LEOPARD syndrome: Clinical diagnosis in the first year of life
ABSTRACT LEOPARD syndrome (LS) is an autosomal dominant syndrome characterized by multiple lentigines and café-au-lait spots, electrocardiographic-conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormalities of the genitalia in males, retardation of growth, and deafness. LS shares many features with Noonan syndrome (NS), in which lentigines and deafness are usually not present. Molecular studies have shown that LS and NS are allelic disorders, caused by different missense mutations in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located at chromosome 12q22-qter. The clinical diagnosis of LS is generally difficult in the first months of life because the distinctive lentigines are generally not present at birth and develop during childhood. From January 2002 to December 2004, we suspected LS clinically in 10 patients admitted to our genetic counseling services in the first 12 months of life. A PTPN11 gene mutation was detected in 8/10 (80%) patients. In one patient without a PTPN11 mutation a subsequent clinical diagnosis of neurofibromatosis type 1 (NF1) was made, following the evaluation of the mother, who had previously undiagnosed classic NF1. The age of LS patients with PTPN11 mutation ranged between 1 and 11 months (mean age +/- SD 7.5 +/- 3.96 months). Review of the clinical characteristics of patients with LS confirmed by molecular study during the first year of life demonstrates that the diagnosis of LS in the first months of age can be clinically suspected in patients presenting with three main features, that is, characteristic facial features (100%), hypertrophic cardiomyopathy (HCM) (87%), and cafe-au-lait spots (75%). Characteristic facial features can be mild or severe, and consist of hypertelorism, downslanting palpebral fissures, ptosis, and dysmorphic ears. The clinical suspicion of LS may be confirmed by molecular screening for PTPN11 mutations. An early diagnosis of the disease is useful for the prospective care of associated medical problems and for precise genetic counseling.
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ABSTRACT: The RASopathies are a relatively common group of phenotypically similar and genetically related autosomal dominant genetic syndromes caused by missense mutations affecting genes participating in the RAS/mitogen-activated protein kinase (MAPK) pathway that include Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML, formerly LEOPARD syndrome). NS and NSML can be difficult to differentiate during infancy, but the presence of multiple lentigines, café au lait spots, and specific cardiac defects facilitate the diagnosis. Furthermore, individual PTPN11 missense mutations are highly specific to each syndrome and engender opposite biochemical alterations on the function of SHP-2, the protein product of that gene. Here, we report on a 5-year-old male with two de novo PTPN11 mutations in cis, c.1471C>T (p.Pro491Ser), and c.1492C>T (p.Arg498Trp), which are associated with NS and NSML, respectively. This boy's phenotype is intermediate between NS and NSML with facial dysmorphism, short stature, mild global developmental delay, pulmonic stenosis, and deafness but absence of café au lait spots or lentigines. The double-mutant SHP-2 was found to be catalytically impaired. This raises the question of whether clinical differences between NS and NSML can be ascribed solely to the relative SHP-2 catalytic activity. © 2014 Wiley Periodicals, Inc.American Journal of Medical Genetics Part A 09/2014; 164A(9). DOI:10.1002/ajmg.a.36620 · 2.05 Impact Factor
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ABSTRACT: Freckles, the lay term for ephelides and lentigines, are important pigmentation characteristics observed in humans. Both are affected by sunlight; ephelides are largely genetically determined but induced by sunlight whereas lentigines are induced by sun exposure and photodamage of the skin. However, despite being commonly observed, we know very little about them. Here we review the current status of knowledge about freckles and propose a model for their formation. This article is protected by copyright. All rights reserved.Pigment Cell & Melanoma Research 02/2014; DOI:10.1111/pcmr.12232 · 5.64 Impact Factor
Article: Peutz-Jeghers-Syndrom[Show abstract] [Hide abstract]
ABSTRACT: Die klinischen Zeichen eines Peutz-Jeghers-Syndroms gehen nicht selten in der Allgemeinversorgung unter. Die frühzeitige Diagnosestellung ist jedoch für die weitere Prognose maßgeblich. Hier ist es v. a. wichtig, nicht nur an die bekannte Manifestation der gastrointestinalen Polyposis zu denken, sondern auch an andere, die Prognose mitunter stark beeinflussende Prozesse wie die hier beschriebenen assoziierten Tumoren (z. B. Ovarial-, Hodentumoren) bei Vorliegen einer Mutation des Serin-Threonin-Kinase-Gens STK11 (Chromosom 19p13.3).Der Hautarzt 11/2012; 63(11). DOI:10.1007/s00105-012-2411-2 · 0.54 Impact Factor