Simultaneous Bilateral Total Knee Arthroplasty and the Effects of Physical Therapy in the Outpatient Setting: A Case Study.

Background and Purpose: A bilateral total knee arthroplasty (TKA) is a surgical procedure that has seen success in managing end-stage osteoarthritis of the knee joint. This case study evaluates the usefulness of physical therapy following bilateral TKA and deliberates the outcomes the patient experienced. Case Description: The patient was a 62-year-old male who received postoperative physical therapy in an outpatient orthopedic clinic for a total of 8 weeks. The patient demonstrated decreased bilateral knee range of motion (ROM), decreased bilateral gross lower extremity (LE) strength, increased pain and swelling in both knees, and decreased endurance for ambulation. Intervention: Therapy provided to the patient emphasized the use of traditional TKA exercises as well as functional exercises. These exercises were used to assist in increasing bilateral knee ROM, bilateral knee strength, and the overall functional mobility of the patient. Outcomes: Throughout the course of treatment, the patient was able to increase his knee ROM bilaterally, LE strength, decrease his pain and swelling, and increase his endurance for ambulation. Discussion: The patient responded favorably to treatment, and many of the goals created were achieved. A clinical practice guideline on the management of total knee arthroplasty was recently released during the writing of this case study, and it can be referenced for the most current research on the examination and treatment for patients with total knee replacement

Genetic counseling for congenital heart disease – Practice resource of the national society of genetic counselors

Congenital heart disease (CHD) is an indication which spans multiple specialties across various genetic counseling practices. This practice resource aims to provide guidance on key considerations when approaching counseling for this particular indication while recognizing the rapidly changing landscape of knowledge within this domain. This resource was developed with consensus from a diverse group of certified genetic counselors utilizing literature relevant for CHD genetic counseling practice and is aimed at supporting genetic counselors who encounter this indication in their practice both pre- and postnatally

TCEAL1 Loss-of-Function Results in an X-Linked Dominant Neurodevelopmental Syndrome and Drives the Neurological Disease Trait in Xq222 Deletions

An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving TCEAL1 in seven unrelated families: three hemizygous truncating alleles; one hemizygous missense allele; one heterozygous TCEAL1 full gene deletion; one heterozygous contiguous deletion of TCEAL1, TCEAL3, and TCEAL4; and one heterozygous frameshift variant allele. Variants were identified through exome or genome sequencing with trio analysis or through chromosomal microarray. Comparison with previously reported Xq22 deletions encompassing TCEAL1 identified a more-defined syndrome consisting of hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features include strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. An additional maternally inherited hemizygous missense allele of uncertain significance was identified in a male with hypertonia and spasticity without syndromic features. These data provide evidence that TCEAL1 loss of function causes a neurological rare disease trait involving significant neurological impairment with features overlapping the EONDT phenotype in females with the Xq22 deletion

DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins

Does supply equal demand? The workforce of direct patient care genetic counselors in Wisconsin

BACKGROUND: Recent studies documented a shortage of direct patient care (DPC) genetic counselors in the United States. We aimed to survey genetic counselor members of the Wisconsin Genetic Counselors Association (WIGCA) to determine if the supply and demand was met within the state and where access to services can improve. METHODS: An email invitation was sent to all genetic counselor members of the WIGCA with a link to a confidential online survey. Survey questions addressed the workforce composition, elements that impact services, and professional satisfaction of practicing genetic counselors. RESULTS: The Wisconsin workforce currently has half of the projected need for full-time DPC genetic counselors. One-third of genetic counselors reported changing from direct to non-direct patient care positions. In-person services are concentrated within Milwaukee and Madison. Appointment wait times are decreased when patients meet with a genetic counselor only, and half of the genetic counselors reported moderate to high stress levels. DISCUSSION/CONCLUSION: A shortage of DPC genetic counselors in Wisconsin is confirmed due to the total full-time effort in direct patient care. Data provided here can be used to identify targets for increasing the number of DPC genetic counselors, maximizing time spent on patient care, and improving access

TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions

An Xq22.2 region upstream of PLP1 has been proposed to underly a neurological disease trait when deleted in 46,XX females. Deletion mapping revealed that heterozygous deletions encompassing the smallest region of overlap (SRO) spanning six Xq22.2 genes (BEX3, RAB40A, TCEAL4, TCEAL3, TCEAL1, and MORF4L2) associate with an early-onset neurological disease trait (EONDT) consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and dysmorphic facial features. None of the genes within the SRO have been associated with monogenic disease in OMIM. Through local and international collaborations facilitated by GeneMatcher and Matchmaker Exchange, we have identified and herein report seven de novo variants involving TCEAL1 in seven unrelated families: three hemizygous truncating alleles; one hemizygous missense allele; one heterozygous TCEAL1 full gene deletion; one heterozygous contiguous deletion of TCEAL1, TCEAL3, and TCEAL4; and one heterozygous frameshift variant allele. Variants were identified through exome or genome sequencing with trio analysis or through chromosomal microarray. Comparison with previously reported Xq22 deletions encompassing TCEAL1 identified a more-defined syndrome consisting of hypotonia, abnormal gait, developmental delay/intellectual disability especially affecting expressive language, autistic-like behavior, and mildly dysmorphic facial features. Additional features include strabismus, refractive errors, variable nystagmus, gastroesophageal reflux, constipation, dysmotility, recurrent infections, seizures, and structural brain anomalies. An additional maternally inherited hemizygous missense allele of uncertain significance was identified in a male with hypertonia and spasticity without syndromic features. These data provide evidence that TCEAL1 loss of function causes a neurological rare disease trait involving significant neurological impairment with features overlapping the EONDT phenotype in females with the Xq22 deletion