Publications

Scholarly Journals--Accepted

  • "ANKLE2-related microcephaly: a variable microcephaly syndrome resembling Zika infection" has been accepted for publication in Annals of Clinical and Translational Neurology.  (06/2022)

Online Publications

  • 50th Genetics Corner: A Patient with CHARGE Syndrome Illustrates the Parable of the Six Blind Men and the Elephant. Ashleigh Hansen, Robin D. Clark. Neonatology Today. June 2022, 142-144 (06/2022) (link)
  • Genetics Corner: Klippel-Trenaunay Syndrome in an Infant with a Mosaic PIK3CA Variant, a Target for the Medical Treatment of Asymmetric Overgrowth. Robin D. Clark, Subhadra Ramanathan. Neonatology Today May 2022,145-148. (05/2022) (link)
  • Genetics Corner: Syndromic Etiology of Apparently Isolated Clubfeet: a Child with Loeys-Dietz Syndrome. Subhadra Ramanathan, Robin Dawn Clark. Neonatology Today April 2022, 127-132 (04/2022) (link)
  • Genetics Corner: Donohue Syndrome in a Small for Gestational Age Infant with Hyperinsulinemia. Jonathan Tam, Tiffany Chan, Herbert Vasquez, Robin D. Clark. Neonatology Today, March 2022, 146-150 (03/2022) (link)
  • Genetics Corner: Alpha Thalassemia X-Linked Intellectual Disability Syndrome in an Infant with Developmental Delay and DYS Recurrent Respiratory Failure Confirmed by Whole-Exome Sequencing. Carolina Olavarry, Jason W. Tate, Ashleigh Hansen, Hua Wang, Robin D. Clark. Neonatology Today February 2022, 131-135. (02/2022) (link)
  • Genetics Corner: “Coat-hanger” ribs and Bell-Shaped Thorax in an Infant with Paternal Uniparental Disomy for Chromosome 14. Subhadra Ramanathan, Robin Dawn Clark. Neonatology Today Jan 2022, 130-134. (01/2022) (link)
  • Genetics Corner: Cat-Eye-Syndrome and Genetic Syndromes Associated with Ear Anomalies. Subhadra Ramanathan, Robin Dawn Clark. Neonatology Today. December 2021, 128-132. (12/2021) (link)
  • Genetics Corner: A Newborn with a Disorder of Sex Development Caused by  45,X/46,X,idic(Y) Mosaicism. Robin Dawn Clark. Neonatology Today. November 2021, 133-136. (11/2021) (link)
  • Atypical Williams Syndrome in a Child who Presented with Aortic Stenosis and Coarctation and a Positive Family History. Ashleigh Hansen, Lily Radanovich, Robin Dawn Clark. Neonatology Today. October 2021, 134-138. (10/2021) (link)
  • Genetic Corner: Diaphragmatic Hernia in an Infant with a Type II Distal Deletion of 22q11.2 (LCR22E-F). Robin Dawn Clark. Neonatology Today. September 2021, 131-133. (09/2021) (link)
  • The Genetics Corner: A Mother and Child with Cleft lip and Palate Have an Atypical 1p36 Deletion that Disrupts KIF1B, a Cause of Autosomal Dominant Charcot-Marie-Tooth Disease, Type 2A1. Subhadra Ramanathan, Robin Dawn Clark. Neonatology Today. August 2021, 118-121. (08/2021) (link)
  • The Genetics Corner: A Preterm Infant with Down Syndrome Complicated by Severe Transient Abnormal Myelopoiesis. Robin Dawn Clark. Neonatology Today. July 2021, 124-125. (07/2021) (link)
  • Genetics Corner: Multisuture Craniosynostosis Secondary to Intrauterine Constraint During Gestation in a Bicornuate Uterus. Robin Dawn Clark, Subhadra Ramanathan. Neonatology Today. June 2021, 131-133. (06/2021) (link)
  • Ramanathan S, Wood M, Clark R. The Genetics Corner: A consultation for neonatal diabetes mellitus reveals uniparental disomy 6. Neonatology Today. 2020 May;15(5):82-84. www.neonatologytoday.net (05/2020)
  • Clark R, Ramanathan S. The Genetics Corner: Perisylvian polymicrogyria and seizures in one of monochorionic diamniotic twins following Twin-Twin-Transfusion syndrome following in utero laser ablation therapy. Neonatology Today. 2020 Apr;15(4):71-74. www.neonatologytoday.net (04/2020)
  • Clark R, Ramanathan S, Hernandez D. Genetics Corner: A lethal ciliopathy affects two siblings with renal dysplasia and oligohydramnios. Neonatology Today. 2020 Mar;15(3):66-69. www.neonatologytoday.net (03/2020)
  • Clark R. Genetics Corner: Alveolar simplification and Down syndrome. Neonatology Today. 2020 Feb;15(2):70-72. www.neonatologytoday.net (02/2020)
  • Clark R. Genetics Corner: Prenatal diagnosis of Klinefelter syndrome. Neonatology Today. 2020 Jan;15(1):65-66. www.neonatologytoday.net (01/2020)
  • Clark R, Rajakumar N. Genetics Corner: Genetic counseling and family screening after prenatal diagnosis of hypoplastic left heart syndrome: Is it warranted? Neonatology Today.  2019 Dec;14(12):86-87. www.neonatologytoday.net (12/2019)
  • Hernandez D, Ramanathan S, Clark R.  Genetics Corner: A consultation for Wolf-Hirschhorn syndrome.  Neonatology Today. 2019 Nov;14(11):79-82.   www.neonatologytoday.net. (11/2019)
  • Hernandez D, Ramanathan S, Clark R.  Genetics Corner: Translocation Down syndrome.  Neonatology Today. 2019 Oct;14(10):72-74.   www.neonatologytoday.net (10/2019)
  • Clark R, Hernandez D, Ramanathan S. Genetics Corner: Down syndrome tool-skit – A resource for physicians taking care of neonates.  Neonatology Today. 2019 Sep;14(9):83-87.   www.neonatologytoday.net (09/2019)
  • Clark R. Frequently Asked Questions, Part II: More about copy number variants (CNVs), variants of uncertain significance (VUS) in chromosome microarrays, with a special focus on congenital heart defects (CHDs). Neonatology Today. 2019 Aug;14(8):67-68. www.neonatologytoday.net (08/2019)
  • Clark R. The Genetics Corner: Frequently Asked Questions, Part I: About copy number variants (CNV), variants of uncertain significance (VUS) in chromosome microarrays (CMA). Neonatology Today. 2019 July;14(7):64-66.   www.neonatologytoday.net (07/2019)
  • Clark R. The Genetics Corner: A genetics consultation for a family history of permanent neonatal-onset diabetes mellitus. Neonatology Today.  2019 June;14(6):78-79. www.neonatologytoday.net (06/2019)
  • Ramanathan S, Clark R. The Genetics Corner: A genetics consultation for multiple congenital anomalies.  Neonatology Today. 2019 May;14(5):75-79.   www.neonatologytoday.net (05/2019)
  • Ramanathan S, Clark R. The Genetics Corner: A genetics consultation for agenesis cutis congenita and methimazole exposure.  Neonatology Today. 2019 Apr;14(4):57-59.   www.neonatologytoday.net (04/2019)
  • Ramanathan S, Clark R. The Genetics Corner: A genetics consultation for chronic diarrhea that revealed incest. Neonatology Today. 2019 Mar;14(3):67-8.   www.neonatologytoday.net (03/2019)
  • Clark R, Ramanathan S. The Genetics Corner: A genetics consultation for agenesis of the corpus callosum and poor feeding.  Neonatology Today. 2019 Feb;14(2):59-61. www.neonatologytoday.net (02/2019)
  • Clark R, Ramanathan S. The Genetics Corner: A genetics consultation for congenital syphylis.  Neonatology Today. 2019 Jan;14(1):61-63.   www.neonatologytoday.net (01/2019)
  • Clark R, Ramanathan S. The Genetics Corner: A genetics consultation for heterotaxy.  Neonatology Today. 2018 Dec;13(12):62-63.   www.neonatologytoday.net (12/2018)
  • Clark R, Ramanathan S. A genetics consultation for multiple congenital dislocations.  Neonatology Today. 2018 Nov;13(11):57-59.   www.neonatologytoday.net (11/2018)
  • Ramanathan S, Clark R. The Genetics Corner: A consultation for family history of hearing loss.  Neonatology Today. 2018 Oct;13(10):49-51.   www.neonatologytoday.net (10/2018)
  • Ramanathan S, Clark R. The Genetics Corner: A consultation for microtia, ASD and IUGR. Neonatology Today. 2018 Sept;13(9):59-60. www.neonatologytoday.net (09/2018)
  • Clark R. The Genetics Corner: A consultation for omphalocele. Neonatology Today. 2018 Aug;13(8):42-43. www.neonatologytoday.net (08/2018)
  • Ramanathan S, Marchosky R, Clark R. The Genetics Corner: A consultation for orofacial cleft: van der Woude syndrome.  Neonatology Today. 2018 July;13(7):46-47.   www.neonatologytoday.net (07/2018)
  • Ramanathan S, Clark R. The Genetics Corner: A consultation for metopic craniosynostosis and skeletal anomalies.Neonatology Today. 2018 June;13(6):48-50.   www.neonatologytoday.net (06/2018)

Scholarly Journals--Published

  • Omorodion J, Dowsett L, Clark RD, Fraser J, Abu-El-Haija A, Strong A, Wojcik MH, Bryant AS, Gold NB. Delayed diagnosis and racial bias in children with genetic conditions. Am J Med Genet A. 2022 Apr;188(4):1118-1123. doi: 10.1002/ajmg.a.62626. Epub 2022 Jan 17. PMID: 35037400. Abstract As more therapeutics for genetic conditions become available, the need for timely and equitable genetic diagnosis has become urgent. Using clinical cases, we consider the health system-, provider-, and patient-level factors that contribute to the delayed diagnosis of genetic conditions in pediatric patients from minority populations, leading to health disparities between racial groups. We then provide suggestions to address these factors, with the aim of improving minority health and access to genetic care for all children. (04/2022) (link)
  • Yabumoto M, Kianmahd J, Singh M, Palafox MF, Wei A, Elliott K, Goodloe DH, Dean SJ, Gooch C, Murray BK, Swartz E, Schrier Vergano SA, Towne MC, Nugent K, Roeder ER, Kresge C, Pletcher BA, Grand K, Graham JM Jr, Gates R, Gomez-Ospina N, Ramanathan S, Clark RD, Glaser K, Benke PJ, Cohen JS, Fatemi A, Mu W, Baranano KW, Madden JA, Gubbels CS, Yu TW, Agrawal PB, Chambers MK, Phornphutkul C, Pugh JA, Tauber KA, Azova S, Smith JR, O'Donnell-Luria A, Medsker H, Srivastava S, Krakow D, Schweitzer DN, Arboleda VA. Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms. Mol Genet Genomic Med. 2021 Oct;9(10):e1809. doi: 10.1002/mgg3.1809. Epub 2021 Sep 14. PMID: 34519438; PMCID: PMC8580094. Abstract The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B-related disorders. (10/2021) (link)
  • Palmer EE, Whitton C, Hashem MO, Clark RD, Ramanathan S, Starr LJ, Velasco D, De Dios JK, Singh E, Cormier-Daire V, Chopra M, Rodan LH, Nellaker C, Lakhani S, Mallack EJ, Panzer K, Sidhu A, Wentzensen IM, Lacombe D, Michaud V, Alkuraya FS. CHEDDA syndrome is an underrecognized neurodevelopmental disorder with a highly restricted ATN1 mutation spectrum. Clin Genet. 2021 Oct;100(4):468-477. doi: 10.1111/cge.14022. Epub 2021 Jul 13. PMID: 34212383 Abstract We describe the clinical features of nine unrelated individuals with rare de novo missense or in-frame deletions/duplications within the "HX motif" of exon 7 of ATN1. We previously proposed that individuals with such variants should be considered as being affected by the syndromic condition of congenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA), distinct from dentatorubral-pallidoluysian atrophy (DRPLA) secondary to expansion variants in exon 5 of ATN1. We confirm that the universal phenotypic features of CHEDDA are distinctive facial features and global developmental delay. Infantile hypotonia and minor hand and feet differences are common and can present as arthrogryposis. Common comorbidities include severe feeding difficulties, often requiring gastrostomy support, as well as visual and hearing impairments. Epilepsy and congenital malformations of the brain, heart, and genitourinary systems are frequent but not universal. Our study confirms the clinical entity of CHEDDA secondary to a mutational signature restricted to exon 7 of ATN1. We propose a clinical schedule for assessment upon diagnosis, surveillance, and early intervention including the potential of neuroimaging for prognostication. (07/2021) (link)
  • Biesecker LG, Adam MP, Alkuraya FS, Amemiya AR, Bamshad MJ, Beck AE, Bennett JT, Bird LM, Carey JC, Chung B, Clark RD, Cox TC, Curry C, Dinulos MBP, Dobyns WB, Giampietro PF, Girisha KM, Glass IA, Graham JM Jr, Gripp KW, Haldeman-Englert CR, Hall BD, Innes AM, Kalish JM, Keppler-Noreuil KM, Kosaki K, Kozel BA, Mirzaa GM, Mulvihill JJ, Nowaczyk MJM, Pagon RA, Retterer K, Rope AF, Sanchez-Lara PA, Seaver LH, Shieh JT, Slavotinek AM, Sobering AK, Stevens CA, Stevenson DA, Tan TY, Tan WH, Tsai AC, Weaver DD, Williams MS, Zackai E, Zarate YA. A dyadic approach to the delineation of diagnostic entities in clinical genomics. Am J Hum Genet. 2021 Jan 7;108(1):8-15. doi: 10.1016/j.ajhg.2020.11.013. PMID: 33417889; PMCID: PMC7820621. Abstract The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as "GENE-related phenotype descriptor" (e.g., "CFTR-related cystic fibrosis"). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships. (01/2021) (link)
  • Michelson DJ, Clark RD. Optimizing Genetic Diagnosis of Neurodevelopmental Disorders in the Clinical Setting. Clin Lab Med. 2020 Sep;40(3):231-256. doi: 10.1016/j.cll.2020.05.001. Epub 2020 Jul 3. PMID: 32718497 Abstract Progress in medical genetics has changed the practice of medicine in general and child neurology in particular. A genetic diagnosis has become critically important in determining optimal management of many neurodevelopmental disorders, making genetic testing a routine consideration of patient care in outpatient and inpatient settings. Today's child neurologists should be familiar with various genetic testing modalities and their appropriate use. Molecular genetic testing of children with unexplained developmental delays and/or congenital anomalies has a 20% to 30% chance of identifying a causative etiology. Newer methods have made genetic testing more widely available and sensitive but also more likely to produce ambiguous results. (07/2020) (link)
  • Brahmbhatt Sutariya M, Clark RD, Wilson S, Vargas L, Wang J, Herrmann P. Unbalanced Whole-Arm Translocation der(18;21)(q10;q10) in Hematological Malignancies. J Assoc Genet Technol. 2020;46(3):141-145. PMID: 32889803 Abstract Whole-arm translocations are relatively rare among hematological malignancies. There are a few reports on der(18;21)(q10;q10). This is a recurrent but rare abnormality. Only about 11 cases harboring der(18;21)(q10;q10) have been reported. However, combined der(18;21) (q10;q10) and gain of chromosome 21 is even rarer, with only three cases reported. The previous cases were with AML, AML-M2, and aCML diagnosis. We report the first case of Ph-like, B-lymphoblastic leukemia (B-ALL) with +21 and der(18;21)(q10;q10) which resulted in loss of 18p and a gain of 21q. We address tumorigenesis and morphological characteristics of hematological malignancies involving der(18;21)(q10;q10), along with a review of the literature. (03/2020)
  • Yamamoto S, Jaiswal M, Charng W-L, Gambin T, Karaca E, Mirzaa G, Wiszniewski W, Sandoval H, Haelterman NA, Xiong B, Zhang K, Bayat V, David G, Li T, Chen K, Gala U, Harel T, Pehlivan D, Penney S, Vissers LELM, de Ligt J, Jhangiani SN, Xie Y, Tsang SH, Parman Y, Sivaci M, Battaloglu E, Muzny D, Wan YW, Liu Z, Lin-Moore AT, Clark RD, Curry CJ, Link N, Schulze KL, Boerwinkle E, Dobyns WB, Allikmets R, Gibbs RA, Chen R, Lupski JR, Wangler MF, Bellen HJ. A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell. 2014 Sept 25;159(1):200-214. (09/2014)
  • Risheg H, Graham JM, Clark RD, Rogers RC, Opitz JM, Moeschler JB, Peiffer AP, May M, Joseph SM, Jones JR, Stevenson RE, Schwartz CE, Friez MJ. "A Recurrent Mutation in MED 12 leading to R961W causes Opitz-Kaveggia Syndrome." Nature Genetics 39.4 (2007): 451-453. (06/2007)
  • Dressman D, Ahearn ME, Yariz KO, Basterrecha H, Martínez F, Palau F, Barmada MM, Clark RD, Meindl A, Wirth B, Hoffman EP, Baumbach-Reardon L. X-linked infantile spinal muscular atrophy: clinical definition and molecular mapping. Genet Med. 2007 Jan;9(1):52-60. doi: 10.1097/gim.0b013e31802d8353. PMID: 17224690. Abstract Purpose: X-linked infantile spinal-muscular atrophy (XL-SMA) is a rare disorder, which presents with the clinical characteristics of hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have previously reported a single family with XL-SMA that mapped to Xp11.3-q11.2. Here we report further clinical description of XL-SMA plus an additional seven unrelated (XL-SMA) families from North America and Europe that show linkage data consistent with the same region. Methods: We first investigated linkage to the candidate disease gene region using microsatellite repeat markers. We further saturated the candidate disease gene region using polymorphic microsatellite repeat markers and single nucleotide polymorphisms in an effort to narrow the critical region. Two-point and multipoint linkage analysis was performed using the Allegro software package. Results: Linkage analysis of all XL-SMA families displayed linkage consistent with the original XL-SMA region. Conclusion: The addition of new families and new markers has narrowed the disease gene interval for a XL-SMA locus between SNP FLJ22843 near marker DXS 8080 and SNP ARHGEF9 which is near DXS7132 (Xp11.3-Xq11.1). (01/2007) (link)

Books and Chapters

  • Michelson D, Clark RD. Optimizing Genetic Diagnosis of Neurodevelopmental Disorders in the Clinical Setting in: Clinics in Laboratory Medicine, Elsevier publisher, in press (2020) (05/2020)
  • Michelson D, Clark RD. Chapter 160: Counseling Children with Neurological Disorders and their Families in Swaiman’s Pediatric Neurology: Principles and Practice. Swaiman KF, Ashwal S, Ferriero DM, Schor NF, Finkel RS, Gropman AL, Pearl PL, Shevell MI, editors. 6th ed. Elsevier publishers, 2017. (05/2017 - 05/2020)
  • Clark Robin D, Mansfield Nancy C. Retinoblastoma:Genetic Testing and Counseling. Clinical Ophthalmic Oncology: Elsevier, . 441 - 446 (10/2008 - Present)