Neurocutaneous Disease

Classification according to ICD-10
Q85.-	Phacomatoses, not elsewhere classified
ICD-10 online (WHO version 2019)

The neurocutaneous disease ( synonym : phacomatoses , neuroectodermal diseases ) are characterized by manifestations of the two institutions skin and nervous system . The classification of this group of diseases varies depending on the textbook author.

Variants of classification

The textbook of neurology by Mumenthaler (1979) defines phakomatoses as malformations of the central nervous system and skin and includes neurofibromatosis Recklinghausen (NF), tuberous sclerosis Bourneville-Pringle (TS), encephalo-facial angiomatosis Sturge-Weber (EFA) and retino-cerebellar angiomatosis Hippel-Lindau (RZA).

The textbook of neurology by Delank (1994) defines neurocutaneous diseases on the basis of histological and embryological considerations. There it is said that the phakomatoses are dysplastic-blastomatous developmental disorders that affect ectodermal structures and thus occur as neurocutaneous diseases. The ectodermal dysplasias would become tumors and hemangiomatous malformations were of mesenchymal origin and thus formed secondarily from ectodermal tissue. Delank also counts NF, TS, EFA and RZA among the phacomatoses.

In Merrit's Textbook of Neurology (1996) in the chapter Neurocutaneous Disorders only the neurofibromatosis Recklinghausen (congenital tumor disease), the Encephalofaciale- / trigeminal angiomatosis Sturge-Weber (crab / Dimitri) (a congenital vascular malformation), which Incontinentia Pigmenti Bloch Sulzberger (a congenital eruptive skin disease) and Bourneville-Pringle tuberous sclerosis (again a congenital tumor). The chapter author Arnold P. Gold does not give a more detailed reason for the selection of the diseases.

The authors VF Mautner and SM Pulst discuss neurofibromatosis type 1 and type 2, tuberous sclerosis and von Hippel-Lindau syndrome in the chapter on phakomatoses in the textbook on neurogenetics by Rieß and Schöls (1998) with the note that phakomatoses act By definition, they are diseases of the skin and retina and the diseases mentioned are genetically characterized by the loss of function of tumor suppressor genes .

Reim's textbook on ophthalmology classifies phakomatoses among the hereditary tumors of the retina and mentions, in addition to retinoblastoma, the so-called mulberry tumors of Bourneville's tuberous sclerosis and angiomatosis retinae of retino-cerebellar angiomatosis Hippel-Lindau. The encephalo-facial angiomatosis Sturge Weber is mentioned because of its hemangiomas of the ciliary body and the neurofibromatosis Recklinghausen because of its iris nevi ( Lisch nodules ), which are pathologically characterized as melanocytic hamartomas .

In contrast, the textbook by Fitzgerald Dermatology in General Medicine (1987) gives a generous definition, so that numerous disorders are listed there under the heading of neurocutaneous diseases .

First, a classification is proposed that is as little restrictive as possible. The causes of the problems cataloging the disorder are discussed later in this article.

Main classifications

Pragmatically, neurocutaneous diseases should be divided into four groups:

1. Congenital diseases and developmental disorders
2. Diseases that affect the skin and nervous system ( phenylketonuria , homocystinuria )
3. Nervous diseases with skin symptoms ( herpes zoster , syringomyelia )
4. Skin diseases with neurological symptoms ( melanoma , tetanus , rabies )

Subgroups of neurocutaneous diseases

The first subgroup is the largest and is again subdivided several times:

Among the congenital, benign tumors are in neurocutaneous diseases:

• the neurofibromatosis type I Recklinghausen :
• the Tuberous Sclerosis Tuberous Sclerosis .
• the retinal and cerebellar hemangioblastosis Hippel-Lindau .

The congenital vascular malformations in neurocutaneous diseases include:

• the angiomatosis of the face (craniofacial or trigeminocranial) Sturge-Weber-Dimitri .
• the retinal and cerebellar hemangioblastosis Hippel-Lindau .
• the Osler Osler-Weber-Rendu .
• the Ataxia teleangiectatica Louis Bar .

The congenital eruptive diseases of the skin with involvement of the nervous system include:

• the Incontinentia Pigmenti Bloch-Sulzberger
• the epidermolysis bullosa

Among the congenital pigmentation count with unusual development of the nervous system:

• the Waardenburg syndrome
• the syndrome of the giant pigmented nevus with involvement of meninges and malignant melanoma.

The congenital ichthyoses, xerodermias and hyperkeratoses with involvement of the nervous system include:

• the foliage ovary syndrome ( xeroderma and ataxia)
• the Stewart syndrome (ichthyosis, retinitis, muscle atrophy)
• the Sjögren-Larsson syndrome (ichthyosis and spastic paraplegia)
• the Refsum syndrome (hypertrophic polyneuropathy, Retinitis pigmentosa , cerebellaäre ataxia )

One of the most common developmental neurocutaneous disorders is one

• the spina bifida

The congenital somatic disorders with chromosomal peculiarities and changes in the skin and nervous system include:

• Turner Syndrome
• Down syndrom
• Klinefelter Syndrome

history

The name of the synonym phakomatosis is derived from the Greek word phakos (lens spot ). It was introduced by I. van der Hoeve to describe retinal lesions in patients with tuberous sclerosis.

Principles of classification

Following the considerations of Raymond Adams in Fitzgerald et al., Four different groups of neurocutaneous diseases can in principle be distinguished. The first group classifies the diseases according to histological and pathogenetic relationships. The second is based on a common damage mechanism (deficiency states or metabolic disorders that damage both organ systems at the same time: pellagra , cretinism ). The third describes diseases in which there is a primary disorder of the nervous system and has secondary consequences on the skin (trophic disorders of the skin in PNP) and the fourth describes in return diseases in which there is a primary disorder of the skin, the secondary consequential damage nervous system (combined a viral rash , one encephalitis caused).

Pathogenetic Mechanisms

Six different pathogenetic mechanisms can be distinguished:

• Disturbances in the course of embryonic development that affect the cells of the neural crest .
• Disorders of the relationship between Schwann cells and endoneurial fibroblasts.
• Melanocyte disorders
• Developmental disorders of vessels in the skin and nervous system.
• Disorders of the relationship between adipocytes and nerve cells.
• Metabolic diseases that affect skin cells and nerve cells.

The group of neurofibromatoses

There are four different subtypes of neurofibromatosis:

• peripheral neurofibromatosis type I (hyperpigmentation and neurofibromas).
• central neurofibromatosis type II (bilateral acoustic neuromas at the age of 20).
• the segmental form of segmental neurofibromatosis (clinically like NF type I, but limited to one body segment).
• the purely cutaneous form of cutaneous neurofibromatosis with skin tumors without any further clinical manifestations.

Type I neurofibromatosis was the first hereditary tumor disease whose molecular mechanism was elucidated. The gene could only be cloned after the patient populations had been homogenized using the diagnostic criterion of Lisch nodules. Lisch nodules are only found in NF type I. These facts influence the clinical picture and the course of the disease.

See also

List of syndromes

Sources and literature

• Adams: Neurocutaneous Diseases. In: Fitzgerald et al.: Dermatology in General Medicine. 1987.
• Lewis P. Rowland: Merrits Textbook of Neurology . Williams and Wilkins, Baltimore 1995, ISBN 0-683-07400-8 .
• Olaf Rieß and Ludger Schöls (eds.) Neurogenetics. Molecular genetic diagnosis of neurological diseases. Springer Verlag, Berlin 1998, ISBN 3-540-63874-1 .
• I. van der Hoeve: Eye symptoms of tuberous sclerosis of the brain. In: Trans. Ophthalmol. Soc. UK. 1920; 40, p. 329.
• FW Crowe et al: A Clinical, Pathological and Genetic Study of Multiple Neurofibromatoses. Charles C. Thomas, Springfield 1956.
• VM Riccardi: Neurofibromatosis: Phenotype, Natural History and Pathogenesis. Johns Hopkins University Press. Baltimore 1992.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !