Presentation
Central giant cell granulomas presenting as cyst-like lesions in the mandible have also been described in LEOPARD syndrome. [atlasgeneticsoncology.org]
Multiple dark lentigines (>10) and three larger café au lait spots were present. Both LEOPARD syndrome and neurofibromatosis-Noonan syndrome were considered in this child. No similar phenotype was present in the parents or her co-twin. [jmg.bmj.com]
The patient first presented for a cardiologic examination at the age of 3 months, due to a murmur. [degruyter.com]
Features of at least two other categories must be present. [jisppd.com]
Multiple lentigines syndrome should be considered in the differential diagnosis of multiple cafe au lait spots in children, particularly since the spots are usually present before the lentigines develop and may be clinically indistinguishable from the [scholars.northwestern.edu]
Entire Body System
- Short Stature
CONCLUSIONS: LEOPARD syndrome patients display distinctive features apart from multiple lentigines, such as a higher prevalence of hypertrophic cardiomyopathy and lower prevalence of short stature. [ncbi.nlm.nih.gov]
Noonan syndrome with multiple lentigines should be suspected in patients who demonstrate one or more of the following cardinal features: Lentigines Cardiac abnormalities Short stature Pectus deformity Facial dysmorphia. [dermnetnz.org]
- Multiple Congenital Anomalies
LEOPARD syndrome (LS), generally caused by heterozygous mutations in the PTPN11 gene, is a rare autosomal-dominant multiple congenital anomaly condition, characterized by skin, facial, and cardiac abnormalities. [ncbi.nlm.nih.gov]
LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. [perfusfind.com]
LEOPARD is multiple congenital anomaly syndrome inherited in an autosomal dominant manner with full penetrance and variable expressivity.1 Clinical diagnosis is based on multiple lentigines, typical facial features and cardiac anomalies. [rcpjournals.org]
Multiple LEOPARD syndrome is an autosomal dominant multiple congenital anomaly syndrome, with high penetrance and markedly variable expression. It was originally described by Gorlin as multiple lentigines syndrome. [academic.oup.com]
- Dentist
[…] syndrome can be unnoticed, the pediatric dentist can aid in the diagnostic process. 1. [jisppd.com]
The book will appeal to clinical geneticists, pediatricians, neurologists, head and neck surgeons, otolarynologists, and dentists. The 4th edition, which published in 2001, has sold 2,600 copies. [books.google.de]
Spec Care Dentist 9: 200–202. PubMed CrossRef Google Scholar Jóźwiak S, Schwartz RA, Krysicka-Janniger C, Zaremba J (1998) Familial occurrence of the LEOPARD syndrome. Int J Dermatol 37: 48–51. [link.springer.com]
[…] adults without heart disease on initial evaluation should have cardiac reevaluation every five years Dental Dental malocclusion Oral examination by primary care physician at each visit — Dental referral between one and two years of age, with annual dentist [aafp.org]
Respiratoric
- Pneumonia
Similar skin features were present in the father, a healthy man with a medical history of recurrent pneumonia and constipation during childhood. During childhood he had failed to thrive and had short stature. [jmg.bmj.com]
Gastrointestinal
- Failure to Thrive
She presented failure to thrive and psychomotor retardation, and was diagnosed with biventricular obstructive hypertrophic cardiomyopathy for which she had received high-dose beta-blocker therapy. [content.sciendo.com]
[…] syndrome Relevant diseases: Noonan syndrome Noonan syndrome plus other features Cardio-facio-cutaneous syndrome LEOPARD syndrome Costello syndrome Legius syndrome Inclusion criteria At least 2 of the suggestive clinical features: Early feeding difficulty/ failure [eastgenomics.org.uk]
Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity [aafp.org]
Congenital heart defects Skin abnormalities including rough skin and keratosis pilaris Failure to thrive Hypotonia Growth delays Three different genes have been found to be associated with CFC syndrome (BRAF, MEK1, MEK2), so genetic testing may be able [care.com]
Jaw & Teeth
- Prognathism
The patient also had pectus carinatum, ocular hypertelorism, and mandibular prognathism. Rosen 2 reported three siblings (two male and one female) with large numbers of lentigenes, but no mention was made of other disorders. [doi.org]
It was first reported by Zeisler and Becker in 1936, in a female patient presenting with multiple lentigines (increasing in number from birth to puberty), pectus carinatum, hypertelorism and prognathism.2 Around 200 patients have been reported worldwide [rcpjournals.org]
Approximately 75% have chest deformities, prognathism, scapula alata (protruding shoulder blade from the back), scoliosis (lateral curvation of the spine), or ankyloses of the spine. [hindawi.com]
Abnormalities also include: broad nasal root, prognathism (protruding lower jaw), or low-set, possibly rotated, ears. Pulmonary stenosis: Narrowing of the pulmonary artery as it exits the heart. [en.wikipedia.org]
Abnormalities also include: broad nasal root, prognathism (protruding lower jaw), or low-set, possibly rotated ears. [wikidoc.org]
- Dental Caries
The present case reported to the department with only history of dental caries and no existing relevant medical history. [jisppd.com]
Urs et al. recognized an interesting clinical characteristic, namely, the dental defects, in their patient and previously reported cases [6]. They presented the case of a 4-year-old male patient with the chief complaint of dental caries. [hindawi.com]
Eyes
- Prolapse
The propositus also had Gilbert's syndrome and mitral valve prolapse. No other family members personally examined had either of these last two disorders. [ncbi.nlm.nih.gov]
0008625 30%-79% of people have these symptoms Atrioventricular canal defect 0006695 Cryptorchidism Undescended testes Undescended testis [ more ] 0000028 Decreased fertility Abnormal fertility 0000144 Low-set, posteriorly rotated ears 0000368 Mitral valve prolapse [rarediseases.info.nih.gov]
Prolonged QTc Conduction defects Pulmonary valve stenosis Mitral valve prolapse Following are the less commonly heart related problems also observed: Coronary artery abnormalities, Atrial and atrioventricular septal defects, Apical aneurysm and non compaction [syndromespedia.com]
[…] features, other findings that can be associated with LEOPARD syndrome include pectus carinatum or excavatum, low-set ears, ptosis, abnormal dentition, and learning disabilities.3 Additional but less frequent cardiac abnormalities include mitral valve prolapse [consultant360.com]
Other cardiac abnormalities may be present, including aortic stenosis, or mitral valve prolapse. Abnormal genitalia Usually cryptorchidism (retention of testicles in body) or monorchism (single testicle). [wikidoc.org]
Ears
- Hearing Impairment
If individuals with NSML demonstrate hearing impairment, hearing aids may be beneficial. [rarediseases.org]
We report the case of a 12-year-old patient with some of the abovementioned characteristics: hypertelorism, macroglossia, lentigines, hypospadias, cryptorchidism, subaortic stenosis, growth retardation, and hearing impairment. [ncbi.nlm.nih.gov]
Musculoskeletal
- Winged Scapula
Some individuals with NSML may exhibit additional skeletal abnormalities such as unusually prominent shoulder blades (winged scapula), abnormal sideways curvature of the spine (scoliosis), and/or the development of abnormal front-to-back spinal curvature [rarediseases.org]
Skin
- Cafe-Au-Lait Spots
cafe au lait spots of neurofibromatosis. [scholars.northwestern.edu]
Noonan syndrome with cafe-au-lait spots and multiple lentigines syndrome are not linked to the neurofibromatosis type 1 locus. Clin Genet. 1995;48:85-9. [scielo.br]
Generalized lentiginosis is characteristic but they may not be present until age 4 or 5 years following the appearance of cafe-au-lait spots. Some patients have patchy scalp hair loss. [disorders.eyes.arizona.edu]
- Blister
PARALIZIE Bell Fibromul NONOSSIFYING benigne ( vezi fibrom ) Bifide cifre ( SEE POLYDACTILY ) BILIARĂ atrezie Muscaturi de artropode BLEPHAROPHIMOSIS si ptoza BLOODY scurgeri mamelonare în fază incipientă ( vezi Ectazia ductelor mamare ) BOHN nodul BLISTER [euro-libris.ro]
- Macula
All three patients presented with small dark-brown maculae on the face and neck and electrocardiographic abnormalities. [ncbi.nlm.nih.gov]
Lentigo or plural lentiginoza pigmented macula is a small, well circumscribed surrounded by normal-looking skin. Histologically includes hyperplasia of epidermis and increased basal layer pigmentation. [medicaldb.blogspot.com]
Face, Head & Neck
- Hypertelorism
Patient’s face (front view), showing lentigines, hypertelorism, and tongue protrusion. B. [scielo.br]
Ocular hypertelorism with a wide nasal bridge and thick averted lips were noticeable [Figure 1] and [Figure 2]. [jisppd.com]
D: deafness (sensorineural) Importantly, this acronym does not include the other craniofacial anomalies (in addition to hypertelorism) which are identical to those of Noonan syndrome and present in nearly all patients 5. [radiopaedia.org]
He had numerous pinhead to pea sized, dark brownish macules scattered on the entire body and also had pulmonary stenosis, EKG abnormality, ocular hypertelorism and right exotropia. [synapse.koreamed.org]
Complex comprising multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, sensorineural deafness, and autosomal dominant hereditary pattern. [altmeyers.org]
- Mandibular Prognathism
The patient also had pectus carinatum, ocular hypertelorism, and mandibular prognathism. Rosen 2 reported three siblings (two male and one female) with large numbers of lentigenes, but no mention was made of other disorders. [doi.org]
Other findings include the following: Mandibular prognathism. [jisppd.com]
prognathism, winging of the scapulae, scoliosis, joint hyper flexibility and other findings are less common. [e-ijd.org]
Bone abnormality The following bone or skeletal system abnormalities are observed in LEOPARD Syndrome; Wide chest Pectus carinatum (protrusion of the sternum and ribs) Excavatum (sunken sternum) Mandibular prognathism or protruding jaw Winging of the [syndromespedia.com]
prognathism Broad nasal root Dysmorphic skull Low-set ears High palate arch Epicanthal folds Ptosis Corneal tumors Other skeletal abnormalities: Pectus excavatum or carinatum Kyphoscoliosis or winging of scapulae Syndactyly Delayed development or agenesis [5minuteconsult.com]
- Thick Lips
In addition to ocular hypertelorism, affected individuals may have droopy eyelids (ptosis), thick lips, and low-set ears. [medlineplus.gov]
In addition to ocular hypertelorism, affected individuals may have droopy eyelids ( ptosis ), thick lips, and low-set ears. [ghr.nlm.nih.gov]
The child has developed multiple distinct Dysmorphic features with increasing of age, which include: Hypertelorism: orbits are distantly apart from each other Flat nasal bridge Dysmorphic ears Low-set ears Thick lips Drooping or falling of the upper eyelid [syndromespedia.com]
Ocular hypertelorism addition, affected individuals may have ptosis, thick lips and low - set ears. The incidence of this anomaly is unknown, but is believed to be underdiagnosed, especially milder and / or absence of lentiginosis cases. [ivami.com]
- Short Neck
neck Decreased length of neck 0000470 Short stature Decreased body height Small stature [ more ] 0004322 Strabismus Cross-eyed Squint Squint eyes [ more ] 0000486 Subvalvular aortic stenosis Narrowing of blood vessel below aortic heart valve 0001682 [rarediseases.info.nih.gov]
Other features shared between the two conditions include short stature, intellectual disability, lax joints, and head/neck features such as a highly arched palate, a short neck, a large forehead, and low-set ears. [forgottendiseases.org]
[…] a small jaw a short neck with excess skin folds a lower-than-usual hairline at the back of the head and neck Children with Noonan syndrome also have abnormalities that affect the bones of the chest. [nhs.uk]
Physical examination revealed facial dysmorphism, including an inverted triangular-shaped face, short neck, large low-set ears, orbital hypertelorism, megalocornea, and pectus excavatum. [actasdermo.org]
Ocular hypertelorism, down-slanting palpebral fissures, ptosis, blue–green irides, short nose with a wide base and depressed nasal bridge, low-set and posteriorly angulated ears with thick helices, micrognathia, short neck with excessive nuchal skin and [nature.com]
- Broad Nasal Bridge
In addition, there was mild facial dysmorphia including hypertelorism, low-set ears and broad nasal bridge. Her mother showed a similar facial appearance and a larger number of lentigines on her trunk and face. [ijdvl.com]
bridge Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal [rarediseases.info.nih.gov]
Workup
A small number of patients with LEOPARD syndrome had an extensive cardiac workup using invasive and noninvasive techniques. [ajronline.org]
The radiologic and laboratory workups revealed certain notable findings. The dental roots were abnormal or absent in some positions, as seen on the radiograph. [hindawi.com]
Vascular workup The patient's apparently aggressive aneurysmal disease prompted a thorough investigation. Widespread disease was found, predominantly in the peripheral vessels. [jvascsurg.org]
Blocks
- First-Degree Atrioventricular Block
Electrocardiography showed a first-degree atrioventricular block, whereas heart ultrasound evaluation did not find any valve abnormality. Hearing investigations confirmed sensorineural deafness. [jamanetwork.com]
Treatment
Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]
Treatment beta-blockade or calcium channel blockers are most frequently used in treatment of obstructive cardiomyopathy. If there is no response to drug therapy, surgery for left ventricular outflow obstruction or transplantation can be indicated. [atlasgeneticsoncology.org]
Treatment response to intravenous immunoglobulins was excellent. In patients with LEOPARD syndrome and acute neuropathies, treatment with intravenous immunoglobulins should be considered. [ncbi.nlm.nih.gov]
An ideal treatment would be to use a hearing aid. Hormonal treatment would be needed at the expected time of puberty. Laser or bleaching creams helps in lightening of the brown spots. [medicalpicturesinfo.com]
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. [pennstatehershey.adam.com]
Prognosis
Prognosis The prognosis is mainly determined by the nature and severity of cardiac lesions. In fact, the major concern is that of hypertrophic cardiomyopathy, because of its association with arrhythmia and sudden death. [atlasgeneticsoncology.org]
Prognosis appears to be related to the type of structural, myocardial, and arrhythmogenic cardiac disease, especially hypertrophic cardiomyopathy (HCM). [ncbi.nlm.nih.gov]
Etiology
Moreover, using phoshoproteomics we show hypo- and hypertyrosyl phosphorylation of Fer kinase and PZR (Protein zero related), respectively and study their roles as (potential) interacting proteins in the etiology of both NS and LS. [scholarlypublications.universiteitleiden.nl]
In this case report we describe these anomalies and discuss the relationship between them and the proposed etiology of the disease. [ncbi.nlm.nih.gov]
Epidemiology
Zeisler and Becker, 1936; Moynahan, 1962; Gorlin (acronym: LEOPARD), 1969 You might also be interested in Dermatology Occurrence/Epidemiology This section has been translated automatically. [altmeyers.org]
No epidemiologic data are available on the real incidence of LEOPARD syndrome; however, this seems to be a rare disease, being often underdiagnosed, as many of its features are mild. [content.sciendo.com]
Noonan syndrome is fairly common, affecting 1:1000 to 1:2500 live births, Neurofibromatosis 1 (once thought to be related to Leopard syndrome) is also common affecting 1 in 3500 individuals, however no epidemiologic data exists for Leopard syndrome.[2 [bionity.com]
Chapters on epidemiology, embryology, non-syndromic hearing loss, and syndromic forms of hearing loss have all been updated with particular attention to the vast amount of new information on molecular mechanisms, and chapters on clinical and molecular [books.google.de]
Pathophysiology
Enhanced PZR-mediated membrane recruitment of Shp2 serves as a common mechanism to direct overlapping pathophysiological characteristics of these PTPN11 mutations. Copyright © 2014, American Society for Microbiology. All Rights Reserved. [ncbi.nlm.nih.gov]
Pathophysiology Mutation in the stem cell pool of the neural crest in embryonic life is regarded as a common cause of cutaneous (producing lentigines), neurologic, cardiac (resulting in cardiomyopathy), and possibly urogenital defects. [accessanesthesiology.mhmedical.com]
Etiology and Pathophysiology LEOPARD syndrome and a related disorder, Noonan syndrome (NS), are allelic disorders resulting from different missense mutations. 90% of these mutations are in the PTPN11 gene. [5minuteconsult.com]
Although treatment algorithms are similar between LS patients with ventricular hypertrophy and patients with familial HCM, without an evidence-based diagnosis, despite their analogous character it is clear that the pathophysiology and dynamics of HCM [revespcardiol.org]
Etiology and Pathophysiology In most individuals, NSML and Noonan syndrome (NS) are allelic disorders resulting from different missense mutations. 90% of these mutations are in the PTPN11 gene. [unboundmedicine.com]
Prevention
1 Department of Pedodontics and Preventive Dentistry, Krishnadevaraya College of Dental Sciences and Hospital, Bangalore, Karnataka, India 2 Department of Pedodontics and Preventive Dentistry, A.E.C.S Maaruti College of Dental Science and Research Centre [jisppd.com]
He had recurrent upper extremity aneurysms requiring multiple operations and finally PTFE reinforced venous grafts to prevent further aneurysmal degeneration. He has multiple other peripheral aneurysms, thus far asymptomatic. [ncbi.nlm.nih.gov]