Fetal MR imaging of Kniest dysplasia.

We present a case of Kniest dysplasia, a rare form of the type II collagenopathies, with prenatal MRI. Sonography revealed only short limbs in the fetus. Fetal MRI findings included enlarged hyaline cartilaginous structures with abnormally high T2 signal intensity, delayed ossification of the pubic and ischial bones, and platyspondyly. By delineating the cartilaginous abnormalities, fetal MRI can contribute to the prenatal diagnosis of chondrodysplasias.

Experience with hemihyperplasia and Beckwith-Wiedemann syndrome surveillance protocol.

Beckwith-Wiedemann syndrome (BWS) and isolated hemihyperplasia (IHH) are two well known overgrowth conditions that are associated with cancer predisposition. Multiple surveillance protocols have been proposed to detect the most commonly reported tumor types Wilms tumor and hepatoblastoma. We reviewed the history of our patients who were part of this monitoring protocol. Information from 63 cases was collected retrospectively while another 63 control samples for AFP measurement were obtained prospectively. Twenty-five (40%) patients had an ultrasound abnormality, the most frequent being nephromegaly/size discrepancy. Two patients had well documented cases of tumors/tumor precursor (2/63:3.2%) detected by ultrasound images. Three hundred thirty-six separate AFP values were available with values above 50,000 ng/ml seen in three patients older than 2 months, one with hepatoblastoma and two other with hemangiomas/hemangioendotheliomas. There was no clear difference in the range of AFP values between previously reported controls, our own normal population and affected patients. In conclusion, ultrasound surveillance detected renal and liver pathology including benign and malignant lesions. The known variability of AFP in normal neonates and patients with BWS makes interpretation difficult in early infancy. Very high AFP values did seem to be correlated with risk for identifiable liver lesions. Determination of the natural changes in AFP levels over time will allow more appropriate comparison.

Enzyme reconstitution/replacement therapy for lysosomal storage diseases.

PURPOSE OF REVIEW: Over the past 15 years, the lysosomal storage diseases have become paradigms for the specific treatment of monogenic disorders, particularly those affecting children. This review summarizes the phenotypes and recent literature regarding enzyme reconstitution (replacement) therapy and outcomes for such treatable lysosomal storage diseases: Gaucher disease, Fabry disease, Pompe disease and the mucopolysaccharidoses. RECENT FINDINGS: Recent clinical trials have shown that enzyme reconstitution therapy effectively treats many of the manifestations of the lysosomal storage diseases. When initiated early in the disease course, enzyme reconstitution therapy can reverse some disease manifestations, but may not completely alleviate the disease progression. Enzyme reconstitution therapy is generally well tolerated. Many adverse events are antibody-related, but can be managed without requiring cessation of enzyme reconstitution therapy. Documented IgE reactions, i.e. anaphylactoid, are quite rare (fewer than 1%). SUMMARY: Enzyme reconstitution therapy is a safe and effective treatment modality available for several of the lysosomal storage diseases. Owing to the short history of enzyme reconstitution therapy, the long-term outcomes of enzyme reconstitution therapy-treated individuals are unknown and require further investigation. Medical professionals must learn to identify patients likely to benefit from these life-changing therapies so as to prevent many of the devastating, irreversible complications of the lysosomal storage diseases.

Novel fibrillin 1 mutation in a case of neonatal Marfan syndrome: the increasing importance of early recognition.

Neonatal Marfan syndrome (MFS) is a severe form of classic MFS caused by mutations in a specific region of the fibrillin 1 gene (FBN1). We report a case of an infant with neonatal MFS who presented with flexion contractures in utero and severe skeletal and cardiovascular manifestations at birth. A novel de novo missense mutation in exon 26 of FBN1 was demonstrated. Because of potential new therapies, it is increasingly important to recognize neonatal MFS in utero as well as shortly after birth to initiate the appropriate diagnostic work-up and management.