Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I (NF-1). It is caused by mutations in the SPRED1 gene. It is also known as neurofibromatosis type 1-like syndrome (NFLS). Symptoms and signs
Nearly all individuals with Legius syndrome show multiple café au lait spots on their skin. Symptoms may include:
Freckles in the axillary and inguinal skin fold
Lipomas, developing in adulthood
Macrocephaly
Learning disabilities
ADHD
Developmental delayFeatures common in neurofibromatosis – like Lisch nodules (iris hamartomas diagnosed on slit lamp exam), bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors – are absent in Legius syndrome. Cause
Legius syndrome is a phakomatosis and a RASopathy, a developmental syndrome due to germline mutations in genes. The condition is autosomal dominant in regards to inheritance and caused by mutations to the SPRED1 gene at chromosome 15, specifically 15q14 (or (GRCh38): 15:38,252,086-38,357,248). The gene in question demonstrates almost 100 mutations. Mechanism
A mutated SPRED1 protein adversely regulates Ras-MAPK signaling, which is a chain of proteins in a cell that sends signals from the surface of a cell to the nucleus which in turn causes the symptoms of this condition. Diagnosis
Genetic testing is necessary to identify the syndrome. The DNA test is necessary sometimes, because symptoms may not be sufficient to definitely diagnose this condition.
The alveoli still appear consolidated, but grossly the color is paler and the cut surface is drier. This is when death typically occurs in severe cases. Resolution (complete recovery): The exudate is digested by enzymatic activity, and cleared by macrophages or by cough mechanism. Enzymes produced by neutrophils will liquify exudates, and this will either be coughed up in sputum or be drained via lymph. In children
The openings between the alveoli known as the pores of Kohn, and the collateral airways of the canals of Lambert, are undeveloped in children. Spread of infection that would otherwise occur is prevented and can result in round pneumonia, most commonly caused by S. pneumoniae. This clinically presents with an initial mild respiratory infection, followed by fever. On imaging it presents an opaque pulmonary consolidation which is unusually round, and can resemble a lung mass. However it quickly resolves with antibiotics. Diagnosis
The most common organisms which cause lobar pneumonia are Streptococcus pneumoniae, also called pneumococcus, Haemophilus influenzae and Moraxella catarrhalis. Mycobacterium tuberculosis, the tubercle bacillus, may also cause lobar pneumonia if pulmonary tuberculosis is not treated promptly. Other organisms that cause lobar pneumonia are Legionella pneumophila and Klebsiella pneumoniae.Like other types of pneumonia, lobar pneumonia can present as community acquired, in immune suppressed patients or as nosocomial infection. However, most causative organisms are of the community acquired type.