Legius syndrome

Legius syndrome
Classification and external resources
OMIM	611431
DiseasesDB	34916

Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots.^[1] 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.^[2]^[3]^[4] It is also known as Neurofibromatosis Type 1-like syndrome (NFLS). The syndrome is named after Eric Legius, Professor at the KU Leuven. It is a RASopathy.

Symptoms

Nearly all patients show multiple Café au lait spots. Other symptoms may include:

Freckles in the armpits and/or groin
Lipomas
Macrocephaly
Learning disabilities
ADHD
Developmental delay^[5]

Features common in neurofibromatosis - Lisch nodules, bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumors - are absent in this condition.

Diagnosis

Genetic testing is necessary to identify the syndrome. The test checks for loss of function mutations in the SPRED1 gene.

Confusion with Neurofibromatosis Type I

The symptoms of Legius syndrome and NF-1 are very similar. This is the reason why the two are easily confused. A genetic test is often the only way to make sure a person has LS and not NF-1. The similarity of symptoms stem from the fact that the different genes affected in the two syndromes code for proteins that carry out a similar task in the same reaction pathway.

An important difference is the absence of tumor growths (Lisch nodules and Neurofibromas which are common in NF-1) in LS.^[5]

Because of this difference, Legius syndrome is often seen as the less severe of the two syndromes.

Disease Database

SPRED1 gene variant database

References

Phakomatosis (Q85, 759.5–759.6)

Neurofibromatosis	Type I Type II

Angiomatosis	Sturge–Weber syndrome Von Hippel–Lindau disease

Hamartoma	Tuberous sclerosis Hypothalamic hamartoma (Pallister–Hall syndrome) Multiple hamartoma syndrome Proteus syndrome Cowden syndrome Bannayan–Riley–Ruvalcaba syndrome Lhermitte–Duclos disease

Other	Abdallat–Davis–Farrage syndrome Ataxia telangiectasia Incontinentia pigmenti Peutz–Jeghers syndrome

Deficiencies of intracellular signaling peptides and proteins

GTP-binding protein regulators

GTPase-activating protein	Neurofibromatosis type I Watson syndrome Tuberous sclerosis

Guanine nucleotide exchange factor	Marinesco–Sjögren syndrome Aarskog–Scott syndrome Juvenile primary lateral sclerosis X-Linked mental retardation 1

G protein

Heterotrimeic	cAMP/GNAS1: Pseudopseudohypoparathyroidism Progressive osseous heteroplasia Pseudohypoparathyroidism Albright's hereditary osteodystrophy McCune–Albright syndrome CGL 2

Monomeric	RAS: HRAS Costello syndrome KRAS Noonan syndrome 3 KRAS Cardiofaciocutaneous syndrome RAB: RAB7 Charcot–Marie–Tooth disease RAB23 Carpenter syndrome RAB27 Griscelli syndrome type 2 RHO: RAC2 Neutrophil immunodeficiency syndrome ARF: SAR1B Chylomicron retention disease ARL13B Joubert syndrome 8 ARL6 Bardet–Biedl syndrome 3

MAP kinase

Cardiofaciocutaneous syndrome

Other kinase/phosphatase

Tyrosine kinase	BTK X-linked agammaglobulinemia ZAP70 ZAP70 deficiency

Serine/threonine kinase	RPS6KA3 Coffin-Lowry syndrome CHEK2 Li-Fraumeni syndrome 2 IKBKG Incontinentia pigmenti STK11 Peutz–Jeghers syndrome DMPK Myotonic dystrophy 1 ATR Seckel syndrome 1 GRK1 Oguchi disease 2 WNK4/WNK1 Pseudohypoaldosteronism 2

Tyrosine phosphatase	PTEN Bannayan–Riley–Ruvalcaba syndrome Lhermitte–Duclos disease Cowden syndrome Proteus-like syndrome MTM1 X-linked myotubular myopathy PTPN11 Noonan syndrome 1 LEOPARD syndrome Metachondromatosis

Signal transducing adaptor proteins

Other

NF2
- Neurofibromatosis type II
NOTCH3
- CADASIL
PRKAR1A
- Carney complex
PRKAG2
- Wolff–Parkinson–White syndrome
PRKCSH
- PRKCSH Polycystic liver disease
XIAP
- XIAP2

See also intracellular signaling peptides and proteins

Index of cells

Description	Structure nucleus chromosome genetics Organelles peroxisome cytoskeleton centrosome epithelia cilia mitochondria Membranes proteins cell adhesions Membrane transport ion channels vesicular transport solute carrier ABC transporters ATPase oxidoreduction-driven

Disease	Structural peroxisome cytoskeleton cilia mitochondria nucleus scleroprotein Membrane channelopathy solute carrier ATPase ABC transporters other extracellular ligands cell surface receptors intracellular signalling Vesicular transport Pore-forming toxins