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Endocr Rev 2018 Jun 18. Epub 2018 Jun 18.

INSERM UMR 1048, Institute of Cardiovascular and Metabolic Diseases (I2MC), University of Toulouse Paul Sabatier, Toulouse, France.

Noonan syndrome (NS; Mendelian Inheritance in Men (MIM) ♯163950) and related syndromes (Noonan syndrome with multiple lentigines (NS-ML, formerly called LEOPARD syndrome; MIM ♯151100), Noonan-like syndrome with loose anagen hair (NS-LAH; MIM ♯607721), Costello syndrome (CS; MIM ♯218040), Cardio-Facio-Cutaneous syndrome (CFCS; MIM ♯115150), type I Neurofibromatosis (NF1; MIM ♯162200), and Legius syndrome (LS; MIM ♯611431)) are a group of related genetic disorders, associating distinctive facial features, cardiopathies, growth and skeletal abnormalities, developmental delay/mental retardation, and tumor predisposition. Clinically described more than 50 years ago, disease genes have been identified throughout the three last decades, providing a molecular basis to better understand their physiopathology and to identify targets for therapeutic strategies. Most of those genes encode proteins belonging to or regulating the so-called RAS/Mitogen-Activated Protein Kinase (MAPK) signaling pathway, so that these syndromes have been gathered under the naming Rasopathies. Read More

Am J Med Genet A 2018 May 7. Epub 2018 May 7.

Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.

Systemic lupus erythematosus (SLE) has been reported among patients with RASopathy. Five patients have been reported: three with SHOC2 variants, one with a PTPN11 variant, and one with a KRAS variant. SHOC2 variant might represent a relatively common predisposing factor for SLE among the RASopathy genes. Read More

J Pediatr 2018 Apr 25. Epub 2018 Apr 25.

Henry Ford Hospital Department of Dermatology Detroit, Michigan.

Pediatr Dermatol 2018 May 26;35(3):388-391. Epub 2018 Mar 26.

Department of Dermatology and Cutaneous Surgery, Jackson Health System/Miller School of Medicine, University of Miami, Miami, FL, USA.

Background/objectives: Short anagen syndrome is a hair cycle disorder usually diagnosed in early childhood and characterized by short hair length due to short duration of the anagen phase. The objective was to review the presentation and demographic characteristics of short anagen syndrome and compare them with the most common differential diagnosis, loose anagen syndrome.

Methods: A retrospective review of eight children with short anagen syndrome was performed at the University of Miami Outpatient Dermatology Clinic. Read More

Australas J Dermatol 2018 Mar 22. Epub 2018 Mar 22.

Sinclair Dermatology, Melbourne, Victoria, Australia.

Clin Case Rep 2017 Jul 1;5(7):1152-1154. Epub 2017 Jun 1.

Department of DermatologyUniversity of Massachusetts Medical School281 Lincoln StreetWorcester01605Massachusetts.

We report a case of Noonan syndrome with loose anagen hair (NS/LAH), a rare variant of Noonan syndrome, with associated trichorrhexis nodosa and trichoptilosis. The mutation may be responsible for these additional hair shaft defects, revealing the importance of microscopic examination of hairs in these patients. Read More

Am J Med Genet A 2017 May 3;173(5):1309-1318. Epub 2017 Apr 3.

Center for Applied Clinical Genomics, A. I. duPont Hospital for Children/Nemours, Wilmington, Delaware.

Costello syndrome is part of the RASopathies, a group of neurocardiofaciocutaneous syndromes caused by deregulation of the RAS mitogen-activated protein kinase pathway. Heterozygous mutations in HRAS are responsible for Costello syndrome, with more than 80% of the patients harboring the specific p.Gly12Ser variant. Read More

Am J Med Genet A 2017 Mar;173(3):824-828

Unidade de Genética Clínica, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

We report on a 12-year-old Brazilian boy with the p.Pro49Arg mutation in PPP1CB, a novel gene associated with RASopathies. This is the fifth individual described, and the fourth presenting the same variant, suggesting a mutational hotspot. Read More

Arch Med Sci 2017 Feb 19;13(1):215-222. Epub 2016 Dec 19.

Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Read More

J Am Acad Dermatol 2017 Mar 20;76(3):472-477. Epub 2016 Dec 20.

Division of Dermatology, Ottawa Hospital, Ottawa, Ontario, Canada. Electronic address:

Background: The hair pull test lacks validation and has unclear pretest guidelines.

Objective: We sought to quantify normal hair pull test values and elucidate the effect of pretest hair washing and brushing. The impact of hair texture and lifestyle was also examined. Read More

Am J Med Genet A 2017 02 21;173(2):565-567. Epub 2016 Nov 21.

Division of Genetics, Department of Pediatrics, Louisiana State University Health Sciences Center School of Medicine, and Children's Hospital, New Orleans, Louisiana.

Acta Dermatovenerol Croat 2016 Jun;24(2):150-3

Jana Zímová, MD. Department of Dermatology. University Hospital Ostrava. 17. listopadu 1790. 708 52 Ostrava - Poruba. Czech Republic;

Trichotillomania (TTM) is defined by the Diagnostics and Statistic Manual of Mental Disorders, 4th edition (DMS-IV) as hair loss from a patient`s repetitive self-pulling of hair. The disorder is included under anxiety disorders because it shares some obsessive-compulsive features. Patients have the tendency towards feelings of unattractiveness, body dissatisfaction, and low self-esteem (1,2). Read More

Hum Mol Genet 2016 09 27;25(17):3824-3835. Epub 2016 Jul 27.

Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy

SHOC2 is a scaffold protein composed almost entirely by leucine-rich repeats (LRRs) and having an N-terminal region enriched in alternating lysine and glutamate/aspartate residues (KEKE motifs). SHOC2 acts as a positive modulator of the RAS-RAF-MEK-ERK signalling cascade by favouring stable RAF1 interaction with RAS. We previously reported that the p. Read More

Pediatr Dermatol 2016 Sep 19;33(5):507-10. Epub 2016 Jul 19.

Division of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Background/objectives: Loose anagen syndrome (LAS) is a disorder of abnormal anchorage of the hair to the scalp. Its symptoms include an inability to grow hair long and hair that is easily pulled out.

Methods: We conducted a retrospective chart review of patients with LAS over the last 10 years at the Children's Hospital of Philadelphia and found 37 cases. Read More

Am J Med Genet A 2016 Sep 5;170(9):2237-47. Epub 2016 Jun 5.

Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.

Noonan syndrome is a rasopathy caused by mutations in multiple genes encoding components of the RAS/MAPK pathway. Despite its variable phenotype, limited genotype-phenotype correlations exist. Noonan syndrome with loose anagen hair (NS-LAH) is characterized by its distinctive hair anomalies, developmental differences, and structural brain abnormalities and is caused by a single recurrent missense SHOC2 mutation. Read More

Indian Dermatol Online J 2016 Jan-Feb;7(1):56-7

Department of Dermatology, People's College of Medical Sciences and Research Centre, Bhopal, Madhya Pradesh, India.

Int J Trichology 2015 Jul-Sep;7(3):138-9

Department of Pediatric Dermatology, Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India.

Prog Pediatr Cardiol 2015 Jul;39(1):13-19

Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Rome, Italy.

Noonan syndrome and related disorders (Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. Read More

Curr Probl Dermatol 2015 20;47:55-66. Epub 2015 Feb 20.

Hair diseases represent frequent complaints in dermatology clinics, and they can be caused by a number of conditions reflected by specific diagnoses. Hair loss is not uncommon in the pediatric group, but its patterns in this group are different from those seen in adults. Additionally, in children, these disorders can have psychological effects that can interfere with growth and development. Read More

Arch Dermatol Res 2015 Nov 28;307(9):841-7. Epub 2015 Jul 28.

Institute of Inflammation and Repair, University of Manchester, Manchester, UK.

Spermidine (Spd), the prototypic polyamine, has been shown to be essential for hair follicle (HF) growth. However, Spd can be readily converted into other polyamines, and is physiologically unstable. Therefore, to assess its individual functions on HFs, we used the metabolically stable Spd analog N(1)-methylspermidine (N(1)-MeSpd). Read More

Am J Med Genet A 2015 Oct 19;167A(10):2425-9. Epub 2015 Jun 19.

Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is caused by a heterozygous c.4A>G mutation in SHOC2. Most cases exhibit both growth hormone deficiency (GHD) and growth hormone insensitivity (GHI) and thus require a high dose of growth hormone (GH) therapy (e. Read More

J Dermatol Case Rep 2015 Mar 31;9(1):1-5. Epub 2015 Mar 31.

Department of Dermatology, Medical University of Warsaw, Poland;

Background: Loose anagen hair syndrome (LAHS) is typically diagnosed in girls older than 2 years who present with hair that "will not grow". Hair microscopic examination shows absent inner and outer root sheaths, ruffling of the cuticle on the proximal hair shaft and deformed pigmented anagen bulbs.

Objective: The aim of the study was to assess whether there are characteristic trichoscopic features favoring the diagnosis of LAHS. Read More

BMC Neurol 2015 Apr 16;15:55. Epub 2015 Apr 16.

Department of Clinical Neurosciences, Lausanne University Hospital (CHUV), Rue du Bugnon 21, 1011, Lausanne, Switzerland.

Background: LEOPARD syndrome (LS) belongs to the family of neuro-cardio-facio-cutaneous syndromes, which include Neurofibromatosis-1 (NF1), Noonan syndrome, Costello Syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair and Legius syndrome. These conditions are caused by mutations in genes encoding proteins involved in the RAS-MAPK cellular pathway. Clinical heterogeneity and phenotype overlaps across those different syndromes is already recognized. Read More

Am J Med Genet A 2015 Jun 9;167(6):1285-8. Epub 2015 Apr 9.

Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.

Moyamoya disease is a unique chronic cerebrovascular condition caused by progressive stenosis of the arteries around the circle of Willis with prominent arterial collateral circulation. Noonan-like syndrome with loose anagen hair (NSLH) is characterized by short stature, characteristic facial phenotype, darkly pigmented and hairless skin, mild psychomotor delay with attention deficit disorder, and easily pluckable, sparse, thin, slow growing hair. Mutations in SHOC2 have been reported to underlie NSLH. Read More

Am J Med Genet A 2015 Aug 5;167A(8):1902-7. Epub 2015 Apr 5.

Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.

Noonan-like syndrome with loose anagen hair (NSLH), also known as Mazzanti syndrome, is a RASopathy characterized by craniofacial features resembling Noonan syndrome, cardiac defects, cognitive deficits and behavioral issues, reduced growth generally associated with GH deficit, darkly pigmented skin, and an unique combination of ectodermal anomalies. Virtually all cases of NSLH are caused by an invariant and functionally unique mutation in SHOC2 (c.4A>G, p. Read More

Rev Med Liege 2014 Dec;69(12):686-91

The diagnosis of most alopecia problems is based on the clinical history and a well conducted clinical examination. The additional contributions of dermoscopy, trichoscopy and trichogram are helpful. However, a scalp biopsy is occasionally necessary to establish the correct diagnosis. Read More

Pediatr Dermatol 2015 May-Jun;32(3):e128-9. Epub 2015 Mar 17.

Division of Pediatric Dermatology, Johns Hopkins Hospital, Baltimore, Maryland.

We present the case of 7-year-old African American girl with loose anagen syndrome. Although this is a common cause of hair loss in Caucasian children, and there have been reports of cases occurring in dark-skinned children of North African and Middle Eastern descent, to our knowledge there have been no cases reported in black children of sub-Saharan African ancestry. We present this case to broaden the differential diagnosis of hair loss in African Americans. Read More

Pediatr Neurol 2015 Mar 3;52(3):352-5. Epub 2014 Dec 3.

Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea; Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Background: Noonan-like syndrome with loose anagen hair is one of the RASopathies characterized by Noonan syndrome-like features with unique ectodermal abnormalities. This syndrome is caused by mutations in the SHOC2 gene. We encountered a patient with moyamoya syndrome associated with Noonan-like syndrome with loose anagen hair presenting with transient ischemic attacks. Read More

Indian Dermatol Online J 2014 Oct;5(4):548-9

Department of Dermatology, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai, Maharashtra, India.

Am J Med Genet A 2014 Dec 20;164A(12):3120-5. Epub 2014 Oct 20.

Department of Paediatrics, University of Torino, Torino, Italy.

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) is a developmental disorder clinically related to Noonan syndrome (NS) and characterized by facial dysmorphisms, postnatal growth retardation, cardiac anomalies (in particular dysplasia of the mitral valve and septal defects), variable neurocognitive impairment, and florid ectodermal features. A distinctive trait of NS/LAH is its association with easily pluckable, slow growing, sparse, and thin hair. This rare condition is due to the invariant c. Read More

Hum Mutat 2014 Nov 11;35(11):1290-4. Epub 2014 Sep 11.

Division of Medical Genetics and Genomic Medicine, Vanderbilt University, Nashville, Tennessee.

Rasopathies are a group of genetic disorders caused by germline mutations in multiple genes of the Extracellular signal-Regulated Kinases 1 and 2 (ERK1/2) pathway. The only previously identified missense mutation in SHOC2, a scaffold protein of the ERK1/2 pathway, led to Noonan-like syndrome with loose anagen hair. Here, we report a novel mutation in SHOC2(c. Read More

Am J Med Genet A 2014 Aug 9;164A(8):2036-42. Epub 2014 Apr 9.

Department of Pediatrics, University of Hawaii, Honolulu, Hawaii.

There is limited information available related to the perinatal course of cardiofaciocutaneous syndrome (CFC) compared to other syndromes within the Ras-MAP kinase pathway (rasopathies) such as Noonan and Costello syndrome. Retrospective chart review revealed four cases of CFC with molecular confirmation between 2005 and 2012 at Hawaii's largest obstetric and pediatric referral center. We report on details of the prenatal, neonatal, and infancy course and long-term follow-up beyond infancy in two patients. Read More

Pediatr Clin North Am 2014 Apr 21;61(2):427-42. Epub 2014 Jan 21.

Section of Dermatology, Department of Pediatrics, The Children's Hospital of Philadelphia, 3550 Market Street, 2nd Floor Dermatology, Philadelphia, PA 19104, USA. Electronic address:

Alopecia in childhood is a source of high concern, frustration, and anxiety. Delineating types of alopecia and those that are chronic or potentially related to underlying medical problems is important. There are 5 common types of hair loss in children: alopecia related to tinea capitis, alopecia areata spectrum/autoimmune alopecia, traction alopecia, telogen effluvium, and trichotillomania/trichotillosis. Read More

Pediatr Dermatol 2014 May-Jun;31(3):389-90. Epub 2014 Mar 6.

Division of Dermatology, University Medicine Cluster, National University Hospital, Singapore.

A 2-year-old girl with a diagnosis of loose anagen hair syndrome was treated with a tapering regime of minoxidil 5% solution over 28 months, resulting in quick, significant clinical improvement with no adverse effects. Read More

G Ital Dermatol Venereol 2014 Feb;149(1):1-13

Department of Internal Medicine and Medical Specialties, Unit of Dermatology Sapienza University, Rome, Italy -

Congenital abnormalities of the hair shaft are conditions in most cases linked to chemical, biochemical, and morphological alterations, genetically determined. These alterations may be associated with a larger array of symptoms, as mentioned above, or may occur isolated. The number of genes involved and their penetration are responsible for the mode of transmission, severity, and phenotypic expression of the disease. Read More

Am J Med Genet A 2014 Apr 23;164A(4):1075-8. Epub 2014 Jan 23.

Servicio de Genética del Hospital Fundación Jiménez Díaz de Madrid, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.

Am J Med Genet A 2014 May 23;164A(5):1218-21. Epub 2014 Jan 23.

Department of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM 607721) due to a missense mutation c.4A>G in SHOC2 predicting p.Ser2Gly has been described recently. Read More

Am J Med Genet A 2014 Apr 23;164A(4):1015-20. Epub 2014 Jan 23.

Neonatologic Unit, Obstetric and Paediatric Department, Istituto di Ricovero e Cura a Carattere Scientifico, S. Maria Nuova Hospital, Reggio Emilia, Italy.

Fetal hydrops is a condition resulting from interstitial fluid accumulation in fetal compartments secondary to increased capillary permeability and characterized by high rates of perinatal mortality and morbidity. Clinical features include skin edema, hydrothorax, pericardial effusion, ascites with or without polyhydramnios, and placental edema. While it may occur as associated feature in multiple disorders, it has been documented to recur in Noonan syndrome, the most common disorder among RASopathies, but also in cardiofaciocutaneous and Costello syndromes. Read More

Am J Med Genet A 2014 Apr 23;164A(4):934-42. Epub 2014 Jan 23.

Dipartimento di Neuroscienze, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.

Here, we describe neurobehavioral features in patients with RASopathies (i.e., Noonan syndrome, LEOPARD syndrome, Costello syndrome, and cardiofaciocutaneous syndrome), developmental disorders caused by mutations in genes coding transducers participating in the RAS-MAPK signaling cascade. Read More

BMC Med Genet 2014 Jan 23;15:14. Epub 2014 Jan 23.

Cytogenetics, Medical Genetics and Pediatric Cardiology, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.

Background: Noonan syndrome is an autosomal dominant developmental disorder with a high phenotypic variability, which shares clinical features with other rare conditions, including LEOPARD syndrome, cardiofaciocutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. This group of related disorders, so-called RASopathies, is caused by germline mutations in distinct genes encoding for components of the RAS-MAPK signalling pathway. Due to high number of genes associated with these disorders, standard diagnostic testing requires expensive and time consuming approaches using Sanger sequencing. Read More

J Investig Dermatol Symp Proc 2013 Dec;16(1):S63-4

Department of Dermatology, University of California, San Francisco, California, USA.

The differential diagnosis of a strongly positive and painless hair pull test includes alopecia areata and loose anagen syndrome. A hair mount examined with low power light microscopy easily clarifies the diagnosis. Read More

Pediatr Dev Pathol 2014 Jan-Feb;17(1):36-43. Epub 2013 Nov 19.

1  Department of Pathology, Children's Mercy Hospitals and Clinics, Kansas City, MO, USA.

Abnormalities in the hair can be congenital or acquired conditions. Examples of genetic disorders with associated hair abnormalities include Menkes syndrome, Netherton syndrome, uncombable hair syndrome, trichothiodystrophy, and loose anagen hair syndrome. Acquired hair abnormalities can be associated with grooming or use of various hair products. Read More

Am J Med Genet A 2013 Nov 3;161A(11):2756-61. Epub 2013 Oct 3.

Pediatric Endocrinology and Rare Diseases, Department of Pediatrics, S.Orsola-Malpighi University Hospital - University of Bologna, Bologna, Italy.

Noonan-like syndrome with loose anagen hair (NS/LAH or Mazzanti Syndrome) is caused by a single missense mutation in SHOC2 promoting tN-myristoylation of the encoded protein. Cardinal features include facial features resembling NS, short stature often associated with proven growth hormone deficiency (GHD), typical ectodermal anomalies, and distinctive behavior. Overall, the clinical features are more severe than those generally observed in NS, even though the phenotype improves with age. Read More

Indian J Dermatol Venereol Leprol 2013 Sep-Oct;79(5):604-12

Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Disturbances of hair follicle cycling lie at the heart of most hair growth disorders, and have dramatic effects on visible hair growth and shedding. The two common disorders due to aberration in hair follicle cycling are telogen and anagen effluvium. Though a lot of literature addresses the problem of telogen effluvium, there are not many reviews on anagen effluvium or anagen hair loss. Read More

Int J Trichology 2013 Jan;5(1):45-6

Department of Dermatology and Cutaneous Surgery, University of Miami, Florida, USA.

Short anagen syndrome (SAS) is a condition in which hair does not grow long. It usually perceived by parents in children around 2-4 years of age. It is a benign disease of the hair cycle. Read More

Pediatr Dermatol 2013 Sep-Oct;30(5):579-83. Epub 2013 Aug 13.

Department of Dermatology, Venereology and Leprosy, People's College of Medical Sciences & Research Centre, Bhopal, MP, India.

Loose anagen hair syndrome (LAHS) is an uncommonly reported autosomal dominant hair disorder with incomplete penetrance that primarily affects children but is occasionally seen in adults. LAHS is characterized by the ability to easily and painlessly extract unsheathed anagen hairs from the scalp with gentle traction. The hair is sparse and does not grow long. Read More

Am J Med Genet A 2013 Oct 5;161A(10):2420-30. Epub 2013 Aug 5.

Division of Medical Genetics, A. I. duPont Hospital for Children, Wilmington, Delaware.

Noonan syndrome is a heterogenous rasopathy typically presenting with short stature, characteristic facial features, cardiac abnormalities including pulmonic valve stenosis, ASD and hypertrophic cardiomyopathy (HCM), cryptorchidism, ectodermal abnormalities, and learning differences. The phenotype is variable, and limited genotype phenotype correlation exists with SOS1 mutations often associated with normal cognition and stature, RAF1 mutations entailing a high HCM risk, and certain PTPN11 mutations predisposing to juvenile myelomonocytic leukemia. The recently identified SHOC2 mutation (p. Read More

Mol Syndromol 2013 Jun 8;4(5):227-34. Epub 2013 May 8.

Department of Pediatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Noonan syndrome (NS) is an autosomal dominant disorder characterized by facial dysmorphisms, short stature and congenital heart defects. The disorder is genetically heterogeneous and shows clinical overlap with other RASopathies. These syndromes are caused by mutations in a variety of genes leading to dysregulation of the RAS-MAPK pathway: PTPN11, KRAS, SOS1, RAF1, CBL, SHOC2, NRAS, BRAF, MAP2K1, MAP2K2, HRAS, NF1 and SPRED1. Read More

Semin Arthritis Rheum 2013 Oct 17;43(2):217-9. Epub 2013 Jun 17.

Department of Pediatric Immunology and Rheumatology, Necker enfants malades Hospital, Paris, France; INSERM U768, France; Imagine fundation, France. Electronic address:

Objective: RASopathies (Noonan syndrome (NS) and Noonan-related syndromes) are neurodevelopmental syndromes resulting from germline mutations in genes that participate in the rat sarcoma/mitogen-activated protein kinases (RAS/MAPK) pathway (PTPN11, SOS1, RAF, KRAS or NRAS, and SHOC2). Some monogenic conditions are associated with the development of systemic lupus erythematosus (SLE), and a few reports described the association of SLE with NS. We aim to search for a relationship between RASopathy and the development of SLE. Read More

J Clin Invest 2013 Apr 25;123(4):1556-70. Epub 2013 Mar 25.

Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

Genetic disorders of the Ras/MAPK pathway, termed RASopathies, produce numerous abnormalities, including cutaneous keratodermas. The desmosomal cadherin, desmoglein-1 (DSG1), promotes keratinocyte differentiation by attenuating MAPK/ERK signaling and is linked to striate palmoplantar keratoderma (SPPK). This raises the possibility that cutaneous defects associated with SPPK and RASopathies share certain molecular faults. Read More