Novel in-frame FLNB deletion causes Larsen syndrome in a three-generation pedigree.

A 4-yr-old female with congenital knee dislocations and joint laxity was noted to have a strong maternal family history comprising multiple individuals with knee problems and clubfeet. As the knee issues were the predominant clinical features, clinical testing included sequencing of LMX1B, TBX2, and TBX4, which identified no significant variants. Research genome sequencing was performed in the proband, parents, and maternal grandfather. A heterozygous in-frame deletion in FLNB c. 5468_5470delAGG, which predicts p.(Glu1823del), segregated with the disease. The variant is rare in the gnomAD database, removes a residue that is evolutionarily conserved, and is predicted to alter protein length. Larsen syndrome may present with pathology that primarily involves one joint and thus may be difficult to differentiate clinically from other skeletal dysplasias or arthrogryposis syndromes. The p.(Glu1823del) variant maps to a filamin repeat domain where other disease-causing variants are clustered, consistent with a probable gain-of-function mechanism. It has reportedly been observed in two individuals in the gnomAD database, suggesting that mild presentations of Larsen syndrome, like the individual reported here, may be underdiagnosed in the general population.

Free-floating Paratesticular Calcifying Fibrous Pseudotumors in a Pediatric Patient.

Paratesticular masses are a relatively common finding in males. The majority are benign, as opposed to testis masses, which tend to be malignant. Fibrous pseudotumors are rare, but are the third most common paratesticular tumor after adenomatoid and lipoma. The exact cause is unclear but likely from a fibroinflammatory reaction. Because of the non-specific findings on physical exam and scrotal ultrasound, patients may undergo scrotal exploration and occasionally orchiectomy, in spite of the benign nature of this lesion. Here we report the rare case of free-floating paratesticular calcifying fibrous pseudotumors in a prepubertal patient.

Diffuse intestinal ganglioneuromatosis in a child.

A 7 year old male with a history of congenital neutropenia and growth hormone deficiency presented with abdominal pain, fevers, and diarrhea. Imaging and endoscopy revealed significant inflammation of the ascending colon with stenosis at the level of the hepatic flexure. A right hemicolectomy was performed, and pathologic findings were consistent with diffuse intestinal ganglioneuromatosis. Due to recurrent mass effect at the intestinal anastomotic site detected radiologically, a second intestinal resection was performed 7 months later. Genetic testing was negative for mutations in the RET protooncogene, NF1 and PTEN tumor suppressor genes. We report a case of diffuse intestinal ganglioneuromatosis in a child with congenital neutropenia.

Pulmonary hyalinizing granuloma and retroperitoneal fibrosis in an adolescent.

We describe a 15-year-old boy who developed pulmonary hyalinizing granuloma (PHG) and retroperitoneal fibrosis (RPF). His PHG and RPF were not associated with histoplasmosis or tuberculosis and appeared to represent idiopathic autoimmune phenomena. This is the first reported case of PHG in a pediatric patient and the fourth reported co-occurrence of PHG and RPF. The use of F-18 fluorodeoxyglucose positron emission tomography in the diagnostic and follow-up evaluation of PHG is reported.

Comparison of quiet breathing and controlled ventilation in the high-resolution CT assessment of airway disease in infants with cystic fibrosis.

BACKGROUND: Respiratory motion and low lung volumes limit the quality of HRCT examinations in infants and young children. OBJECTIVE: To assess the effects of respiratory motion and lung inflation on the ability to diagnose airway abnormalities and air trapping (AT) using HRCT in infants with cystic fibrosis (CF). MATERIALS AND METHODS: HRCT images of the lungs were obtained at four anatomical levels in 16 sedated children (age 2.4+/-1.1 years, mean+/-SD) with CF using controlled ventilation at full lung inflation (CVCT-I), at resting end exhalation (CVCT-E), and during quiet breathing (CT-B). Two blinded reviewers independently and then by consensus scored all images for the presence or absence of bronchiectasis (BE), bronchial wall thickening (BWT), and AT. RESULTS: Of the 64 images evaluated, BE was identified in 19 (30%) of the CVCT-I images compared to 6 (9%) of the CVCT-E images (P=0.006) and 4 (6%) of the CT-B images (P=0.044). AT was seen in 29 (45%) of the CVCT-E images compared to 14 (22%) of the CVCT-I images (P=0.012) and 12 (19%) of the CT-B images (P=0.012). There were no significant differences in the detection of BWT among the three methods. SUMMARY: In infants with CF, fully inflating the lung improved the ability to diagnose early BE, and obtaining motion-free images at end exhalation enhanced the detection of AT.

Lateral thoracic expansion for Jeune syndrome: evidence of rib healing and new bone formation.

BACKGROUND: Lateral thoracic expansion is a procedure that has been described to enlarge the thoracic cage in patients with Jeune's asphyxiating thoracic dystrophy. The procedure involves separating ribs from their periosteum and plating them together in an expanded fashion with titanium struts. We have speculated that the ribs heal in this situation, despite the absence of surrounding periosteum, and that new rib formation occurs in the liberated periosteum. METHODS: Radiographic studies of patients who have undergone lateral thoracic expansion were reviewed for evidence of rib healing or periosteal new bone formation. RESULTS: This study presents radiologic evidence that rib healing actually occurs, as does periosteal ossification. CONCLUSIONS: Lateral thoracic expansion creates additional chest wall that is formed of autologous tissue, fully healed, and not ultimately dependent on titanium struts.

Coincidence FDG-PET in the evaluation of Langerhans' cell histiocytosis: preliminary findings.

BACKGROUND: Bone involvement in Langerhans' cell histiocytosis (LCH) is common. Both bone scintigraphy and plain films are used to identify osseous lesions, but lack specificity for disease activity and response to therapy. FDG-PET is a sensitive technique for identifying bone lesions when histiocytes are present. OBJECTIVE. To describe the potential of coincidence FDG-PET (cFDG-PET) for identification of active bone lesions in LCH and to determine whether it can provide more specific information regarding lesional response to therapy than bone scintigraphy or radiography. MATERIALS AND METHODS: The clinical data and imaging findings of three patients with osseous lesions of LCH were retrospectively reviewed. RESULTS: cFDG-PET identified all active LCH osseous lesions in these patients, differentiated active from healed lesions, and demonstrated normalization of uptake in a treated lesion earlier than bone scintigraphy and radiography. CONCLUSION: cFDG-PET appears to have greater specificity than bone scintigraphy and radiography for the identification of active osseous lesions in LCH. It also may predict response to treatment earlier than conventional techniques. Its use in the evaluation of LCH warrants further study.

Congenital piriform fossa sinus tract presenting as an asymptomatic neck mass in an infant.

BACKGROUND: A 5-month-old girl with an asymptomatic left-sided neck mass was demonstrated by ultrasound and upper gastrointestinal series (UGI), and confirmed at surgery, to have a congenital piriform fossa sinus tract (CPFST) that communicated with an intrathyroidal cyst. OBJECTIVE: To demonstrate a case of CPFST presenting as an asymptomatic neck mass. Nearly all cases of CPFST present with infection or pain, making this case unique. MATERIALS AND METHODS: Case report and review of the literature. CONCLUSIONS: CPFST with an associated cyst should be added to the differential diagnosis of asymptomatic cystic neck masses in infants, especially if the cyst is intrathyroidal by ultrasound.