Rasopathies (overview)

The term "RASopathies ", also"Neuro-Cardio-Facio-Cutaneous Syndromes", is used to describe a clinically and genetically heterogeneous group of diseases that are caused by gene mutations (germline mutations) in genes that code for proteins of the RAS/MAPK(mitogen-activated protein kinase) signalling pathway.

RASopathies are characterizedby symptoms in multiple organ systems. These include:

• the skin organ
• the cardiovascular system
• the skeletal system
• Musculature
• gastrointestinal tract
• central nervous system and
• eyes.

The following diseases are classified as RASopathies:

• Neurofibromatosis type I (NF1 gene).
• Legius syndrome (SPRED1 gene), a syndrome similar to neurofibromatosis type I with a different mutation (see above)
• Lelis syndrome(palmo-plantar hyperkeratoses, acanthosis nigricans, nail dystrophies, mental retardation)
• Naxos syndrome (mutation of the JUP gene, which codes for phacoglobin, an integral component of desmosomes) palmo-plantar hyperkeratoses, frizz hair, right cardiac cardiomyopathy)
• Carvajal syndrome (mutation of the DSP gene, which also encodes phacoglobin) palmo-plantar hyperkeratosis, frizzy hair, left cardiac cardiomyopathy occurring in early childhood)
• Rothmund-Thomson syndrome
• Costello syndrome (among others, a heterozygous missense mutation c.34G>A (p.Gly12Ser) in exon 2 has been detected; mutations in sections of the HRAS gene are rarer )
• Cardiofasciocutaneous syndrome(Noonan-related syndromes: short stature, mental retardation, facial dysmorphia, cardiac anomalies, hyperextensible joints, cutis laxa, hyperkeratoses, hyperhidrosis, curly hair that is usually easily epilated(loose anagen hair syndrome), acanthosis nigricans, nail dystrophies)
• CFC syndrome (cardio-facio-cutaneous syndrome)

For clarification, a step-by-step diagnosis using next generation sequencing (NGS) should be performed.

1. Costello JM (1971) A new sydrnome. NZ Med J 74:397
2. Wirtz M et al (2015) Costello syndrome, a rare RASopathy with cutaneous symptoms, dermatologist 66:225-228