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Article ; Online: Like Mother, Like Daughter: Feeding Intolerance in the NICU.

Khattar, Divya / Hopkin, Robert J

NeoReviews

2021 Volume 22, Issue 11, Page(s) e774–e777

MeSH term(s)	Breast Feeding ; Female ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Mothers ; Nuclear Family
Language	English
Publishing date	2021-11-01
Publishing country	United States
Document type	Journal Article
ISSN	1526-9906
ISSN (online)	1526-9906
DOI	10.1542/neo.22-11-e774
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Article ; Online: Phenotypic variability in Joubert syndrome is partially explained by ciliary pathophysiology.

Owens, Joshua W / Hopkin, Robert J / Martin, Lisa J / Kodani, Andrew / Simpson, Brittany N

Annals of human genetics

2023 Volume 88, Issue 1, Page(s) 86–100

Abstract: Introduction: Joubert syndrome (JS) arises from defects of primary cilia resulting in potential malformations of the brain, kidneys, eyes, liver, and limbs. Several of the 35+ genes associated with JS have recognized genotype/phenotype correlations, but ...

Abstract	Introduction: Joubert syndrome (JS) arises from defects of primary cilia resulting in potential malformations of the brain, kidneys, eyes, liver, and limbs. Several of the 35+ genes associated with JS have recognized genotype/phenotype correlations, but most genes have not had enough reported individuals to draw meaningful conclusions. Methods: A PubMed literature review identified 688 individuals with JS across 32 genes and 112 publications to bolster known genotype/phenotype relationships and identify new correlations. All included patients had the "molar tooth sign" and a confirmed genetic diagnosis. Individuals were categorized by age, ethnicity, sex and the presence of developmental disability/intellectual disability, hypotonia, abnormal eye movements, ataxia, visual impairment, renal impairment, polydactyly, and liver abnormalities. Results: Most genes demonstrated unique phenotypic profiles. Grouping proteins based on physiologic interactions established stronger phenotypic relationships that reflect known ciliary pathophysiology. Age-stratified data demonstrated that end-organ disease is progressive in JS. Most genes demonstrated a significant skew towards having variants with either residual protein function or no residual protein function. Conclusion: This cohort demonstrates that clinically meaningful genotype/phenotype relationships exist within most JS-related genes and can be referenced to allow for more personalized clinical care.
MeSH term(s)	Humans ; Abnormalities, Multiple/genetics ; Cerebellum/abnormalities ; Kidney Diseases, Cystic/genetics ; Eye Abnormalities/genetics ; Retina/abnormalities ; Proteins/genetics ; Biological Variation, Population
Chemical Substances	Proteins
Language	English
Publishing date	2023-11-03
Publishing country	England
Document type	Journal Article
ZDB-ID	333-5
ISSN	1469-1809 ; 0003-4800
ISSN (online)	1469-1809
ISSN	0003-4800
DOI	10.1111/ahg.12537
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Article ; Online: Early behavioral and developmental interventions in ADNP-syndrome: A case report of SWI/SNF-related neurodevelopmental syndrome.

Shillington, Amelle / Pedapati, Ernest / Hopkin, Robert / Suhrie, Kristen

Molecular genetics & genomic medicine

2020 Volume 8, Issue 6, Page(s) e1230

Abstract: Background: Autism spectrum disorder (ASD) affects approximately one in 59 children. Variants in the activity-dependent neuroprotector homeobox ADNP (OMIM #611386) gene may be one of the most common single-gene causes of syndromic ASD. Most patients ... ...

Abstract	Background: Autism spectrum disorder (ASD) affects approximately one in 59 children. Variants in the activity-dependent neuroprotector homeobox ADNP (OMIM #611386) gene may be one of the most common single-gene causes of syndromic ASD. Most patients diagnosed with ADNP syndrome have ASD as a comorbidity, and all patients have mild-to-severe intellectual disability. Methods/case report: We present a case report of a patient diagnosed with ADNP syndrome at 2.5 years of age. The patient has many of the key features of the syndrome, including ASD, global developmental delay, behavioral problems, congenital heart defect, early tooth eruption, and vision problems. The patient's initial presentation included congenital diaphragmatic hernia (CDH), which has not been previously reported in this condition. Results: The patient exhibited frequent behavioral outbursts and was initiated on antipsychotic medication with near-complete resolution of symptoms allowing her to engage more fully in early intervention therapies leading to progress in language acquisition. Conclusion: This short report provides guidance for antipsychotic medication dosing to improve early intervention outcomes. This is the first report of CDH in this syndrome.
MeSH term(s)	Antipsychotic Agents/administration & dosage ; Antipsychotic Agents/therapeutic use ; Autism Spectrum Disorder/drug therapy ; Autism Spectrum Disorder/genetics ; Autism Spectrum Disorder/pathology ; Behavioral Symptoms/drug therapy ; Behavioral Symptoms/genetics ; Behavioral Symptoms/pathology ; Child, Preschool ; Early Medical Intervention ; Female ; Hernias, Diaphragmatic, Congenital/drug therapy ; Hernias, Diaphragmatic, Congenital/genetics ; Hernias, Diaphragmatic, Congenital/pathology ; Homeodomain Proteins/genetics ; Humans ; Nerve Tissue Proteins/genetics ; Risperidone/administration & dosage ; Risperidone/therapeutic use ; Syndrome
Chemical Substances	ADNP protein, human ; Antipsychotic Agents ; Homeodomain Proteins ; Nerve Tissue Proteins ; Risperidone (L6UH7ZF8HC)
Language	English
Publishing date	2020-04-10
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2734884-2
ISSN	2324-9269 ; 2324-9269
ISSN (online)	2324-9269
ISSN	2324-9269
DOI	10.1002/mgg3.1230
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Article: A Collaborative Psychiatric-Genetics Inpatient Care Delivery Model Improves Access to Clinical Genetic Evaluation, Testing, and Diagnosis for Patients With Neurodevelopmental Disorders.

Shillington, Amelle / Lamy, Martine / Dominick, Kelli C / Sorter, Michael / Erickson, Craig A / Hopkin, Robert

Frontiers in genetics

2022 Volume 13, Page(s) 901458

Abstract: Neurodevelopmental disorders including autism spectrum disorder, intellectual disability, and global developmental delay are among the most common indications for referral to clinical genetics evaluation; and clinical genetic testing is indicated for ... ...

Abstract	Neurodevelopmental disorders including autism spectrum disorder, intellectual disability, and global developmental delay are among the most common indications for referral to clinical genetics evaluation; and clinical genetic testing is indicated for people with neurodevelopmental disorders. There are known barriers to care in accessing clinical genetics evaluation for this patient population. We created a collaborative psychiatric-genetics consultation service and psychiatric-genetics outpatient clinic with the goal to improve care delivery to patients with neurodevelopmental disorders. Two years after the launch of this pilot program, our data demonstrate improved access to genetics evaluation with shorter wait times and fewer patients lost to follow-up. Perhaps most importantly, new genetic diagnoses changed medical care for the majority of patients.
Language	English
Publishing date	2022-06-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606823-0
ISSN	1664-8021
ISSN	1664-8021
DOI	10.3389/fgene.2022.901458
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Article ; Online: Prenatal and infantile diagnosis of craniosynostosis in individuals with RASopathies.

Serbinski, Carolyn R / Vanderwal, April / Chadwell, Sarah E / Sanchez, Ana Isabel / Hopkin, Robert J / Hufnagel, Robert B / Weaver, K Nicole / Prada, Carlos E

American journal of medical genetics. Part A

2023 Volume 194, Issue 2, Page(s) 195–202

Abstract: Fetuses with RASopathies can have a wide variety of anomalies including increased nuchal translucency, hydrops fetalis, and structural anomalies (typically cardiac and renal). There are few reports that describe prenatal-onset craniosynostosis in ... ...

Abstract	Fetuses with RASopathies can have a wide variety of anomalies including increased nuchal translucency, hydrops fetalis, and structural anomalies (typically cardiac and renal). There are few reports that describe prenatal-onset craniosynostosis in association with a RASopathy diagnosis. We present clinical and molecular characteristics of five individuals with RASopathy and craniosynostosis. Two were diagnosed with craniosynostosis prenatally, 1 was diagnosed as a neonate, and 2 had evidence of craniosynostosis noted as neonates without formal diagnosis until later. Two of these individuals have Noonan syndrome (PTPN11 and KRAS variants) and three individuals have Cardiofaciocutaneous syndrome (KRAS variants). Three individuals had single suture synostosis and two had multiple suture involvement. The most common sutures involved were sagittal (n = 3), followed by coronal (n = 3), and lambdoid (n = 2) sutures. This case series confirms craniosynostosis as one of the prenatal findings in individuals with RASopathies and emphasizes the importance of considering a RASopathy diagnosis in fetuses with multiple anomalies in combination with craniosynostosis.
MeSH term(s)	Infant, Newborn ; Female ; Humans ; Pregnancy ; Proto-Oncogene Proteins p21(ras)/genetics ; Craniosynostoses/diagnosis ; Craniosynostoses/genetics ; Heart Defects, Congenital ; Noonan Syndrome/diagnosis ; Noonan Syndrome/genetics ; Ultrasonography, Prenatal
Chemical Substances	Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2023-09-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2108614-X
ISSN	1552-4833 ; 0148-7299 ; 1552-4825
ISSN (online)	1552-4833
ISSN	0148-7299 ; 1552-4825
DOI	10.1002/ajmg.a.63397
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Zs.A 1376/A: Show issues

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Article ; Online: RNA sequencing reveals a complete picture of a homozygous missense variant in a patient with VPS13D movement disorder: a case report and review of the literature.

Baker, Elizabeth K / Han, Jingfen / Langley, William A / Reott, Michael A / Hallinan, Barbara E / Hopkin, Robert J / Zhang, Wenying

Molecular genetics and genomics : MGG

2023 Volume 298, Issue 5, Page(s) 1185–1199

Abstract: RNA sequencing (RNA-seq) is a complementary diagnostic tool to exome sequencing (ES), only recently clinically available to undiagnosed patients post-ES, that provides functional information on variants of unknown significance (VUS) by evaluating its ... ...

Abstract	RNA sequencing (RNA-seq) is a complementary diagnostic tool to exome sequencing (ES), only recently clinically available to undiagnosed patients post-ES, that provides functional information on variants of unknown significance (VUS) by evaluating its effect on RNA transcription. ES became clinically available in the early 2010s and promised an agnostic platform for patients with a neurological disease, especially for those who believed to have a genetic etiology. However, the massive data generated by ES pose challenges in variant interpretation, especially for rare missense, synonymous, and deep intronic variants that may have a splicing effect. Without functional study and/or family segregation analysis, these rare variants would be likely interpreted as VUS which is difficult for clinicians to use in clinical care. Clinicians are able to assess the VUS for phenotypic overlap, but this additional information alone is usually not enough to re-classify a variant. Here, we report a case of a 14-month-old male who presented to clinic with a history of seizures, nystagmus, cerebral palsy, oral aversion, global developmental delay, and poor weight gain requiring gastric tube placement. ES revealed a previously unreported homozygous missense VUS, c.7406A > G p.(Asn2469Ser), in VPS13D. This variant has not been previously reported in genome aggregation database (gnomAD), ClinVar, or in any peer-reviewed published literature. By RNA-seq, we demonstrated that this variant mainly impacts splicing and results in a frameshift and early termination. It is expected to generate either a truncated protein, p.(Val2468fs*19), or no protein from this transcript due to nonsense-mediated mRNA decay leading to VPS13D deficiency. To our knowledge, this is the first case utilizing RNA-seq to further functionally characterize a homozygous novel missense VUS in VPS13D and confirm its impact on splicing. This confirmed pathogenicity gave the diagnosis of VPS13D movement disorder to this patient. Therefore, clinicians should consider utilizing RNA-seq to clarify VUS by evaluating its effect on RNA transcription.
MeSH term(s)	Humans ; Male ; Infant ; Exome Sequencing ; Mutation ; RNA ; Movement Disorders ; Sequence Analysis, RNA ; Proteins
Chemical Substances	RNA (63231-63-0) ; VPS13D protein, human ; Proteins
Language	English
Publishing date	2023-06-20
Publishing country	Germany
Document type	Review ; Case Reports ; Journal Article
ZDB-ID	2044817-X
ISSN	1617-4623 ; 1617-4615
ISSN (online)	1617-4623
ISSN	1617-4615
DOI	10.1007/s00438-023-02044-y
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Zs.A 1198: Show issues

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Article ; Online: Development of the Fabry Disease Patient-Reported Outcome (FD-PRO): a new instrument to measure the symptoms and impacts of Fabry Disease.

Hamed, Alaa / DasMahapatra, Pronabesh / Lyn, Nicole / Gwaltney, Chad / Hopkin, Robert J

Orphanet journal of rare diseases

2021 Volume 16, Issue 1, Page(s) 285

Abstract: Background: The systematic collection of disease-specific symptoms and impacts on the lives of patients with Fabry Disease (FD) can offer unique insights into the patient experience, yet no disease-specific tool to measure FD symptoms exists. This study ...

Abstract	Background: The systematic collection of disease-specific symptoms and impacts on the lives of patients with Fabry Disease (FD) can offer unique insights into the patient experience, yet no disease-specific tool to measure FD symptoms exists. This study describes the development of the Fabry Disease Patient-Reported Outcome (FD-PRO). Methods: A targeted literature search, interviews with key opinion leaders (KOLs), and concept elicitation (CE) interviews with patients identified the most frequent signs and symptoms associated with FD and their impact on daily life. Cognitive interviews evaluated patients' ability to understand the FD-PRO instructions and respond to the items on the draft FD-PRO instrument. Results: The targeted literature search identified key signs and symptoms in domains that were confirmed in KOL interviews. In CE interviews with 37 treated and treatment-naïve patients, neuropathic pain symptoms (95% treated, 82% treatment-naïve), temperature intolerance (95% treated, 88% treatment-naïve), energy difficulties (95% treated, 94% treatment-naïve), hearing/vision impairment (95% treated, 71% treatment-naïve), and gastrointestinal symptoms (80% treated, 59% treatment-naïve) were most frequently mentioned. Results were similar for men and women in both treated and treatment-naïve groups. While treatment-naïve patients in general expressed fewer and milder symptoms compared to treated patients, the overall sets of symptoms expressed by the two groups were similar. The most severe symptoms were neuropathic pain, stomach pain, burning pain, and fatigue. The most bothersome symptoms were stomach pain, breathing difficulty, fatigue, neuropathic pain, and constipation. The most frequent impacts were in the work/school limitations domain for both treated and treatment-naïve patients. The impacts with the highest difficulty ratings were stress, limited outdoor activity, and guilt. Cognitive interviews with 14 treated and treatment-naïve patients resulted in the refinement of FD-PRO items and language. Conclusions: The FD-PRO is a novel, disease-specific instrument that measures the patient experience in Fabry disease. Such tools are valuable in capturing the burden of disease in patients with FD and demonstrating the value of treatment in clinical trials.
MeSH term(s)	Fabry Disease ; Fatigue ; Female ; Humans ; Male ; Patient Reported Outcome Measures ; Surveys and Questionnaires
Language	English
Publishing date	2021-06-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2225857-7
ISSN	1750-1172 ; 1750-1172
ISSN (online)	1750-1172
ISSN	1750-1172
DOI	10.1186/s13023-021-01894-2
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Article ; Online: Arrhythmia Burden and Heart Rate Response During Exercise in Anderson-Fabry Disease.

Powell, Adam W / Wittekind, Samuel G / Mays, Wayne A / Lang, Sean M / Knilans, Timothy K / Prada, Carlos E / Hopkin, Robert J / Chin, Clifford

Texas Heart Institute journal

2022 Volume 49, Issue 5

Abstract: Patients with Anderson-Fabry disease (AFD) have an elevated incidence of resting arrhythmias and ischemic heart disease, but their exercise arrhythmia burden and ischemic changes are not well understood. In addition, little research has been done on ... ...

Abstract	Patients with Anderson-Fabry disease (AFD) have an elevated incidence of resting arrhythmias and ischemic heart disease, but their exercise arrhythmia burden and ischemic changes are not well understood. In addition, little research has been done on heart rate recovery in these patients. We retrospectively reviewed charts of patients with AFD who underwent maximal effort cardiopulmonary exercise testing (CPET) (n=44; 38.2 ± 13.8 yr; 23 men) from 2012 through 2018. Electrocardiographic, Holter monitoring, echocardiographic, cardiac magnetic resonance imaging, and patient demographic data were collected. No patient had adverse events that necessitated CPET termination, whereas 25 (57%) had ectopy during CPET, including 3 (7%) with frequent premature atrial contractions and 5 (11%) with frequent premature ventricular contractions. The ectopic burden was higher during resting electrocardiographic monitoring before exercise. In addition, 7 patients (16%) had pathologic ST-segment or T-wave changes on CPET, defined as ST-segment changes ≥2 mm. Among the patients who had concurrent cardiac magnetic resonance findings with their CPET (n=27), ST-segment or T-wave changes were associated with left ventricular myocardial mass (r=0.43, P=0.02). Chronotropic incompetence was seen during CPET in 28 patients (64%); however, only 2 patients (4%) had abnormal heart rate recovery at 1 minute. This study shows that patients with AFD can safely undergo exercise testing but have a high incidence of exercise-induced arrhythmias and ischemic changes. Ischemic electrocardiographic changes during exercise testing are associated with myocardial mass. Despite the chronotropic incompetence associated with AFD, heart rate recovery appears to be generally preserved in these patients.
MeSH term(s)	Exercise Test/methods ; Fabry Disease ; Heart Rate/physiology ; Humans ; Male ; Retrospective Studies ; Ventricular Premature Complexes/diagnosis ; Ventricular Premature Complexes/etiology
Language	English
Publishing date	2022-11-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	604761-0
ISSN	1526-6702 ; 0730-2347
ISSN (online)	1526-6702
ISSN	0730-2347
DOI	10.14503/THIJ-20-7363
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Zs.A 1452: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A novel pathogenic variant in OFD1 results in X-linked Joubert syndrome with orofaciodigital features and pituitary aplasia.

Aljeaid, Deema / Lombardo, Rachel C / Witte, David P / Hopkin, Robert J

American journal of medical genetics. Part A

2019 Volume 179, Issue 6, Page(s) 1010–1014

Abstract: Orofaciodigital syndrome type I and X-linked recessive Joubert syndrome are known ciliopathic disorders that are caused by pathogenic variants in OFD1 gene. Endocrine system involvement with these conditions is not well described. We present the first ... ...

Abstract	Orofaciodigital syndrome type I and X-linked recessive Joubert syndrome are known ciliopathic disorders that are caused by pathogenic variants in OFD1 gene. Endocrine system involvement with these conditions is not well described. We present the first report of a newborn male with a novel hemizygous variant in OFD1 gene c.515T>C, (p.Leu172Pro) resulting in X-linked Joubert syndrome and orofaciodigital features with complete pituitary gland aplasia and subsequent severe hypoplasia of peripheral endocrine glands. This clinical report expands the phenotypic spectrum of endocrine system involvement in OFD1-related disorders and suggests that OFD1 gene may be related to pituitary gland development.
MeSH term(s)	Abnormalities, Multiple/diagnosis ; Abnormalities, Multiple/genetics ; Alleles ; Cerebellum/abnormalities ; Eye Abnormalities/diagnosis ; Eye Abnormalities/genetics ; Genes, X-Linked ; Genotype ; Humans ; Infant, Newborn ; Kidney Diseases, Cystic/diagnosis ; Kidney Diseases, Cystic/genetics ; Magnetic Resonance Imaging ; Male ; Mutation ; Orofaciodigital Syndromes/diagnosis ; Orofaciodigital Syndromes/genetics ; Pedigree ; Phenotype ; Pituitary Gland/abnormalities ; Proteins/genetics ; Radiography ; Retina/abnormalities ; Whole Exome Sequencing
Chemical Substances	OFD1 protein, human ; Proteins
Language	English
Publishing date	2019-03-20
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	1493479-6
ISSN	1552-4833 ; 1552-4825
ISSN (online)	1552-4833
ISSN	1552-4825
DOI	10.1002/ajmg.a.61018
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Article ; Online: Fetal Magnetic Resonance Imaging (MRI) in Holoprosencephaly and Associations With Clinical Outcome: Implications for Fetal Counseling.

Riddle, Artur / Nagaraj, Usha / Hopkin, Robert J / Kline-Fath, Beth / Venkatesan, Charu

Journal of child neurology

2020 Volume 36, Issue 5, Page(s) 357–364

Abstract: Holoprosencephaly is the most common malformation of forebrain development and includes a wide spectrum of severity. The objective of this retrospective study was to evaluate fetal magnetic resonance imaging (MRI) associations with outcome. Of the 63 ... ...

Abstract	Holoprosencephaly is the most common malformation of forebrain development and includes a wide spectrum of severity. The objective of this retrospective study was to evaluate fetal magnetic resonance imaging (MRI) associations with outcome. Of the 63 cases identified on antenatal ultrasonography, 28 cases were confirmed on fetal MRI. There were 17 live births; 9 patients died within the first month of life. There were 7 survivors. The vast majority were nonambulatory and required feeding support; none required respiratory support. We found that presence and number of non-holoprosencephaly-associated malformations was also associated with survival. Of 5 patients with 3 or more systemic anomalies, 4 died regardless of holoprosencephaly subtype and 1 was lost to follow-up. Patients with suspected holoprosencephaly on ultrasonography should have full body fetal MRI and echocardiogram to better evaluate systemic anomalies. Counseling should involve pediatric palliative care services to prepare families in caring for babies with limited life span.
MeSH term(s)	Adult ; Brain/diagnostic imaging ; Child, Preschool ; Counseling/methods ; Female ; Holoprosencephaly/diagnostic imaging ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging/methods ; Pregnancy ; Prenatal Diagnosis/methods ; Retrospective Studies
Language	English
Publishing date	2020-11-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	639288-x
ISSN	1708-8283 ; 0883-0738
ISSN (online)	1708-8283
ISSN	0883-0738
DOI	10.1177/0883073820972290
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