Anterior cervical discectomy and fusion for the treatment of pediatric Hirayama disease.

PURPOSE: Hirayama disease, a rare cervical myelopathy in children and young adults, leads to progressive upper limb weakness and muscle loss. Non-invasive external cervical orthosis has been shown to prevent further neurologic decline; however, this treatment modality has not been successful at restoring neurologic and motor function, especially in long standing cases with significant weakness. The pathophysiology remains not entirely understood, complicating standardized operative guidelines; however, some studies report favorable outcomes with internal fixation. We report a successful surgically treated case of pediatric Hirayama disease, supplemented by a systematic review and collation of reported cases in the literature. METHODS: A review of the literature was performed by searching PubMed, Embase, and Web of Science. Full-length articles were included if they reported clinical data regarding the treatment of at least one patient with Hirayama disease and the neurologic outcome of that treatment. Articles were excluded if they did not provide information on treatment outcomes, were abstract-only publications, or were published in languages other than English. RESULTS: Of the fifteen articles reviewed, 63 patients were described, with 59 undergoing surgery. This encompassed both anterior and posterior spinal procedures and 1 hand tendon transfer. Fifty-five patients, including one from our institution, showed improvement post-treatment. Eleven of these patients were under 18 years old. CONCLUSION: Hirayama disease is an infrequent yet impactful cervical myelopathy with limited high-quality evidence available for optimal treatment. The current literature supports surgical decompression and stabilization as promising interventions. However, comprehensive research is crucial for evolving diagnosis and treatment paradigms.

Onasemnogene Abeparvovec Treatment after Nusinersen in an Infant with Spinal Muscular Atrophy Type 1.

BACKGROUND: Until recently, the treatment of spinal muscular atrophy (SMA) was limited to symptomatic treatment with no cure. Three innovative drugs, nusinersen, onasemnogene abeparvovec (OA), and risdiplam have been developed to treat SMA. Although the clinical trials for these drugs have demonstrated their efficacy, there is limited information on real world treatment strategies. In this study, we present a case of a male infant with SMA type 1 who underwent OA treatment after nusinersen treatment. CASE PRESENTATION: At 4 months of age, the patient was diagnosed with SMA type 1. At 6 months of age, nusinersen treatment was initiated. His motor function improved, but the effect was limited; therefore, his parents requested gene replacement therapy. During the preparation for OA treatment, anti-adeno-associated virus 9 (AAV9) antibody tests repeatedly showed non-specific reactions, which delayed initiation of treatment. The patient was put on ventilator management after he caught a common cold. During this management, the anti-AAV9 antibody test results were negative. Furthermore, the patient showed increased transaminase levels just before OA treatment; however, since these gradually decreased without signs of liver failure, we started OA treatment at 13 months of age. Four months later, the patient began to sit without support and was weaned from non-invasive positive pressure ventilation, although nasogastric tube feeding remained partially necessary. CONCLUSION: We believe that the management of unstable SMA type 1 symptoms, anti-AAV9 antibody testing, and changes in transaminase levels will be helpful for other patients with SMA who require treatment.

Single-institution Series of Hirayama Disease in North America.

STUDY DESIGN: A retrospective chart review. OBJECTIVE: The aims of this study were to review pathophysiology, workup, and treatment for Hirayama disease (HD); and to assess outcomes from a single institution. SUMMARY OF BACKGROUND DATA: HD is a rare, painless, cervical myelopathy with distal upper extremity weakness, muscle wasting, and spinal cord atrophy. Disease progression-a consequence of repeat flexion injury-occurs up to 5 years from the initial diagnosis. METHODS: Single-institution review of pediatric HD patients from 2010 to 2020. RESULTS: Patients (n=10 male, n=2 female) presented in the second decade (14-20 y) with painless progressive distal upper extremity weakness and atrophy without sensory loss. Electromyography (n=12) demonstrated denervation in C7-T1 myotomes and flexion/extension magnetic resonance imaging showed focal cord atrophy and anterior displacement of the posterior dura with epidural enhancement in flexion. Treatment included observation and external orthoses (n=9) and anterior cervical discectomy with fusion (n=3). One of the 9 patients managed conservatively experienced further deterioration; no patient who underwent anterior cervical discectomy with fusion progressed. CONCLUSIONS: Patients with HD require a multidisciplinary approach to diagnosis and treatment to preserve function. Treatment is preventive and aims to minimize flexion injury by inhibiting motion across involved joints. First-line management is avoidance of neck flexion and use of rigid orthosis; in cases of failed conservative management and/or rapid clinical deterioration, surgical fixation can be offered.

Monomelic Amyotrophy/Hirayama Disease: Surgical Outcome in a Large Cohort of Indian Patients.

BACKGROUND: Hirayama disease (HD) is a cervical compressive myelopathy. Anterior cervical discectomy and fusion (ACDF) is identified as the best surgical approach. We evaluated surgical outcomes and factors influencing ACDF in HD. METHODS: Between 2015 and 2019, 126 patients with HD underwent ACDF. Contrast magnetic resonance imaging of the cervical spine in full flexion was performed. Clinical examination and preoperative/postoperative assessment of hand function using Fugl-Meyer assessment, Jebsen-Taylor hand function test, and handheld dynamometry were performed at 3-monthly intervals for 1 year. Surgical outcomes were assessed as per the Odom criteria and Hirayama outcome questionnaire. RESULTS: Age at onset and duration of illness were 12-31 years (mean, 18 ± 2.7) and 1-96 months (32.7 ± 24.4), respectively. All patients had progressive weakness and wasting of the affected limb. Cord atrophy was seen in 97.1%, with epidural detachment and engorgement of the posterior epidural venous plexus in all. All patients underwent ACDF. Of these patients, 54% had an excellent/good outcome and 39% had a satisfactory outcome as per the Odom scale at last follow-up (mean, 44.9 ± 16.5 months) after surgery. Handheld dynamometry showed improvement from preoperative values to 1 year follow-up. Duration of illness and age at onset had a negative correlation and the preoperative Fugl-Meyer score had a positive correlation with improvement. CONCLUSIONS: ACDF resulted in remarkable improvement or stabilization in neurologic deficits in many patients with HD. Because motor disability ensues over time, early surgical intervention during the progressive phase is advocated.

Spinal Muscular Atrophy Type III Recognized After Delayed Recovery From Neuromuscular Blockade After an Orthognathic Surgery.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by the degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. SMA is classified into types I-IV based on the age at symptom onset or maximum motor function achieved, and its clinical manifestations vary. SMA affects maxillofacial growth because of muscle dysfunction and results in abnormal maxillofacial morphology. In addition, definitive diagnosis is not often made because of the older onset age and symptoms are rarely severe. Therefore, the possibility of undiagnosed SMA in craniofacial surgeries must be considered. This report described a case of an SMA type III recognized after delayed recovery from the neuromuscular blockade in an orthognathic surgery under general anesthesia.

Outcome of Tendon Transfer for Monomelic Amyotrophy (Hirayama Disease).

Hirayama disease is a motor neuron disease predominantly affecting adolescent males. The identifying feature of Hirayama disease is unilateral forearm and intrinsic muscle weakness that spares the brachioradialis, termed "oblique atrophy." Hirayama disease progresses slowly over several years, followed by an abrupt arrest. The pathognomonic finding is the anterior displacement of the cervical spinal cord with the detachment of the posterior dura. Systematic clinical evaluation and appropriate diagnostic studies are crucial to rule out a variety of compressive, immune-mediated, and genetic disorders. We present a patient with Hirayama disease whose hand function was improved dramatically by a tendon transfer after nearly 3 years without a definitive diagnosis and call attention to the hand surgeon's role in identifying this rare disease to enable timely functional restoration.

Flexible endoscopic evaluation of swallowing in children with type 1 spinal muscular atrophy.

PURPOSE: This study aimed to report on implementing flexible endoscopic evaluation of swallowing (FEES) in infants and toddlers with type 1 spinal muscular atrophy (SMA). In addition, a comparison of FEES results and clinical scores was carried out. METHODS: A prospective pilot study was conducted including ten symptomatic children with SMA type 1 (two SMN2 copies). They started treatment with one of the three currently approved therapies for SMA at a median age of 3.8 months (range 0.7-8.9). FEES was performed according to a standard protocol using Penetration-Aspiration Scale (PAS) and Murray Secretion Scale as a primary outcome. The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) for motor function, Neuromuscular Disease Swallowing Status Scale (NdSSS), Oral and Swallowing Abilities Tool (OrSAT), and single clinical swallowing-related parameters were also assessed. RESULTS: Distinct swallowing disorders were already evident in eight children at inclusion. The most common findings from FEES were pharyngeal secretion pooling, penetration, and aspiration of saliva and food as well as delayed initiation of swallowing. Despite an average increase in motor function, no comparable improvement was found in swallowing function. None of the surveyed clinical scores showed a significant dependence on PAS in a mixed linear model. CONCLUSIONS: Valuable information regarding the status of dysphagia can be gathered endoscopically, particularly concerning secretion management and when oral intake is limited. Currently available clinical tools for children with type 1 may represent a change in nutritional status but are not yet mature enough to conclude swallowing ability. Further development is still required.

Evaluation of cerebrospinal fluid biomarkers in pediatric patients with spinal muscular atrophy.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterised by muscle weakness and muscle atrophy and classified into five known subtypes based on clinical features. The recent development of novel drugs to treat SMA has been encouraging, and nusinersen is the first drug approved to treat SMA. OBJECTIVE: To explore cerebrospinal fluid (CSF) biomarkers of SMA and investigate their relationship with symptoms and the treatment response in pediatric patients. METHODS: We analyzed the CSF levels of chitotriosidase 1 (CHIT1) and inflammatory cytokines (tumor necrosis factor [TNF]-α and interferon [INF]-γ) using enzyme-linked immunosorbent assays in pediatric SMA patients treated at Hiroshima University Hospital over 2 years. RESULTS: This study analyzed pediatric SMA patients. While the CSF inflammatory cytokines (TNF-α and INF-γ) in these SMA children were unchanged, the CHIT1 levels decreased significantly from year 1 to 2 of treatment. We also found a trend toward an inverse correlation between the motor function score (HINE-2 scores) and CHIT1 level from year 1 to 2 of treatment. CONCLUSIONS: CHIT1 may be a CSF biomarker of the treatment response in pediatric SMA.

Finger trembling improvement after surgery in Hirayama disease: a case report.

INTRODUCTION: Finger trembling is a characteristic physical finding in Hirayama disease. Although conservative treatment is recommended to stop disease progression, surgery is optional in some cases. However, the postoperative recovery of finger trembling is scarcely reported. CASE PRESENTATION: A 26-year-old Japanese female patient whose chief complaint was left finger trembling with active finger extension presented at our hospital. Hand weakness without muscle atrophy of the left arm was observed. MRI showed left-side oriented intramedullary signal change with concomitant cord atrophy at C4-5 and C5-6. The CT myelogram (CTM) on flexion showed anterior cord compression and anterior shift of posterior dura matter from C4 to C6. And CTM on extension showed the resolution of both findings. Electrophysiological studies showed active and chronic neuronal damage and preserved motor neuron pool of hand muscle. Since she had exhibited a gradual aggravation of symptoms over a period of 5 years, she underwent anterior cervical discectomy and fusion after careful assessment of both conservative and surgical treatment. Finger trembling recovered soon after surgery. DISCUSSION: Finger trembling is an unfamiliar physical finding in terms of postoperative recovery prediction. Anterior horn cell impairment is postulated as a cause of finger trembling. Postural restoration of spinal cord shape and cerebrospinal fluid around the cord with preserved neural function could facilitate functional recovery.

Biomarkers of disease progression in adolescents and adults with 5q spinal muscular atrophy: a systematic review and meta-analysis.

Since the introduction of disease modifying treatments there is an unmet need to identify biomarkers of spinal muscular atrophy (SMA) natural history. We performed a systematic review and meta-analysis to summarize available evidence. We searched MEDLINE, Embase, Cochrane Library and gray literature until February 2021. The primary outcome was biomarkers longitudinal course in adolescents and adults. The secondary outcome was the discrimination of patients from controls. We included 42 records examining 606 patients from 19 population cohorts over a maximum follow-up of 17-years. Lung function and serum biomarkers could not depict disease progression. We identified potential biomarkers of disease activity [SMA functional rating scale, MoviPlate, pinch strength, compound muscle action potential (CMAP), motor unit number estimation (MUNE)] that require further investigation. Data regarding Hammersmith functional motor scale expanded, Revised upper limb module, 6-minute walk test were contradictory impeding any pooled estimate. The pooled analysis regarding our secondary outcome revealed that upper limb CMAP amplitudes and MUNE mean values differed significantly between SMA patients and controls [mean difference -3.63(-6.2, -1.06), -119.74(-153.93, -85.56) respectively]. Given the lack of natural history data on this population, our qualitative synthesis and meta-analysis could provide valuable evidence and identify promising predictive biomarkers requiring further longitudinal examination. PROSPERO Registration: CRD42021235605.

A patient with early-onset SMAX3 and a novel variant of ATP7A.

OBJECTIVE: To describe clinical and genetic studies on a patient with early-onset spinal muscular atrophyX3 (SMAX3) with novel variant of ATP7A. METHODS: Clinical, neurophysiological, neuroimaging and pathological examinations were performed. Whole exome sequencing was applied to search genetic bases of this patient. RESULTS: The patient had gait abnormality from early infantile period. Muscle imaging at 42 years old showed predominant involvement of proximal muscles as compared to the distal muscles. The patient had a novel variant of ATP7A, which was the fourth genotype of ATP7A exhibited as SMAX3. Contrary to previous reports of distal motor neuropathy, the clinical and neuroimaging findings in this case revealed dominant involvement in the proximal portion of the extremities and trunk, which is similar to patients with type III SMA. CONCLUSION: The dominant involvement of proximal motor system in this patient may expand the phenotypic variability of SMAX3. We need to be aware of this disorder in differential diagnosis of patients with type III SMA-like phenotype.

Hirayama Disease in a Patient with a History of Late-Onset Symptomatic Vein of Galen Aneurysmal Malformation.

INTRODUCTION: The purpose of this report is to present a rare case of Hirayama disease (HD) in a patient with a history of late-onset symptomatic vein of Galen aneurysmal malformation (VGAM). This report may provide new insights into the pathophysiology of HD, a rare disorder consisting of insidious onset of unilateral weakness and atrophy of the forearm and intrinsic hand muscles. These symptoms are believed to result from cervical myelopathy affecting the anterior horn cells due to abnormal compressive forces on the spinal cord from adjacent anatomical structures (i.e., dura and/or epidural veins), but this has not been proven. VGAM is a rare congenital cerebral vascular malformation, consisting of high-flow arteriovenous shunting between a persistent median prosencephalic vein and arterial feeders, which most frequently presents in the early neonatal period with congestive heart failure. CASE PRESENTATION: We report the case of an otherwise healthy boy who presented with heart failure due to VGAM at 7 years and subsequently presented at 14 years with left-sided HD. His cervical MRI with neck flexion revealed enlarged epidural veins at the C5-C6 spinal level with anterior, leftward displacement of the posterior dura and spinal cord as well as left hemicord flattening and/or atrophy at this level. He underwent successful surgical treatment by C5-C6-C7 osteoplastic laminotomies and tenting and expansile autologous duraplasty, during which enlarged, engorged epidural veins were confirmed and coagulated. This halted the progression of his left hand weakness and atrophy and allowed significant functional improvement. Postoperative catheter angiogram showed no anatomical connection between the persistent VGAM and the engorged epidural veins, and genetic testing revealed no genetic predisposition of vascular malformations. DISCUSSION/CONCLUSION: In this patient, a combined surgical technique was performed that included epidural venous plexus coagulation with posterior autologous duraplasty and dural fixation using tenting sutures. This combined approach led to a favorable clinical and radiographic outcome with no complications or limitations and has not been previously proposed in the literature, to our knowledge. Although not completely ruled out, we found no angiographic connection or genetic predisposition to suggest there is a pathophysiological link between HD and VGAM.

A 5-year-old boy with acute neurological disorder from anteflexion-induced cervical cord compression after tracheal surgery: Radiological findings similar to Hirayama disease.

Constant neck flexion has been considered crucial to reducing anastomotic tension after tracheal resection. However, in rare cases, anteflexion can cause cervical cord damage, leading to acute neurological disorders such as tetraplegia. Here, we report a case of 5-year-old boy presenting with acute neurological disorder triggered by a chin-to-chest position over 4 days of deep sedation after cricotracheal resection. The radiological findings would suggest a mechanism similar to Hirayama disease, in which a shift of the dura leads to chronic muscular weakness and atrophy in young populations.

Clinical exome sequencing in the diagnosis of pediatric neuromuscular disease.

BACKGROUND: The diagnosis of uncommon pediatric neuromuscular disease (NMD) is challenging due to genetic and phenotypic heterogeneity, yet is important to guide treatment, prognosis, and recurrence risk. Patients with diagnostically challenging presentations typically undergo extensive testing with variable molecular diagnostic yield. Given the advancement in next generation sequencing (NGS), we investigated the value of clinical whole exome sequencing (ES) in uncommon pediatric NMD. METHODS: A retrospective cohort study of 106 pediatric NMD patients with a combination of ES, chromosomal microarray (CMA), and candidate gene testing was completed at a large tertiary referral center. RESULTS: A molecular diagnosis was achieved in 37/79 (46%) patients with ES, 4/44 (9%) patients with CMA, and 15/74 (20%) patients with candidate gene testing. In 2/79 (3%) patients, a dual molecular diagnosis explaining the neuromuscular disease process was identified. A total of 42 patients (53%) who received ES remained without a molecular diagnosis at the conclusion of the study. CONCLUSIONS: Due to NGS, molecular diagnostic yield of rare neurological diseases is at an all-time high. We show that ES has a higher diagnostic rate compared to other genetic tests in a complex pediatric neuromuscular disease cohort and should be considered early in the diagnostic journey for select NMD patients with challenging presentations in which a clinical diagnosis is not evident.

Respiratory Trajectories in Type 2 and 3 Spinal Muscular Atrophy in the iSMAC Cohort Study.

OBJECTIVE: To describe the respiratory trajectories and their correlation with motor function in an international pediatric cohort of patients with type 2 and nonambulant type 3 spinal muscular atrophy (SMA). METHODS: This was an 8-year retrospective observational study of patients in the International SMA Consortium (iSMAc) natural history study. We retrieved anthropometrics, forced vital capacity (FVC) absolute, FVC percent predicted (FVC%P), and noninvasive ventilation (NIV) requirement. Hammersmith Functional Motor Scale (HFMS) and revised Performance of Upper Limb (RULM) scores were correlated with respiratory function. We excluded patients in interventional clinical trials and on nusinersen commercial therapy. RESULTS: There were 437 patients with SMA: 348 with type 2 and 89 with nonambulant type 3. Mean age at first visit was 6.9 (±4.4) and 11.1 (±4) years. In SMA type 2, FVC%P declined by 4.2%/y from 5 to 13 years, followed by a slower decline (1.0%/y). In type 3, FVC%P declined by 6.3%/y between 8 and 13 years, followed by a slower decline (0.9%/y). Thirty-nine percent with SMA type 2% and 9% with type 3 required NIV at a median age 5.0 (1.8-16.6) and 15.1 (13.8-16.3) years. Eighty-four percent with SMA type 2% and 80% with type 3 had scoliosis; 54% and 46% required surgery, which did not significantly affect respiratory decline. FVC%P positively correlated with HFMS and RULM scores in both subtypes. CONCLUSIONS: In SMA type 2 and nonambulant type 3, lung function declines differently, with a common leveling after age 13 years. Lung and motor function correlated in both subtypes. Our data further define the milder SMA phenotypes and provide information to benchmark the long-term efficacy of new treatments for SMA.

Clinical features of spinal muscular atrophy (SMA) type 3 (Kugelberg-Welander disease).

Spinal muscular atrophy type 3 (SMA3), also called Kugelberg-Welander SMA, typically presents with muscle fatigue, slowly progressive weakness and atrophy of lower limbs once they have already acquired independent ambulation. Visceral involvement frequent in type 1 and 2 subtypes is rare in SMA3. Hypotonia, hyperlaxity and absent osteo-tendinous reflexes are typical features. By definition, standing or walking without support is achieved but the vast majority of SMA3 patients lose ambulation with time. Lifespan is normal. In some classifications, an additional subtype is included in the mild end of the spectrum, namely spinal muscular atrophy type 4 (SMA4). In this rare subtype, symptoms begin in adulthood; patients remain ambulatory at least until the fifth decade and have a normal respiratory function. Molecular genetic testing is the gold standard tool for diagnosis of SMA. However, diagnosis in a child affected with SMA3 is often challenging because clinical presentation mimics a muscular dystrophy. Electrodiagnostic studies and muscle biopsy are useful tools for demonstrating the presence of denervation but sometimes may not show meaningful differences to help distinguish between SMA and myopathy. Recent specific therapies show promising results before severe neuronal degeneration and motor dysfunction is installed. Therefore, high suspicion should be maintained and genetic analysis performed early in the diagnostic process when facing patients with symmetric and prominent proximal weakness, especially if they present progressive motor impairment. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Functional and surgical treatments in patients with spinal muscular atrophy (SMA).

Spinal muscular atrophies (SMA type 1, 2, 3) present with various severities according to the motor semeiology related to lesions of the peripheral nervous system (lesions of the anterior horn cells motoneuron or even brain stem). Early motor deficiency causes skeletal deformities responsible for the alteration or even absence of motor skills acquisition. The management of these patients involves several practitioners: pediatric neurologist, pediatric pneumologist, physical medicine and rehabilitation therapist, pediatric orthopedic surgeon, psychologist, physiotherapist, etc. Therefore, this multidisciplinary management must take place in a reference center. This has allowed for improvement of the natural history of SMA. Despite the severity of clinical presentation, especially in SMA type 1 or 2, the functional aspect is always to be taken into account in the first instance. Furthermore, the natural history of the disease is currently being modified by the emergence of innovative therapies that will change the evolution of the disease and its management. Indeed, current treatment objectives are the comfort of installation and the fight against neuro-orthopedic degradation. Although the rise in the number of innovative therapies has led to increased expectancies, such as motor function improvement, practitioners should be aware that these innovative treatments should be balanced against child development and the disease's natural history. Scoliosis surgery is almost systematic in SMA type 2 because of trunk muscular deficiency, especially intercostal muscle insufficiency, and spino-pelvic complex disorder. However, surgical techniques have evolved to become less invasive and more growth friendly in order to follow child development. The final goal of surgery in SMA patients is to obtain a 3-dimensional deformity correction along with a spino-pelvic realignment in order to allow for a comfortable seated position, which is the position of function in these patients, and to allow for better ventilation. Faced with this global approach and innovative therapies, global assessment is warranted not solely in an isolated manner, as is usually the case during hospital stays with traditional scales, but rather during daily activities. This is the case of daily monitoring, which allows for motor skill and activity assessments throughout the day. The principle is to characterize, according to SMA type and treatment, the activity type (standing, seated, walking), duration, intensity and frequency. The ultimate goal would be to identify the variety and occurrence of motor activities, and finally to clarify if the different treatments, including innovative therapies, lead to functional improvement in these patients. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Ethical aspects in the care of a child with infantile spinal muscular atrophy (SMA).

The pediatrician has a privileged relationship with a child with infantile spinal muscular atrophy (SMA). At all times, he/she must be the child's mentor, promoting a comprehensive approach and support in order to ensure the best possible solution for the patient's autonomy. In all circumstances, an ethical stance is essential. After a reminder on the notions of ethics of care, we will address various ethical questions encountered through three critical situations during the care of a child with infantile spinal muscular atrophy: the announcement of the diagnosis, the transmission of information on innovative therapies, and palliative care and end-of-life support. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Clinical Service Delivery of Noninvasive Prenatal Diagnosis by Relative Haplotype Dosage for Single-Gene Disorders.

A relative haplotype dosage (RHDO)-based method was developed and implemented into routine clinical practice for noninvasive prenatal diagnosis (NIPD) of multiple single-gene disorders: spinal muscular atrophy, Duchenne and Becker muscular dystrophies, and cystic fibrosis. This article describes the experiences of the first 152 pregnancies to have NIPD by RHDO as part of a routine clinical service. Provision of results within a clinically useful time frame (mean, 11 calendar days) was shown to be possible, with a very low failure rate (4%), none being due to a technical failure. Where follow-up confirmatory testing was performed for audit purposes, 100% concordance was seen with the NIPD result, and no discrepancies have been reported. The robust performance of the assay, together with high sensitivity and specificity, demonstrates that NIPD by RHDO is feasible for use in a clinical setting.

Prenatal diagnosis of rare genetic conditions at a tertiary care hospital in Karachi.

This study aims to observe the spectrum of Prenatal Diagnosis of Rare Genetic conditions at a Tertiary care hospital in Karachi. This is a retrospective review conducted at the Aga Khan University Hospital, Karachi from January 2016 to July 2018. All cases undergoing invasive testing by Chorionic villus sampling for indications other than Thalassemia were included. Forty percent of patients in our cohort underwent invasive testing for muscular dystrophies particularly survival motor neuron (SMN) gene deletion and 32% for Cystic Fibrosis. Other rare disorders like JAM 3 mutation, PEX 1 gene, Barters Syndrome, Wardenberg, Bardet-Beidl Syndrome and Lissencephaly accounted for 28%. Sophistication in laboratory technology and DNA banking has improved the prenatal diagnosis of rare genetic disorders particularly SMN gene deletion. Integrated care involving foetal medicine specialist, Paediatric geneticist, and dedicated Laboratory personnel improves Counseling and Diagnosis of rare genetic conditions. Provision of dedicated nursing staff along with strengthening of welfare facility for non-affording patients would improve the uptake of invasive testing.