American Journal of Medical Genetics Part A

Cover image for Vol. 173 Issue 10

Edited By: Maximilian Muenke

Impact Factor: 2.259

ISI Journal Citation Reports © Ranking: 2016: 96/166 (Genetics & Heredity)

Online ISSN: 1552-4833

Associated Title(s): American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, American Journal of Medical Genetics Part C: Seminars in Medical Genetics

Virtual Issue: The Best of Case Reports

“A case report is the publication in the medical scientific literature of a single clinical observation whose principle purpose is to generate hypotheses regarding human disease or provide insight into clinical practice.” [Carey, 2010]

Despite the fact that case reports are cited significantly less often than reviews or original articles (and thus lower the ISI impact factor for a journal), this class of scientific paper remains a time-honored and rich tradition in medical and scientific publications. Case reports occupy a crucial place in the discovery and investigation of rare diseases, an important theme in genetic medicine. Many genetic conditions were originally described as an observation of a single patient (e.g., neurofibromatosis type 1, trisomy 18, and Wolf-Hirschhorn syndrome).

The purpose of this Virtual Issue in the American Journal of Medical Genetics is to highlight and celebrate the Best of Case Reports published in the Journal in the last 6 years (and early 2013). These 54 papers, whose links are provided below, represent the top 5th centile of clinical reports published by the Journal in this time period. The choice of these papers is solely that of the Editor in Chief, but I consider them to be at the top of the taxonomy for case reports proposed in previous publications [Carey, 2006; Carey, 2010].

The ensuing papers are classified into four categorical groups: 1. Etiology, including newly recognized syndromes, confirmatory cases of new human teratogens, and observations that help identify a candidate causal gene (or region) for a phenotype; 2. Pathogenesis, including papers that demonstrate insight into a novel mechanism for human disorders; 3. Papers that help delineate the phenotype of a known condition or substantially add to its natural history; and 4. Case series of previously described syndromes.

Notably, some of these clinical reports and series were authored by a junior researcher who won the John M. Opitz Young Investigator Award for that particular year (e.g., see the papers of Doctors Sousa, Cabanillas, Unger, Shaw, and Mirzaa). Ideally, these reports represent the highest standard of papers reporting on clinical observations in the medical genetics literature.

John C. Carey
Editor-in-Chief, American Journal of Medical Genetics Part A


Carey, J.C., 2006. The Significance of Case Reports in the Advancement of Medical Scientific Knowledge. American Journal of Medical Genetics, Part A. 140A: 2131 2134.

Carey, J.C., 2010: The Importance of Case Reports in Advancing Scientific Knowledge of Rare Diseases. Advances in Experimental Medicine and Biology 686, Rare Diseases Epidemiology, page 77 to 89.


Significance of Case Reports in the Advancement of Medical Scientific Knowledge
John C. Carey. 2006. 140A:2131-2134.

Etiology/Definition/Newly Described Syndromes

A new case of 8q22.1 microdeletion restricts the critical region for Nablus mask-like facial syndrome
Anne Debost-Legrand, Eleonore Eymard-Pierre, Céline Pebrel-Richard, Laetitia Gouas, Carole Goumy, Michel Giollant, Wiem Ayed, Andreï Tchirkov, Christine Francannet and Philippe Vago. 2013. 161A:162-165.

1.9 Mb microdeletion of 21q22.11 within Braddock–Carey contiguous gene deletion syndrome region: Dissecting the phenotype
Kosuke Izumi, Susan S. Brooks, Holly A. Feret and Elaine H. Zackai. 2012. 158A:1535-1541.

A microdeletion proximal of the critical deletion region is associated with mild Wolf–Hirschhorn syndrome
Femke Hannes, Peter Hammond, Oliver Quarrell, Jean-Pierre Fryns, Koenraad Devriendt and Joris R. Vermeesch. 2012. 158A:996-1004.

Congenital heart defects in a novel recurrent 22q11.2 deletion harboring the genes CRKL and MAPK1
Jeroen Breckpot, Bernard Thienpont, Marijke Bauters, Leon-Charles Tranchevent, Marc Gewillig, Karel Allegaert, Joris R. Vermeesch, Yves Moreau and Prof. Koenraad Devriendt. 2012. 158A:574-580.

Branchial Arch Defects and 19p13.12 Microdeletion: Defining the Critical Region Into a 0.8 M Base Interval
Kenjiro Kosaki, Hideyuki Saito, Rika Kosaki, Chiharu Torii, Kazuo Kishi and Takao Takahashi. 2011. 155A:2212-2214.

Nestor-Guillermo Progeria Syndrome: A Novel Premature Aging Condition With Early Onset and Chronic Development Caused by BANF1 Mutations
Rubén Cabanillas, Juan Cadiñanos, José A.F. Villameytide, Mercedes Pérez, Jesús Longo, José M. Richard, Rebeca Álvarez, Noelia S. Durán, Rafael Illán, Daniel J. González and Carlos López-Otín. 2011. 155A:2617-2625.

Delineation of Dermatan 4-0-Sulfotransferase 1 Deficient Ehlers-Danlos Syndrome: Observation of Two Additional Patients and Comprehensive Review of 20 Reported Patients
Kenji Shimizu, Nobuhiko Okamoto, Noriko Miyake, Katsuaki Taira, Yumiko Sato, Keiko Matsuda, Noriko Akimaru, Hirofumi Ohashi, Keiko Wakui, Yoshimitsu Fukushima, Naomichi Matsumoto and Tomoki Kosho. 2011. 155A:1949-1958.

Progeroid facial features and lipodystrophy associated with a novel splice site mutation in the final intron of the FBN1 gene
Denise Horn and Peter N. Robinson. 2011. 155A:721-724.

Grade 1 Microtia, Wide Anterior Fontanel and Novel Type Tracheo-Esophageal Fistula in Methimazole Embryopathy
Karen W. Gripp, Ranita Kuryan, Rhonda E. Schnur, Murtuza Kothawala, Lauren R. Davey, Michael J. Antunes, Kirk W. Reichard, Adele Schneider and Bryan D. Hall. 2011. 155A:526-533.

A New Syndrome with Multiple Capillary Malformations, Intractable Seizures, and Brain and Limb Anomalies
Melissa T. Carter, Michael T. Geraghty, Laura De La Cruz, R. Ross Reichard, Luigi Boccuto, Charles E. Schwartz and Carol L. Clericuzio. 2011. 155A:301-306.

Marfan syndrome with neonatal progeroid syndrome-like lipodystrophy associated with a novel frameshift mutation at the 3′ terminus of the FBN1-gene
Luitgard M. Graul-Neumann, Tina Kienitz, Peter N. Robinson, Sevjidmaa Baasanjav, Benjamin Karow, Gabriele Gillessen-Kaesbach, Raimund Fahsold, Hartmut Schmidt, Katrin Hoffmann and Eberhard Passarge. 2010. 152A:2749-2755.

New Lethal Skeletal Dysplasia with Dandy-Walker Malformation, Congenital Heart Defects, Abnormal Thumbs, Hypoplastic Genitalia, and distinctive Facies
Cathy A. Stevens and Ralph S. Lachman. 2010. 152A:1915-1918.

Syndromic Mental Retardation with Thrombocytopenia Due to 21q22.11q22.12 Deletion: Report of Three Patients
Eleni Katzaki, Gilles Morin, Marzia Pollazzon, Filomena Tiziana Papa, Sabrina Buoni, Joussef Hayek, Joris Andrieux, Laure Lecerf, Cornel Popovici, Aline Receveur, Michèle Mathieu-Dramard, Alessandra Renieri, Francesca Mari and Nicole Philip. 2010. 152A:1711-1717.

Metopic Craniosynostosis Due to Mutations in GLI3: A Novel Association
Donna M. McDonald-McGinn, Holly Feret, Hyun-Duck Nah, Scott P. Bartlett, Linton A. Whitaker and Elaine H. Zackai. 2010. 152A:1654-1660.

A New Ehlers-Danlos Syndrome with Craniofacial Characteristics, Multiple Congenital Contractures, Progressive Joint and Skin Laxity, and Multisystem Fragility-Related Manifestations
Tomoki Kosho, Noriko Miyake, Atsushi Hatamochi, Jun Takahashi, Hiroyuki Kato, Teruyoshi Miyahara, Yasuhiko Igawa, Hiroshi Yasui, Tadao Ishida, Kurahito Ono, Takashi Kosuda, Akihiko Inoue, Mohei Kohyama, Tadashi Hattori, Hirofumi Ohashi, Gen Nishimura, Rie Kawamura, Keiko Wakui, Yoshimitsu Fukushima and Naomichi Matsumoto. 2010. 152A:1333-1346.

Postnatal Growth Retardation, Facial Dysmorphism, Spondylocarpal Sysnostosis, Cardiac Defect, and Inner Ear Malformation (Cardiospondylocarpofacial Syndrome?) - A Distinct Syndrome?
Sérgio B. Sousa, Geneviéve Baujat, Véronique Abadie, Damien Bonnet, Daniel Sidi, Arnold Munnich, Deborah Krakow and Valérie Cormier-Daire. 2010. 152A:539-546.

Characterization of a New X-Linked Mental Retardation Syndrome with Microcephaly, Cortical Malformation, and Thin Habitus
Christèle du Souich, Athena Chou, Jingyi Yin, Tracey Oh, Tanya N. Nelson, Jane Hurlburt, Laura Arbour, Robin Friedlander, Barbara C. McGillivray, Nataliya Tyshchenko, Andreas Rump, Kenneth J. Poskitt, Michelle K. Demos, Margot I. Van Allen and Cornelius F. Boerkoel. 2009. 149A:2469-2478.

Case Report Supporting That the Barber-Say and Ablepharon Macrostomia Syndromes Could Represent One Disorder
Jennifer Haensel, Nicolai Kohlschmidt, Susanne Pitz, Annerose Keilmann, Martin Zenker, Reinhard Ullmann, Thomas Haaf and Oliver Bartsch. 2009. 149A:2236-2240.

Reviewing the evidence for mycophenolate mofetil as a new teratogen: Case report and review of the literature
Marlene T. Anderka, Angela E. Lin, Dianne N. Abuelo, Allen A. Mitchell and Sonja A. Rasmussen. 2009. 149A:1241-1248.

A Novel Chromosome 19p13.12 Deletion in a Child With Multiple Congenital Anomalies
Daniel R. Jensen, Donna M. Martin, Stephen Gebarski, Trilochan Sahoo, Ellen K. Brundage, A. Craig Chinault, Edgar A. Otto, Moumita Chaki, Friedhelm Hildebrandt, Sau Wai Cheung and Marci M. Lesperance. 2009. 149A:396-402.

Co-occurrence of 4p16.3 Deletions with Both Paternal and Maternal Duplications of 11p15: Modification of the Wolf-Hirschhorn Syndrome Phenotype by Genetic Alterations Predicted to Result in Either a Beckwith-Wiedemann or Russell-Silver Phenotype
Sarah T. South, Heidi Whitby, Teresa Maxwell, Emily Aston, Arthur R. Brothman and John C. Carey. 2008. 146A:2691-2697.

Progressive and Symmetric Supraorbital Hyperostosis with Bony and Soft Tissue Overgrowth in an Ethiopian Female: A Newly Recognized Overgrowth Syndrome?
Margaret P. Adam, Joyce A. Kobori, Kristina Cusmano-Ozog, Kelly M. Chen and H. Eugene Hoyme. 2008. 146A:543-547.

In Utero Exposure to Mycophenolate Mofetil: A Characteristic Phenotype?
Antonio Perez-Aytes, Ana Ledo, Virginia Boso, Pilar Sáenz, Eva Roma, José Luis Poveda and Maximo Vento. 2008. 146A:1-7.

Newly Delineated Syndrome of Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi (CLOVE Syndrome) in Seven Patients
Julie C. Sapp, Joyce T. Turner, Jiddeke M. van de Kamp, Fleur S. van Dijk, R. Brian Lowry and Leslie G. Biesecker. 2007. 143A:2944-2958.

Two Unique Patients with Novel Microdeletions in 4p16.3 That Exclude the WHS Critical Regions: Implications for Critical Region Designation
Sarah T. South, Steven B. Bleyl and John C. Carey. 2007. 143A:2137-2142.

Craniofacial Anomalies, Humero-Radial Synostosis, Rhizomelic Limb Shortness: Previously Unrecognized Autosomal Recessive Syndrome
Zuhair N. Al-Hassnan and Ahmad S. Teebi. 2007. 143A:521-527.


Somatic Mosaicism Contributes to Phenotypic Variation in Timothy Syndrome
Susan P. Etheridge, Neil E. Bowles, Cammon B. Arrington, Thomas Pilcher, Alan Rope, Arthur A.M. Wilde, Marielle Alders, Elizabeth V. Saarel, Rene Tavernier, Katherine W. Timothy and Martin Tristani-Firouzi. 2011. 155A:2578-2583.

Familial Acampomelic Form of Campomelic Dysplasia Caused by a 960 kb Deletion Upstream of SOX9
Claire Lecointre, Olivier Pichon, Antoine Hamel, Yves Heloury, Laurence Michel-Calemard, Yves Morel, Albert David and Cédric Le Caignec. 2009. 149A:1183-1189.

Male-to-Male Transmission of Costello Syndrome: G12S HRAS Germline Mutation Inherited from a Father with Somatic Mosaicism
Katia Sol-Church, Deborah L. Stabley, Laurie A. Demmer, Abigail Agbulos, Angela E. Lin, Leslie Smoot, Linda Nicholson and Karen W. Gripp. 2009. 149A:315-321.

Costello Syndrome Associated With Novel Germline HRAS Mutations: An Attenuated Phenotype?
Karen W. Gripp, A. Micheil Innes, Marni E. Axelrad, Tanya L. Gillan, Jillian S. Parboosingh, Christine Davies, Norma J. Leonard, Monique Lapointe, Daniel Doyle, Sarah Catalano, Linda Nicholson, Deborah L. Stabley and Katia Sol-Church. 2008. 146A:683-690.

Mandibulofacial Dysostosis in a Patient With a De Novo 2;17 Translocation That Disrupts the HOXD Gene Cluster
David A. Stevenson, Steven B. Bleyl, Teresa Maxwell, Arthur R. Brothman and Sarah T. South. 2007. 143A:1053-1059.

Natural History/Delineation

Co-Occurrence of Severe Goltz-Gorlin Syndrome and Pentalogy of Cantrell - Case Report and Review of the Literature
Robert Smigiel, Aleksandra Jakubiak, Maria Paola Lombardi, Wojciech Jaworski, Ryszard Slezak, Dariusz Patkowski and Raoul C. Hennekam. 2011. 155A:1102-1105.

The Atypical 16p11.2 Deletion: A Not So Atypical Microdeletion Syndrome?
Daniela Q.C.M. Barge-Schaapveld, Saskia M. Maas, Abeltje Polstra, Lia C. Knegt and Raoul C.M. Hennekam. 2011. 155A:1066-1072.

Petty Syndrome and Fontaine-Farriaux Syndrome: Delineation of a Single Syndrome
Stephen R. Braddock, Holly H. Ardinger, Chun-Song Yang, Bryce M. Paschal and Bryan D. Hall. 2010. 152A:1718-1723.

A Second Patient with Tsukahara Syndrome: Type A1 Brachydactyly, Short Stature, Hearing Loss, Microcephaly, Mental Retardation, and Ptosis
Gülen Eda Utine, Jeroen Breckpot, Bernard Thienpont, Yasemin Alanay, Cemalettin Aksoy, Koray Boduroğlu and Koenraad Devriendt. 2010. 152A:947-949.

Goldenhar Phenotype in a Child With Distal 22q11.2 Deletion and Intracranial Atypical Teratoid Rhabdoid Tumor
Lucie Lafay-Cousin, Eric Payne, Douglas Strother, Judy Chernos, Michael Chan and Francois P. Bernier. 2009. 149A:2855-2859.

Fontaine-Farriaux Syndrome: A Recognizable Craniosynostosis Syndrome with Nail, Skeletal, Abdominal, and Central Nervous System Anomalies
Marco Castori, Evelina Silvestri, Lucia Pedace, Giuseppina Marseglia, Alessia Tempera, Ivana Antigoni, Francesca Torricelli, Silvia Majore and Paola Grammatico. 2009. 149A:2193-2199.

A Complex TFAP2A Allele Is Associated With Branchio-Oculo-Facial Syndrome and Inner Ear Malformation in a Deaf Child
Mustafa Tekin, Aslı Sırmacı, Berrin Yüksel-Konuk, Suat Fitoz and Levent Sennaroğlu. 2009. 149A:427-430.

Filippi Syndrome: Further Clinical Characterization
Agatino Battaglia, Tiziana Filippi, Silvia Pusceddu and Charles A. Williams. 2008. 146A:1848-1852.

Expanding Spectrum of Congenital Disorder of Glycosylation Ig (CDG-Ig): Sibs with a Unique Skeletal Dysplasia, Hypogammaglobulinemia, Cardiomyopathy, Genital Malformations, and Early Lethality
Christian Kranz, Alice A. Basinger, Müge Güçsavaş-Çalıkoğlu, Liangwu Sun, Cynthia M. Powell, Frederick W. Henderson, Arthur S. Aylsworth and Hudson H. Freeze. 2007. 143A:1371-1378.

Increasing Knowledge of PTEN Germline Mutations: Two Additional Patients With Autism and Macrocephaly
Gail E. Herman, Eric Butter, Benedicta Enrile, Matthew Pastore, Thomas W. Prior and Annemarie Sommer. 2007. 143A:589-593.

Tricho-Hepato-Enteric Syndrome: A Case of Hemochromatosis with Intractable Diarrhea, Dysmorphic Features, and Hair Abnormality
Imad Dweikat, Mutaz Sultan, Nizar Maraqa, Tareq Hindi, Sara Abu-Rmeileh and Bassam Abu-Libdeh. 2007. 143A:581-583.


Maternal vitamin K deficient embryopathy: Association with hyperemesis gravidarum and Crohn disease
Helga V. Toriello, Miriam Erick, Jean-Luc Alessandri, Diana Bailey, Nicola Brunetti-Pierri, Helen Cox, Alan Fryer, Denise Marty, Charles McCurdy, John B. Mulliken, Helen Murphy, Joseph Omlor, Richard M. Pauli, Judith D. Ranells, Amarillis Sanchez-Valle, Ana Tobiasz, Lionel Van Maldergem and Angela E. Lin. 2013. 161A:417-429.

Phenotypic variability in hyperphosphatasia with seizures and neurologic deficit (Mabry syndrome)
Miles D. Thompson, Tony Roscioli, Carlo Marcelis, Marjan M. Nezarati, Irene Stolte-Dijkstra, Frances J. Sharom, Peihua Lu, John A. Phillips, Elizabeth Sweeney, Peter N. Robinson, Peter Krawitz, Helger G. Yntema, Danielle M. Andrade, Han G. Brunner and David E.C. Cole. 2012. 158A:553-558.

Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: Two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis
Ghayda M. Mirzaa, Robert L. Conway, Karen W. Gripp, Tally Lerman-Sagie, Dawn H. Siegel, Linda S. deVries, Dorit Lev, Nancy Kramer, Elizabeth Hopkins, John M. Graham Jr and William B. Dobyns. 2012. 158A:269-291.

Pierpont syndrome: A collaborative study
Emma M.M. Burkitt Wright, Mohnish Suri, Susan M. White, Nicole de Leeuw, Anneke T. Vulto-van Silfhout, Fiona Stewart, Shane McKee, Sahar Mansour, Fiona C Connell, Maya Chopra, Edwin P. Kirk, Koen Devriendt, Willie Reardon, Han Brunner and Dian Donnai. 2011. 155A:2203-2211.

Phenotype and natural history in Marshall–Smith syndrome
Adam C. Shaw, Inge D.C. van Balkom, Mislen Bauer, Trevor R.P. Cole, Marie-Ange Delrue, Arie Van Haeringen, Eva Holmberg, Samantha J.L. Knight, Geert Mortier, Sheela Nampoothiri, Silvija Pušeljić, Martin Zenker, Valerie Cormier-Daire and Raoul C.M. Hennekam. 2010. 152A:2714-2726.

The phenotype of Floating–Harbor syndrome in 10 patients
Susan M. White, Angela Morgan, Annette Da Costa, Didier Lacombe, Samantha J.L. Knight, Richard Houlston, Margo L. Whiteford, Ruth A. Newbury-Ecob and Jane A. Hurst. 2010. 152A:821-829.

Pulmonary Hypoloplasia-Diaphragmatic Hernia-Anophthalmia-Cardiac Defect (PDAC) Syndrome Due to STRA6 Mutations - What are the Minimal Criteria?
Reeval Segel, Ephrat Levy-Lahad, Francesca Pasutto, Elie Picard, Anita Rauch, Gheona Alterescu and Michael S. Schimmel. 2009. 149A:2457-2463.

Nicolaides-Baraitser Syndrome: Delineation of the Phenotype
Sérgio B. Sousa, Omar A. Abdul-Rahman, Armand Bottani, Valérie Cormier-Daire, Alan Fryer, Gabriele Gillessen-Kaesbach, Denise Horn, Dragana Josifova, Alma Kuechler, Melissa Lees, Kay MacDermot, Alex Magee, Fanny Morice-Picard, Elizabeth Rosser, Ajoy Sarkar, Nora Shannon, Irene Stolte-Dijkstra, Alain Verloes, Emma Wakeling, Louise Wilson and Raoul C.M. Hennekam. 2009. 149A:1628-1640.

15q overgrowth syndrome: A newly recognized phenotype associated with overgrowth, learning difficulties, characteristic facial appearance, renal anomalies and increased dosage of distal chromosome 15q
Katrina Tatton-Brown, Daniela T. Pilz, Karen Helene Örstavik, Michael Patton, John C.K. Barber, Morag N. Collinson, Vivienne K. Maloney, Shuwen Huang, John A. Crolla, Karen Marks, Eli Ormerod, Peter Thompson, Zafar Nawaz, Christa Lese-Martin, Susan Tomkins, Paula Waits, Nazneen Rahman and Meriel McEntagart. 2009. 149A:147-154.

Chondrodysplasia Punctata Associated With Maternal Autoimmune Diseases: Expanding the Spectrum from Systemic Lupus Erythematosus (SLE) to Mixed Connective Tissue Disease (MCTD) and Scleroderma Report of Eight Cases
David Chitayat, Sarah Keating, Dina J. Zand, Teresa Costa, Elaine H. Zackai, Earl Silverman, George Tiller, Sheila Unger, Stephen Miller, John Kingdom, Ants Toi and Cynthia J.R. Curry. 2008. 146A:3038-3053.

Clinical and Radiographic Delineation of Odontochondrodysplasia
Sheila Unger, Franco Antoniazzi, Milena Brugnara, Yasemin Alanay, Ahmet Caglayan, Katherine Lachlan, Shiro Ikegawa, Gen Nishimura, Bernhard Zabel, Jürgen Spranger and Andrea Superti-Furga. 2008. 146A:770-778.

Manitoba oculotrichoanal (MOTA) syndrome: Report of eight new cases
Chumei Li, Sandra L Marles, Cheryl R. Greenberg, Bernard N. Chodirker, Jiddeke van de Kamp, Anne Slavotinek and Albert E. Chudley. 2007. 143A:853-857.