can occur as an isolated finding or in association with other birth defect as part of a syndrome. They result from environmental factors, genetic factors, or unknown factors.

Environmental causes for cystic hygroma include

Genetic syndromes with cystic hygroma as a clinical feature:

The pattern of inheritance for these syndromes varies depending upon the specific syndrome. Isolated cystic hygroma can be inherited as an autosomal recessive disorder for which parents are “silent” carriers. Finally, a cystic hygroma can occur from an unknown cause.

Other imaging findings in Turner syndrome include

Reference: Chen C-P, Chien S-C. Prenatal sonographic features of Turner syndrome. J Med Ultrasound 2007;15:251-257.

7b Answer B. 11 to 13 weeks. A nuchal translucency scan (also called first trimester of pregnancy screening) is carried out during weeks 11 to 13 of a pregnancy. The scan uses ultrasound to screen for Down syndrome or other chromosomal or inherited conditions in the fetus. Other nonchromosomal conditions, such as neural tube defects, abdominal wall defects, limb abnormalities, and some congenital heart disease, can also be detected at this stage of the pregnancy.

Screening can determine the likelihood of risk of an abnormality but does not diagnose the condition. If screening does identify a possible risk, it does not necessarily mean there is an abnormality present but does mean that further testing is necessary. A nuchal translucency scan is combined with the mother’s age and results of a blood test showing the mother’s pregnancy hormone levels to provide a “combined risk.”

Without the blood test, screening is 75% accurate for predicting Down syndrome. With the blood test, the accuracy increases to 85%. Women who return a high-risk result from the screening will be offered formal genetic testing using other procedures, such as amniocentesis or chorion villus sampling (CVS).

Reference: ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstetr Gynecol 2007;109(1):217-227.

8a Answer C. The right and left glenohumeral joints appear subluxed or dislocated. This patient with known Ehlers-Danlos syndrome (EDS) belongs to a group of collagen disorders or hereditary connective tissue disease. There are at least 10 subtypes with variable inheritance patterns. The majority are autosomal dominant. EDS clinically manifests by skin hyperelasticity and fragility, joint hypermobility, and blood vessel fragility with bleeding diathesis. Skeletal findings include hemarthrosis (especially knees), recurrent joint dislocation including spontaneous dislocation of the temporomandibular joint, precocious osteoarthritis, kyphoscoliosis, and spondylolisthesis.

Reference: Ayres JG, Pope FM, Reidy JF, et al. Abnormalities of the lungs and thoracic cage in the Ehlers-Danlos syndrome. Thorax 1985;40(4):300-305.

8b Answer B. Autosomal dominant.

9a Answer B. This patient was treated for tetralogy of Fallot, major aortopulmonary collateral arteries, and hypoplastic pulmonary arteries. A right ventricular outflow track transjugular patch was placed in addition to patch closure of an ASD and VSD. The 22q11.2 deletion syndrome, also known as the DiGeorge syndrome (DGS) or velocardiofacial syndrome, is a syndrome where a small portion of the chromosome 22 is lost and results in a variable but a recognizable pattern of physical and behavioral features. The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia. The most common cardiac defects account for two-thirds of the cardiac anomalies seen in patients with DGS and include the following:

References: Alikaşifoğlu M, Malkoç N, Ceviz N, et al. Microdeletion of 22q11 (CATCH 22) in children with conotruncal heart defect and extracardiac malformations. Turk J Pediatr 2000;42(3):215-218.

McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore) 2011;90:1-18.

9b Answer D. Chromosome 22 deletion.

10 Answer A. MRI demonstrates an extensive venous vascular malformation of the right lower extremity, which extends from the level of the groin to the distal tibiotalar joint and involves both the subcutaneous and intramuscular compartments. Klippel-Trenaunay syndrome (KTS) is a complex congenital disorder characterized by the classic triad of capillary malformation, venous malformation, and limb overgrowth, with or without lymphatic malformation. In KTS, the persistence of embryonic avalvular venous structures, most notably the lateral vein of the thigh (lateral marginal vein of Servelle) and sciatic vein, can result in dilated tortuous varicosities, with superficial ones being more often located over the anterolateral thigh and leg.

MRI with and without gadolinium contrast is the imaging study of choice to define the nature and extent of vascular anomalies in patients with KTS. MRI provides the highest diagnostic accuracy in the evaluation of the underlying venous and lymphatic abnormalities, as well as soft tissue and bony overgrowth. Venous malformations show uniform enhancement, whereas lymphatic malformations demonstrate rim or septal enhancement of cyst walls. Fluid-fluid levels and high T2 signal intensity are characteristic of lymphatic malformations. The presence of phleboliths as signal voids is characteristic of venous malformations.

Hemihypertrophy or hemihyperplasia describes an asymmetry in size between the right and left side of the body. This can arise sporadically as isolated hemihypertrophy or it can arise as part of a syndrome:

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder characterized by:

Maffucci syndrome is a congenital nonhereditary mesodermal dysplasia characterized by multiple enchondromas with soft tissue venous malformations (hemangiomas). On imaging, it is usually portrayed by a short limb with metaphyseal distortions because of multiple enchondromas, which may appear grotesque, and soft tissue masses with phleboliths depicting hemangiomas.

References: Flors L, et al. MR imaging of soft-tissue vascular malformations: diagnosis, classification, and therapy follow-up. Radiographics 2011;31:1321-1340; discussion: 1340-1341.

Roebuck DJ, Howlett DC, Frazer CK, et al. Pictorial review: the imaging features of lower limb Klippel-Trenaunay syndrome. Clin Radiol 1994;49(5):346-350.

11 Answer D. PET imaging demonstrates diffusely increased FDG uptake identified within the spleen, which is enlarged in size concerning for lymphomatous involvement. Multiple enlarged mesenteric and retroperitoneal lymph nodes are also present and demonstrate increased FDG uptake. Posttransplant lymphoproliferative disorders (PTLD) are lymphoid and/or plasmacytic proliferations that occur in the setting of solid organ or allogeneic hematopoietic cell transplantation as a result of immunosuppression. They are among the most serious and potentially fatal complications of transplantation. While the majority appear to be related to the presence of Epstein-Barr virus (EBV), EBV-negative disease does occur.

The range of appearances is large due to the number of possible sites. In general, extranodal involvement is three to four times more common than is nodal involvement and resembles primary lymphoma of those organs:

References: Pickhardt PJ, Siegel MJ, Hayashi RJ, et al. Posttransplantation lymphoproliferative disorder in children: clinical, histopathologic, and imaging features. Radiology 2000;217(1):16-25.

Meador TL, Krebs TL, Cheong JJ, et al. Imaging features of posttransplantation lymphoproliferative disorder in pancreas transplant recipients. AJR Am J Roentgenol 2000;174(1):121-124.

12 Answer A. Left hand radiograph demonstrates polydactyly of the first digit. MRI of the abdomen demonstrates bilateral dysplastic kidneys with multiple cysts, hydronephrosis, and an ectopically located left kidney. Spine radiograph and MRI demonstrate segmentation and fusion anomalies in the upper lumbar spine with associated kyphosis, unchanged.

VACTERL is an acronym that describes a nonrandom constellation of congenital anomalies. It is not a true syndrome as such and is equivalent to the VATER anomaly.

The acronym VACTERL derives from the following:

At least three of the above features (in each category) are considered necessary for the diagnosis of this condition.

Reference: Solomon BD, et al. An approach to the identification of anomalies and etiologies in neonates with identified or suspected VACTERL (vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, cardiac anomalies, renal anomalies, and limb anomalies) association. J Pediatr 2014;164:451-457.e1.