Objectives
Parents receiving a prenatal diagnosis of alobar holoprosencephaly (HPE) often experience uncertainty regarding the pregnancy prognosis. There is little known about how best to counsel and ...support families receiving the diagnosis. This study explored parental experiences and wishes after receiving a prenatal diagnosis of alobar HPE.
Methods
This was a retrospective qualitative study. Semi‐structured interviews were conducted to determine factors impacting parents' decision‐making process, experiences with healthcare providers, and expectations for their child's length and quality of life. Interviews were analyzed using qualitative content analysis.
Results
Eight mothers who received a prenatal diagnosis of alobar HPE between 2013 and 2019 participated in the study. Parental expectations were based on information conveyed during prenatal counseling. Religious and personal beliefs, perceived suffering, and provider prognostication contributed to parent decisions and goals of care. Participants reported pressure to terminate the pregnancy. Parents were not prepared for the possibility of survival beyond the perinatal period. Most parents reported no regret in their choices.
Conclusion
Patients receiving a prenatal diagnosis of alobar HPE desire access to balanced prenatal counseling about prognosis, morbidity, and mortality. Providers should explore values and beliefs that contribute to parents' goals of care and offer appropriate information and referrals.
Key points
What's already known about this topic?
Prior studies of all types of holoprosencephaly (HPE) have shown that families are unprepared for the infant to survive delivery, and frequently have traumatic experiences during prenatal counseling. These studies were mainly done 10–20 years ago.
What does this study add?
Parents who receive a prenatal diagnosis of alobar HPE desire comprehensive holistic prenatal counseling about perinatal prognosis and support in navigating goals of care. They want providers to be realistic but also acknowledge uncertainties, and if unfamiliar with the condition refer to providers who are knowledgeable. Our study shows that in the past 20 years families do not feel the quality of fetal counseling for this condition has improved.
Improved fetal imaging has resulted in increased diagnosis of isolated absent septum pellucidum without other intracranial abnormalities. There is little literature regarding outcomes for these ...fetuses. This study hypothesized the majority of infants diagnosed by fetal magnetic resonance imaging (MRI) with isolated absent septum pellucidum would retain this diagnosis postnatally. Specifically, in the absence of postnatal endocrine or ophthalmologic abnormalities, postnatal imaging would find no additional related findings, and fetuses would be at low risk for developmental delay. Two of 8 subjects met postnatal criteria for septo-optic dysplasia; remaining subjects had normal postnatal endocrine and ophthalmologic evaluations and no significant related findings on postnatal MRI. One subject without septo-optic dysplasia had delays on developmental screening; all others had normal screening (range of follow-up 8-72 months). Our study questions the necessity of postnatal imaging for prenatally diagnosed isolated absent septum pellucidum. Majority of fetuses with isolated absent septum pellucidum retained this diagnosis postnatally.
ACOX1 (acyl-CoA oxidase 1) encodes the first and rate-limiting enzyme of the very-long-chain fatty acid (VLCFA) β-oxidation pathway in peroxisomes and leads to H2O2 production. Unexpectedly, ...Drosophila (d) ACOX1 is mostly expressed and required in glia, and loss of ACOX1 leads to developmental delay, pupal death, reduced lifespan, impaired synaptic transmission, and glial and axonal loss. Patients who carry a previously unidentified, de novo, dominant variant in ACOX1 (p.N237S) also exhibit glial loss. However, this mutation causes increased levels of ACOX1 protein and function resulting in elevated levels of reactive oxygen species in glia in flies and murine Schwann cells. ACOX1 (p.N237S) patients exhibit a severe loss of Schwann cells and neurons. However, treatment of flies and primary Schwann cells with an antioxidant suppressed the p.N237S-induced neurodegeneration. In summary, both loss and gain of ACOX1 lead to glial and neuronal loss, but different mechanisms are at play and require different treatments.
Display omitted
•Loss of dACOX1 leads to glial degeneration via accumulation of VLCFA•A de novo ACOX1N237S gain-of-function mutation also leads to glial loss•Glial loss in ACOX1N237S is associated with elevated ROS, not an increase in VLCFA•N-acetyl cysteine amide, an antioxidant, suppresses glial defects in ACOX1N237S flies
Chung et al. show that ACOX1, a peroxisomal protein required for degrading VLCFA, is mostly expressed in glial cells. Its loss causes an accumulation of VLCFA and glial loss. An ACOX1 gain-of-function mutation identified in three individuals leads to elevated ROS and glial loss and is potently suppressed by antioxidants.
Congenital hypomyelinating neuropathy is a rare form of hereditary peripheral neuropathy characterized by nonprogressive weakness, areflexia, hypotonia, severely reduced nerve conduction velocities, ...and hypomyelination. Mutations in contactin-associated protein 1 (CNTNAP1) were recently described as a cause of congenital hypomyelinating neuropathy. CNTNAP1-associated congenital hypomyelinating neuropathy is characterized by severe hypotonia, multiple distal joint contractures, and high mortality in the first few months of life.
Whole-exome sequencing was performed in two siblings with congenital hypotonia. Detailed phenotyping data were compared with previously reported cases.
A novel, heterozygous compound mutation of CNTNAP1 was identified in both siblings. We also reviewed 17 patients harboring 10 distinct mutations from previously published studies. All patients presented with severe hypotonia, respiratory distress, and multiple cranial nerve palsies at birth. Six of 19 patients survived beyond infancy and required chronic mechanical ventilation. Seizures were common in the surviving patients.
These findings suggest that CNTNAP1-related congenital hypomyelinating neuropathy is a distinct form of hereditary neuropathy that affects both the central and peripheral nervous systems with no clear phenotype-genotype correlation. Our findings also indicate that arthrogryposis multiplex congenita and early lethality are not universal outcomes for patients with congenital hypomyelinating neuropathy.
A female infant was delivered via cesarean section at 39 weeks' gestation to a 40-year-old mother. Pregnancy was notable for normal fetal movement and amniotic fluid indices. Apgar scores were 7 and ...8 at 1 and 5 minutes. Shortly after birth, the infant developed respiratory distress and apnea that resolved with repositioning of her neck and trunk. General examination was remarkable for severe micrognathia, high arched palate, bitemporal wasting, and bilateral talipes varus (club foot) contractures.
Proteus syndrome is a mosaic genetic overgrowth disorder caused by a postzygotic, mosaic activating mutation in AKT1. Rare prenatal presentations include segmental tissue overgrowth, and skeletal and ...CNS anomalies. We present the first report of prenatally diagnosed and molecularly confirmed Proteus syndrome. Prenatal imaging identified megalencephaly, brain and eye malformations, focal soft tissue enlargement, and ambiguous genitalia. Exome sequencing performed on cultured amniocytes demonstrated an AKT1 pathogenic variant consistent with Proteus syndrome, and postnatal examination confirmed the diagnosis. Postnatal Sanger sequencing could not identify the AKT1 pathogenic variant. This case underscores the importance of prenatal exome sequencing on cultured amniocytes for mosaic overgrowth disorders, as well as provides additional information on the prenatal phenotype of Proteus syndrome, and highlights the impact of prenatal diagnosis on postnatal management.
Muslims comprise nearly a quarter of the worldwide population, with significant populations in the United States, Canada, and Europe. As clinicians, it is important to be familiar with Islamic ...religious and cultural perspectives on medical treatment, life-prolonging measures and comfort and palliative care, but historically, this has been a gap in the literature. Recently, there have been multiple papers discussing Islamic bioethics, particularly in regards to end of life care in adults; however, there has been a lack of literature discussing the Islamic perspective on issues related to neonatal and perinatal end of life care. This paper uses clinical scenarios to review key relevant principles of Islamic law, discussing the primary and secondary sources used in formulating
including the Quran,
,
and '
, and the importance of preservation of life and upholding of human dignity (
). Neonatal and perinatal scenarios are used to specifically explore the Islamic perspective on withholding and withdrawal of life-sustaining measures and determining what constitutes an acceptable quality of life. In some Islamic cultures the expertise of the patient's physician is given significant weight in making these judgments, and as such, families may appreciate frank assessment of the situation by the clinical team. Because of the various factors involved in issuing religious ruling, or
, there is a wide spectrum of opinions on these rulings, and physicians should be aware of these differences, seek counsel and guidance from local Islamic leaders, and support families in their decision-making process.
Fetal neurology is a rapidly evolving and expanding field. Discussions about diagnosis, prognosis, treatment options, and goals of care often begin in the antenatal period. However, there are ...inherent challenges to fetal counseling of neurological diagnoses due to limitations of fetal imaging, prognostic uncertainty, and variability in neurodevelopmental outcomes. In the midst of uncertainty, families are challenged with preparing a care plan for their baby while simultaneously experiencing profound grief. The paradigms of perinatal palliative care can assist with the grieving process and help frame diagnostic testing and complex decision-making within the context of a family's spiritual, cultural, and social belief system. This ultimately leads to a shared decision-making process and value driven medical care. While perinatal palliative care programs have expanded, many families faced with such diagnoses never meet with a palliative care team prior to delivery. Moreover, there is significant variability in the availability of palliative care services throughout the country. Using an illustrative vignette of a patient with a prenatally diagnosed encephalocele, this review aims to provide a basic framework of perinatal palliative care for fetal neurology diagnoses that emphasizes 1) importance of clear, consistent, and transparent communication among all subspecialists and families, 2) creation of a palliative care birth plan, 3) importance of consistent care providers and longitudinal points of contact prenatally and post-delivery, 4) close communication between the prenatal and post-natal providers to allow for optimal continuity of care, and 5) recognize that information, care plans, and goals of care often evolve over time.
PDF
