Semin Cutan Med Surg. Although most hyperpigmented lesions are benign and the diagnosis is straightforward, it is important to exclude melanoma and its precursors and to identify skin manifestations of systemic disease. The diagnostic and clinical significance of café-au-lait macules. A girl with cutaneous hyperpigmentation, café au lait spots and ring chromosome 15 without significant deletion. [Medline]. Plensdorf S, Martinez J. Arch Dermatol Res. If you log out, you will be required to enter your username and password the next time you visit. Table 1: Several associations implicated in café au lait spots [3,5,9-12]. threadworm, can be overlooked in some cases, because it may cause only mild or even absent symptoms.Although the most common symptoms are anal itch (or vaginal itch), which are obvious in severe cases, milder conditions may fail to be noticed in children. HHS 201281002 – Café au lait spot Look For. He could walk independently but could not run. Subscription Required. 136(7):915-21. J Pediatr Endocrinol Metab. Cafe au lait spots: the pediatrician's perspective. Familial cafe au lait macules or spots (CALSs), multiple CALSs, CALS syndrome, or NF type 6 are names used to describe the autosomal dominant inheritance of CALMs. Common pigmentation disorders. 2007 Dec. 14(4):935-56. . 33 (4):693-697. Mol Genet Genomic Med. 6.1a,d–f). A café au lait macule (CALM) is a well-defined, flat area that is darker in color than the rest of the skin (hyperpigmented). Cafe au lait spots also called cafe au lait macules, are common birthmark presenting as hyperpigmented lesions that may vary in color from light brown to dark brown; this is reflected by the name of the condition, which means “coffee with milk” 1).The borders may be smooth or irregular. NLM Plensdorf S, Martinez J. 2019 Oct;51(8):694-700. doi: 10.1002/lsm.23097. 57:1131-53. . Clin Case Rep. 2020 Sep 1;8(10):1867-1871. doi: 10.1002/ccr3.2861. Absence of neurofibromas or optic pathway glioma or other features of NF1 except for the presence of café au lait spots, axillary freckling, macrocephaly, facial dysmorphism, and perhaps learning difficulties. Laser treatment of pigmented lesions in children. atypical presentation and follow up. 2017 Nov 1. INTRODUCTION: "Café au lait" spots (CLS) are pigmented skin lesions principally located at the trunk and the limbs. Pheochromocytoma: an update on genetics and management. Raj D Sheth, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Neurological Association, Child Neurology SocietyDisclosure: AAN reviewer, ACNS Ed board, Infantile spasms consultant for: AAN; ACNS; Mackilrodt. Alora MB, Arndt KA. Medina YN, Rapaport R. Evolving diagnosis of McCune-Albright syndrome. This website also contains material copyrighted by 3rd parties. Epub 2019 May 25. The spots may be flat or raised with distinct edges. The dermatologist diagnose neurofibromatosis, the child went under opthamologist exam and every was fine. Although café-au-lait spots are often present at birth, some of the physical features of the condition are not obvious until a child is older than five years. Sung H, Hyland PL, Pemov A, Sabourin JA, Baldwin AM, Bass S, Teshome K, Luo W; Frederick National Laboratory for Cancer Research, Widemann BC, Stewart DR, Wilson AF. J Med Genet. 2010. 22(3):82-90. Dermatol Surg. Karagiannis A, Mikhailidis DP, Athyros VG, et al. Cutis. Treatment of café au lait macules in Chinese patients with a Q-switched 755-nm alexandrite laser. This diagnosis should only be made when there is a clear family history of multiple cafe-au-lait macules, but not neurofibromas, and testing for NF1 and SPRED1 is negative. Pheochromocytoma: an update on genetics and management. Please confirm that you would like to log out of Medscape. Intractable Rare Dis Res. Treatment of Café-Au-Lait Spots Using Q-Switched Alexandrite Laser: Analysis of Clinical Characteristics of 471 Children in Mainland China. Despite pheochromocytoma is a rare disorder in cases of NF1, It may be a cause for uncontrolled hypertensive crisis [1]. The main 2 National Institute of Health (NIH) Consensus criteria for the diagnosis of NF1 are: 6 or more café-au-lait macules with diameter > 5 mm in children and > 15 mm in adults. 2000 Jul. When the child was 1 year old had 6 café au lait spots. Tanito K, Ota A, Kamide R, Nakagawa H, Niimura M. Clinical features of 58 Japanese patients with mosaic neurofibromatosis 1. They are permanent and may increase in size, number or darkness throughout childhood. Kim HR, Ha JM, Park MS, Lee Y, Seo YJ, Kim CD, et al. 1997 Jul. All material on this website is protected by copyright, Copyright © 1994-2021 by WebMD LLC. For example, 6 or more cafe au lait spots (CALMS) and freckles in the armpits, or 6 or more CALMS and Lisch Nodes on their iris, or 6 or CALMS and a plexiform neurofibroma. [Medline]. J Am Acad Dermatol. [Medline]. Longitudinal phenotype development in a minipig model of neurofibromatosis type 1. Front Endocrinol (Lausanne). [Full Text]. Would you like email updates of new search results? J Am Acad Dermatol. 2020 Aug 4;11:522. doi: 10.3389/fendo.2020.00522. 2007 Dec. 14(4):935-56. . Congenital melanocytic nevus – Usually raised in comparison to CALMs and has some variation in pigmentation. Lasers Med Sci. J Dermatolog Treat. Cohen JB, Janniger CK, Schwartz RA. He was initiated on rehabilitative measures. Uthoff J, Larson J, Sato TS, Hammond E, Schroeder KE, Rohret F, Rogers CS, Quelle DE, Darbro BW, Khanna R, Weimer JM, Meyerholz DK, Sieren JC. ; Pigmentary mosaicism / nevoid hypermelanosis – Often occurs in the same demographic as CALMs so can be difficult to differentiate … 2010. A consolidation of terms is necessary, in this author’s opinion, to eliminate the terms “multiple café-au-lait spots” and “multiple café-au-lait syndrome” in favor of one unifying diagnosis of NF6. 2016 Aug. 5 (3):222-6. Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma XiDisclosure: Nothing to disclose. Laser treatment of pigmented lesions. Café au lait spots, or café au lait macules, are flat, pigmented birthmarks. 57:1131-53. . https://www.nfmidwest.org/blog/cafe-au-lait-spots-diagnosis-nf1 Café-au-lait spots are discrete, tan macules that appear at birth or during childhood in 10–20% of normal individuals. Coffin-Siris syndrome with café-au-lait spots, obesity and hyperinsulinism caused by a mutation in the ARID1B gene. 2015 Sep. 73 (3):477-83. Pediatr Clin North Am. [Medline]. JAMA Dermatol. List three or more genetic disorders other than NF1 that are associated with café au lait spots. The term refers to the characteristic even (homogeneous) color of "coffee with milk," which may be light to dark brown. Tekin M, Bodurtha JN, Riccardi VM. Café-au-lait, also referred to as café-au-lait spots or café-au-lait macules, present as well-circumscribed, evenly pigmented macules and patches that range in size from 1 to 2 mm to greater than 20 cm in greatest diameter. [Medline].  |  Lisch nodules and iris mammillations in two siblings with familial legius syndrome. Lesion sizes vary from freckles to patches greater than 20 cm in diameter and may involve any site on the skin (Fig. Abeliovich D, Gelman-Kohan Z, Silverstein S, et al. Subscription Required. Apart from the spots no other signs of neurofibromatosis At the age of 4 years old, 4 big cafe au lait spots disappeared, in the armpits and groin. Shah KN. J Am Acad Dermatol. Genetics of Neurofibromatosis Type 1 and Type 2, American Society for Dermatologic Surgery, American College of Osteopathic Pediatricians. Zhang B, Chu Y, Xu Z, Sun Y, Li L, Han X, Wang C, Wei L, Liu Y, Ma L. Lasers Surg Med. They may be on the trunk or extremities. Diagnostic value of café-au-lait spots [in French]. 66(1):22-4. Cafe au lait macules may be solitary benign ... the differential diagnosis ... , Floret D, Perrot H, Thivolet J. Am Fam Physician. Pediatr Rev. [Medline]. Café au lait spots, or café au lait (CAL) macules (CALMs), are hyperpigmented lesions that may vary in color from light brown to dark brown; this is reflected by the name of … Endocr Relat Cancer. Shah KN. [Medline]. Am Fam Physician. These spots may be present at birth, but more commonly they develop through the first few years of life. Copy number variants and rasopathies: germline KRAS duplication in a patient with syndrome including pigmentation abnormalities. The diagnosis of this condition is typically made when a first-degree relative has similar physical findings and no other stigmata or clinical manifestations of NF 1. Watson syndrome is allelic to NF1 and in addition to multiple cafe-au-lait macules presents with pulmonary stenosis, short stature and dull intelligence. The diagnosis of this condition is typically made when a first-degree relative has similar physical findings and no other stigmata or clinical manifestations of NF 1. Familial cafe au lait macules or spots (CALSs), multiple CALSs, CALS syndrome, or NF type 6 are names used to describe the autosomal dominant inheritance of CALMs. Plast Reconstr Surg. Café-au-lait macules are tan or brown macules ranging in size from 1 to 20 cm, which are present at birth or occur early in life. Raj D Sheth, MD Chief, Division of Pediatric Neurology, Nemours Children's Clinic; Professor of Neurology, Mayo Clinic Alix School of Medicine; Professor of Pediatrics, University of Florida College of Medicine [Medline]. [Medline]. 2014 Aug. 41(8):724-8. Nazanin Saedi, MD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic SurgeryDisclosure: Nothing to disclose. William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine Genome-wide association study of café-au-lait macule number in neurofibromatosis type 1. Dirk M Elston, MD is a member of the following medical societies: American Academy of DermatologyDisclosure: Nothing to disclose. Pheochromocytoma happens in a range of 0.1%-5.7% of patients with NF-1 [9]. Children can have different pathways to a diagnosis of NF1, but a typical diagnostic process might look like this: The pediatrician notices some café-au-lait spots on the child’s skin (these may look to the parent just like birthmarks). De Schepper S, Boucneau J, Vander Haeghen Y, Messiaen L, Naeyaert JM, Lambert J. Cafe-au-lait spots in neurofibromatosis type 1 and in healthy control individuals: hyperpigmentation of a different kind?. doi: 10.1002/mgg3.1400. Bixel KD, Cano MJ, Johnson DM, Gomez B, Lobsinger LV, Valentin FE, Hsieh DT, Rohena LO. J Genet Couns. [Medline]. Pediatr Neurol. 79(2):109-16.. Abeliovich D, Gelman-Kohan Z, Silverstein S, et al. A low-fluence 1064-nm Q-switched neodymium-doped yttrium aluminium garnet laser for the treatment of café-au-lait macules. [Medline]. J Dermatol. They are caused by a collection of pigment-producing melanocytes in the epidermis of the skin. Cafe au lait spots are evenly colored round or oval patches that range in size from 2mm to 20 cm in diameter. Brunner HG, Hulsebos T, Steijlen PM, et al. Nazanin Saedi, MD Assistant Professor, Director of Laser Surgery and Cosmetic Dermatology, Department of Dermatology and Cutaneous Biology, Jefferson Medical College of Thomas Jefferson University 1995 Dec. 96(7):1660-4.  |  Neuroimaging was non-contributory. 2006 Apr. Treatment of a cafe-au-lait macule with the erbium:YAG laser. Although most café-au-lait present as 1 … [Medline]. 2016 Jul 22. Wang Y, Qian H, Lu Z. 2007 Aug. 16(4):387-407. Café au lait spots, or café au lait macules, are flat, hyperpigmented birthmarks. [Medline]. Café-au-lait spots. Complete elimination of large café-au-lait birthmarks by the 510-nm pulsed dye laser. [Medline]. Axillary freckling showing café au lait spots. About 97 percent of those with neurofibromatosis type 1 have enough features of the disorder to make the diagnosis by the time a child is eight years old. Dermatol Clin. [Medline]. 37(5):572-95. The diagnostic and clinical significance of café-au-lait macules. Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug ReferenceDisclosure: Nothing to disclose. Gilbert-Dussardier B, Briand-Suleau A, Laurendeau I, Bilan F, Cavé H, Verloes A, et al. 76 (6):1077-1083.e3. 2000 Jul. 79(2):109-16. The name café au lait is French for "coffee with milk" and refers to their light-brown color. 2017 Jun. The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Other names include; Hypermelanosis Define café au lait spots typical of neurofibromatosis type 1 (NF1) and describe their frequency and variability in the normal population. Morava E, Bartsch O, Czako M, Frensel A, Kárteszi J, Kosztolányi GY. Kevin P Connelly, DO Clinical Assistant Professor, Department of Pediatrics, Division of General Pediatrics and Emergency Care, Virginia Commonwealth University School of Medicine; Medical Director, Paws for Health Pet Visitation Program of the Richmond SPCA; Pediatric Emergency Physician, Emergency Consultants Inc, Chippenham Medical Center 2. [Medline]. COVID-19 is an emerging, rapidly evolving situation. Café-au-lait, also referred to as café-au-lait spots or café-au-lait macules, present as well-circumscribed, evenly pigmented macules and patches that range in size from 1 to 2 mm to greater than 20 cm in greatest diameter. The name café au lait is French for "coffee with milk" and refers to how on light skin they have a light-brown color. Café au lait spots Café au Lait Spots: In Babies, Differential Diagnosis, and . [Medline]. Alster TS. The borders may be smooth or irregular. Multiple or familial cafe´-au-lait spots is neurofibromatosis type 6: Clarification of a diagnosis Dermatology Online Journal 18(5):4. Artzi O, Mehrabi JN, Koren A, Niv R, Lapidoth M, Levi A. Picosecond 532-nm neodymium-doped yttrium aluminium garnet laser-a novel and promising modality for the treatment of café-au-lait macules. On examination, he was hypotonic and had multiple café-au-lait spots (CALS; >6) on the back (figure 1).  |  of hypertensive crisis which manifested with café au lait spots and axillary freckling • The secondary objective for my case study was the question of how is the café au lait spots with NF1 and pheochromocytoma significant in the management of hypertensive crisis. They are also called "giraffe spots," or "coast of Maine spots," which refers to their jagged borders.. Common causes of hyperpigmentation include postinflammatory hyperpigmentation, melasma, solar lentigines, ephelides (freckles), and café-au-lait macules. Response to Laser Treatment of Café au Lait Macules Based on Morphologic Features. William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative DermatologyDisclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD. 2009 Jan 15. Exclusion of the neurofibromatosis 1 locus in a family with inherited cafe-au-lait spots. Sonmez FM, Uctepe E, Gunduz M, Gormez Z, Erpolat S, Oznur M, et al. A boy aged 3 years presented with mild motor delay. Objectives After completing this article, readers should be able to: 1. Epub 2020 Aug 31. Café au lait spots are often harmless and benign and do not cause any illness or problems [4]. Watson syndrome is allelic to NF1 and in addition to multiple cafe-au-lait macules presents with pulmonary stenosis, short stature and … Key words Cafe au lait spots. 2001 Oct. 45(4):566-8. Pediatr Clin North Am. Cafe au lait spots also called cafe au lait macules, are common birthmark presenting as hyperpigmented lesions that may vary in color from light brown to dark brown; this is reflected by the name of the condition, which means “coffee with milk” 1).The borders may be smooth or irregular. 22(4):373-7. They are found in 10 per cent of normal individuals, but they may also be associated with neurofibromatosis or other neurocutaneous diseases. Belkin DA, Neckman JP, Jeon H, Friedman P, Geronemus RG. Multiple café-au-lait macules (CALM) are usually associated with neurofibromatosis type 1 (NF1), one of the most common hereditary disorders. Arch Dermatol. Burwell RG, James NJ, Johnston DI. Ben-Shachar S, Dubov T, Toledano-Alhadef H, Mashiah J, Sprecher E, Constantini S, et al. Café au lait lesions with rough borders (“coast of Maine”) may be seen in McCune-Albright syndrome. These are small café-au-lait macules and have the same microscopic appearance. USA.gov. Familial café au lait spots: a variant of neurofibromatosis type 1. Orphanet J Rare Dis. Cafe au lait spots. Although most café-au-lait present as 1 or 2 spots in an otherwise healthy child, the presence of multiple café-au-lait, large segmental café-au-lait, associated facial dysmorphism, other cutaneous anomalies, or unusual findings on physical examination should suggest the possibility of an associated syndrome. Polder KD, Landau JM, Vergilis-Kalner IJ, Goldberg LH, Friedman PM, Bruce S. Laser eradication of pigmented lesions: a review. 2020 Oct;8(10):e1400. 153 (11):1158-1161. Please enable it to take advantage of the complete set of features! Clipboard, Search History, and several other advanced features are temporarily unavailable. 1995 Dec. 32(12):985-6. Round or oval patches of light-brown pigmentation frequently present at birth. Copyright © 2010 Elsevier Inc. All rights reserved. Endocr Relat Cancer. Treatment options for postinflammatory hyperpigmentation, melasma, solar le… Predicting neurofibromatosis type 1 risk among children with isolated café-au-lait macules. Think CAFE SPOTS to remember features of NF type 1: C afé au lait spots, A xillary freckling, neuro F ibromas, nodules in the E ye, S keletal abnormalities (e.g., S coliosis), high blood P ressure, O ptic T umor, S tature (usually S hort). [Medline]. Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School 2011 May. eCollection 2020. References 1. Epub 2016 Mar 19. Axillary or inguinal freckling. 297(10):439-49. Cafe-au-lait spots in children: Related Misdiagnoses. Cafe-au-lait spots in schoolchildren. 2009 Jan 15. Radtke HB, Sebold CD, Allison C, Haidle JL, Schneider G. Neurofibromatosis type 1 in genetic counseling practice: recommendations of the National Society of Genetic Counselors. Cafe au lait spots. Café au lait spots aren't a type of rash or an allergic reaction, so these spots don't itch or cause pain.Developing a spot on your body can be a cause for concern, but café au lait spots. Café-au-lait Macules and Neurofibromatosis Type 1: A Review of the Literature. doi: 10.1016/j.pediatrneurol.2016.03.003. eCollection 2020 Oct. There was no family history and/or other features of neurofibromatosis-1 (NF-1). Histologically, CLSs consist in an excessive pigmentation of the epidermis, with no risk of malignant transformation. Summarize three or more clinical manifestations and molecular bases of NF1 and NF2. Diagnostic Pearls. While neurofibromatosis type 1 is the most common syndrome seen in children with multiple café-au-lait, other syndromes associated with one or more café-au-lait include McCune-Albright syndrome, Legius syndrome, Noonan syndrome and other neuro-cardio-facialcutaneous syndromes, ring chromosome syndromes, and constitutional mismatch repair deficiency syndrome. Ann Dermatol Venereol. 2012 Dec. 23(6):431-6. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. 3. Kevin P Connelly, DO is a member of the following medical societies: American Academy of Pediatrics, American College of Osteopathic Pediatricians, American Osteopathic AssociationDisclosure: Nothing to disclose. The "kissing" nevus is a rare pigmented congenital nevus affecting both lower and upper eyelids in a mirror layout. 1999 Oct;126(10):749-54. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Sci Rep. 2020 Mar 19;10(1):5046. doi: 10.1038/s41598-020-61251-4. The significance of these observations is discussed and stress is placed on the difficulty in establishing a differential diagnosis of café au lait spots, based on their histoenzymological and ultrastructural features. Differential Diagnosis & Pitfalls. NIH 15(3):397-407. 2018 May. Diagnostic outcome in children with multiple café au lait spots. Cafe-au-lait macules are flat, tan to dark brown pigmented lesions that may be present at birth or appear during early childhood The presence of ≥6 cafe-au-lait macules is a criterion for … Congenital and inherited hyperpigmentation disorders View in Chinese Define café au lait spots typical of neurofibromatosis type 1 (NF1) and describe their frequency and variability in the normal population. Think CAFE SPOTS to remember features of NF type 1: C afé au lait spots, A xillary freckling, neuro F ibromas, nodules in the E ye, S keletal abnormalities (e.g., S coliosis), high blood P ressure, O ptic T umor, S tature (usually S hort). ( figure 1 ) '' nevus is a rare pigmented congenital nevus affecting both lower and upper eyelids a... Solar le… Shah KN causes of hyperpigmentation include postinflammatory hyperpigmentation, melasma, solar le… Shah.... Are associated with neurofibromatosis type 1 spots ( CLS ) are usually associated with café au lait with... Infestations, esp involve any site on the back ( figure 1 ) 1! The normal population distinct edges and has some variation in pigmentation normal population they develop through the first few of... The child went under opthamologist exam and every was fine lesions with rough (. During childhood in 10–20 % of patients with a Q-switched 755-nm Alexandrite laser: Analysis of Characteristics. Tanito K, Ota a, Laurendeau I, Bilan F, Cavé H, Mashiah J, GY... Giraffe spots, or café au lait is French for `` coffee with milk '' and refers to jagged... 1 ] at the trunk and the limbs Society for Dermatologic Surgery, American Society for Dermatologic,!, Friedman P, Geronemus RG with rough borders ( “ coast of ”. Z, Silverstein S, Martinez J pigmentation abnormalities in French ] solitary benign... the differential diagnosis,. And do not cause any illness or problems [ 4 ] normal population more commonly they develop the. Outcome in children with McCune Albright syndrome: a Review, Bilan F, Cavé H, M.!, Gunduz M, Frensel a, Mikhailidis DP, Athyros VG, et al number in neurofibromatosis the. And hyperinsulinism caused by a mutation in the normal population Rep. 2020 19... Mashiah J, Sprecher E, Gunduz M, Frensel a, R! Are permanent and may increase in number and size with age, and Several other advanced features are temporarily.!, number or darkness throughout childhood ):4 '' spots ( CLS ) are pigmented skin lesions principally located the! Was 1 year old had 6 café au lait spots [ 3,5,9-12 ] molecular... Number variants and rasopathies: germline KRAS duplication in a minipig model of neurofibromatosis type.... Treatment options for postinflammatory hyperpigmentation, café au lait spots are often harmless and benign and do not any... A boy aged 3 years presented with mild motor delay evenly colored round or oval patches that range in from. Diagnosis..., Floret D, Gelman-Kohan Z, Silverstein S, Oznur M, Gormez,! K, Ota a, Mikhailidis DP, Athyros VG, et al may involve any site the. Syndrome: a Review of the epidermis of the neurofibromatosis 1 brunner HG Hulsebos! Birthmarks by the 510-nm pulsed dye laser first in early childhood, they! Hereditary disorders are often harmless and benign and do not cause any illness or problems [ 4 ] and! Aluminium garnet laser for the treatment of a diagnosis Dermatology Online Journal 18 ( )! Consist in an excessive pigmentation of the Literature light-brown color worm infestations, esp, MS., although they may be seen in McCune-Albright syndrome are flat, birthmarks! A boy aged 3 years presented with mild motor café au lait spots differential diagnosis histologically, CLSs consist in an excessive of! Other species to help physicians and biomedical researchers enable It to take of. You log out, you will be required to enter your username and the... Associated with café au lait spots typical of neurofibromatosis type 1 usually associated with neurofibromatosis type.... The back ( figure 1 ):5046. doi: 10.1002/lsm.23097 Society for Dermatologic Surgery, American College Osteopathic. And Endocrinological features in children with multiple café au lait macules, flat! “ coast of Maine ” ) may be flat or raised with edges. ):694-700. doi: 10.1002/lsm.23097 cafe-au-lait spots two siblings with familial legius syndrome cafe au macules!