Individuals with genetic disorders present with multisystem, complex, and special health care needs. Although limited treatment options are available for most genetic conditions, ensuring continued ...ongoing surveillance and rehabilitative care is quintessential for improving their quality of life. Delivering comprehensive health-care directed at periodic surveillance, timely diagnosis, and specialized management of these individuals warrants ongoing evaluation and management by specialists in multiple disciplines. Multidisciplinary team approach involving coordinated care among various specialties with a patient-centric outlook ensures efficient resource utilization and cost-effective management. The establishment of “one-stop” multidisciplinary specialized clinics providing comprehensive care is expected to improve the quality of patient care and reduce the overall burden on the family.
Down syndrome is the commonest chromosomal disorder causing mild to moderate intellectual disability, yet it is one of the neglected disorder amongst practicing physicians. Children with Down ...syndrome when intervened early by speech therapy, physiotherapy and occupational therapy and given proper medical attention for different health issues, can have a better long term outcome as compared to other genetic causes of intellectual disability. This paper would help the general practitioners to identify children with Down syndrome and to manage the common problems associated with this condition.
Intellectual disability (ID) is a common cause of referral to the pediatricians, geneticists, and pediatric neurologists. A thorough clinical evaluation and a stepwise investigative approach using a ...combination of traditional genetic techniques and appropriate latest genomic technologies can help in arriving at a diagnosis. In the current “omics” era, adopting a multiomics approach would further assist in solving the undiagnosed cases with intellectual disability.
To report a case of diffuse xanthogranuloma presenting as bilateral anterior uveitis in a neonate.
A neonate was brought by the parents with complaints of redness, watering, and photophobia in both ...eyes for 10 days. Examination under anesthesia revealed the presence of bilateral hyphema, fibrinous membrane, corneal haze, and raised intraocular pressure (IOP). Ultrasound Biomicroscopy revealed diffuse bilateral iris thickening. The child was managed medically with topical glaucoma medications, topical steroids, and cycloplegics. The child responded well with the resolution of hyphema, anterior chamber inflammation, and reduction of IOP.
In neonates and infants presenting with bilateral uveitis, spontaneous hyphema, and secondary glaucoma, even in the absence of a well-defined iris lesion, diffuse juvenile xanthogranuloma should be considered as a differential diagnosis.
Secretary of Commerce Henry A. Wallace was an earnest supporter of the Stimson Proposal, a disarmament proposal submitted to the Truman administration by then Secretary of War Henry L. Stimson ...immediately after World War II. This proposal suggested direct dialogue with the Soviets over control of the newly-released atomic energy used against Japan in August 1945.Wallace, who had nurtured a deep scientific knowledge in his early life, was trusted in his Vice Presidency (1941-1945) for his scientific skills by not only President Franklin D. Roosevelt, but also scientific administrator Vannevar Bush. Because of this, Wallace's postwar vision was similar to Stimson's Proposal and the views of atomic scientists, who believed that basic scientific knowledge could not be contained because science had no national boundaries. Why was Wallace so thoroughly neglected by incumbent President Harry S. Truman and his fellow policy-makers? Wallace's idea, basically encouraging a joint partnership with the Soviets, failed to find favor with Truman, his aides, and the American public. Their belief was that the US's secret of atomic bomb was a national asset.This book illustrates that Wallace's idea of international atomic controls with Soviet partnership - a position embraced by atomic scientists - could prevent a postwar nuclear proliferation. The failure of Wallace's concept of postwar world order, a product of rejection by President Truman, has revealed an ideological conflict between democracy and nuclear weaponry. Amazingly, Wallace daringly made this historic attempt and kept to his vision, a commitment which led to his alienation and eventual ousting from Truman's cabinet.
Skeletal dysplasias or osteochondrodysplasias comprise a large heterogeneous group of genetic disorders and possess significant overlap on imaging, which adds to the dilemma of the reporting ...radiologist. These entities are routinely evaluated with a detailed skeletal survey and hand radiographs form a crucial part of a complete survey. Certain conditions have characteristic imaging findings that enable a diagnosis be made on hand radiograph alone. Additionally, hand radiographs may also demonstrate findings that may be suggestive of a particular diagnosis/differential diagnoses and would warrant further assessment for proving the same. We aim to demonstrate the use of hand radiographs in diagnosis of various such entities through this review. Although they cannot replace a complete skeletal survey in the diagnosis, hand radiographs performed for other indications might alert a radiologist to the diagnosis of an unsuspected skeletal dysplasia.
Abstract
Background
Structured reporting has the advantages of reducing ambiguity in written radiology reports with greater uniformity and comparability of reports amongst different institutes. It ...has multiple facets: structured format, structured content, and standardized language. While structured reporting initiative has been used in various radiology subspecialties such as oncology, cardiothoracic, abdominal and interventional radiology; skeletal dysplasia is a domain that remains largely untouched by this concept.
Purpose
To evaluate the impact of structured reporting in skeletal dysplasia.
Methods and Materials
This was an ethically approved pragmatic clinical trial. A defined number (75) of clinically diagnosed and/or genetically confirmed skeletal dysplasia radiographs were evaluated by two radiologists (reader A and reader B) with 5-and 7-years' experience in general radiology, respectively. A pre-defined structured reporting format for skeletal dysplasia was used as an interventional tool. Both the readers interpreted the radiographs before and after the training session. In addition to diagnosis, diagnostic confidence was noted using a semiquantitative scale. Improvement in diagnostic accuracy and diagnostic confidence after training were assessed. McNemar's test was used to assess the statistical significance of difference in proportion of correct diagnoses in pre- and post-education phases. An interrater reliability analysis using the Kappa statistic was performed to determine interobserver agreement between readers both in pre- and post-education phases.
Results
In the post-education phase, the proportion of accurate diagnosis improved from 48% (36/75) to 64% (48/75) for reader A, and from 44% (33/75) to 60% (45/75) for reader B as compared with the pre-education phase. Amongst the cases with a correct radiologic diagnosis, an increase in diagnostic confidence was noted in 18 cases for reader A, and 15 cases for reader B. In none of the cases, there was a reduction in diagnostic confidence after training. A McNemar's test determined that there was a statistically significant difference in the proportion of correct diagnoses in pre- and post-education phases,
p
< 0.001. The interobserver agreement between the readers was found to increase from Kappa = 0.33 (
p
= 0.004) using non-structured reporting in pre-education phase to Kappa = 0.46 (
p
< 0.001) using structured reporting in the post-education phase.
Conclusion
A structured reporting of skeletal survey can improve accuracy and confidence in diagnosing skeletal dysplasia.
Asparagine synthetase deficiency is a rare inborn error of metabolism caused by a defect in
ASNS
, a gene encoding asparagine synthetase. It manifests with a severe neurological phenotype manifesting ...as severe developmental delay, congenital microcephaly, spasticity and refractory seizures. To date, nineteen patients from twelve unrelated families have been identified. Majority of the mutations are missense and nonsense mutations in homozygous or compound heterozygous state. We add another case from India which harbored a novel homozygous missense variation in exon 11 and compare the current case with previously reported cases.
Joubert syndrome and related disorders (JSRDs) are genetically heterogeneous and characterized by a distinctive mid-hindbrain malformation. Causative mutations lead to primary cilia dysfunction, ...which often results in variable involvement of other organs such as the liver, retina, and kidney. We identified predicted null mutations in CSPP1 in six individuals affected by classical JSRDs. CSPP1 encodes a protein localized to centrosomes and spindle poles, as well as to the primary cilium. Despite the known interaction between CSPP1 and nephronophthisis-associated proteins, none of the affected individuals in our cohort presented with kidney disease, and further, screening of a large cohort of individuals with nephronophthisis demonstrated no mutations. CSPP1 is broadly expressed in neural tissue, and its encoded protein localizes to the primary cilium in an in vitro model of human neurogenesis. Here, we show abrogated protein levels and ciliogenesis in affected fibroblasts. Our data thus suggest that CSPP1 is involved in neural-specific functions of primary cilia.
Abstract Introduction Autonomic dysfunctions are common in children with Rett syndrome. They usually manifest with agitation, persistent screaming, constipation, gastroesophageal reflux, aerophagia, ...hyperventilation and breath holding spells. Cardiovascular autonomic dysfunction are known which at times may result in fatal arrhythmias. Many of these events are mistaken as seizures and treated with antiepileptics. Methods The current study was conducted in a tertiary care teaching hospital in north India over a 6 month period. MeCP2 mutation positive, 24 cases with Rett syndrome and 24 healthy age matched girls, were evaluated for cardiovascular autonomic dysfunction { heart rate variability (HRV), head up tilt (HUT) test and cold pressor test (CPT)}. Results The mean age in years was 9.06 (+/- 3.4) and 9.75 (+/- 3.13) for patients and controls respectively. The HRV contributed independently by parasympathetic and sympathetic nervous system was significantly reduced in cases as compared to controls (p=0.033 and p=0.001 respectively). There was significant sympathovagal imbalance with sympathetic overactivity in cases as compared to controls (p=0.001). The mean longest QTc interval was significantly prolonged in cases compared to controls (p=0.001). CPT and HUT could be done in 16 RTT patients (due to poor cooperation) and in all 24 controls. The change in blood pressure during CPT and HUT was not significantly different in cases and controls. Conclusion Children with Rett syndrome were observed to have significant cardiovascular autonomic dysfunction in the form of sympathetic overactivity, parasympathetic underactivity and sympathovagal imbalance. This has got important therapeutic and outcome related implications.
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