Neurocutaneous Disorders (eBook)

Dr. Martino Ruggieri, Institute of Neurological Science (ISN), National Research Council (CNR), Catania Prof. Dr. Ignacio Pascual-Castroviejo, Professor of Paediatric Neurology, Madrid Prof. Dr. Concezio Di Rocco, Instituto di Neurochirurgica, Univ. Cattolica del Sacro Cuore, Roma (Editor-in-Chief "Child's Nervous System")

Foreword 7
PREFACE 9
Contents 11
EMBRYOLOGY OF NEUROCUTANEOUS SYNDROMES 22
VASCULAR BIRTHMARKS OF INFANCY: PHACE ASSOCIATION ( PASCUAL- CASTROVIEJO TYPE II SYNDROME) AND COBB SYNDROME 39
NEUROFIBROMATOSIS TYPE 1 & RELATED DISORDERS
NEUROFIBROMATOSIS TYPE 2 AND RELATED DISORDERS 171
THE TUBEROUS SCLEROSIS COMPLEX 199
VON HIPPEL- LINDAU DISEASE 246
KLIPPEL–TRANAUNAY, PARKES WEBER AND STURGE– WEBER SYNDROMES ( INCLUDING KASABACH– MERRIT PHENOMENA) 266
KLIPPEL–TRENAUNAY SYNDROME 273
PARKES WEBER SYNDROME 292
STURGE- WEBER SYNDROME 301
OSLER- WEBER- RENDU SYNDROME ( HEREDITARY HEMORRHAGIC TELANGIECTASIA) 324
MACROCEPHALY- CUTIS MARMORATA TELANGIECTATICA CONGENITA ( MACROCEPHALY- CAPILLARY MALFORMATION) 335
BLUE RUBBER BLEB NEVUS SYNDROME ( BRBNS) 345
WYBURN- MASON SYNDROME 357
MAFFUCCI SYNDROME 365
HYPOMELANOSIS OF ITO AND RELATED DISORDERS ( PIGMENTARY MOSAICISM) 375
PHYLLOID HYPOMELANOSIS 398
INCONTINENTIA PIGMENTI 403
SILVER HAIR SYNDROMES: CHEDIAK- HIGASHI SYNDROME ( CHS) AND GRISCELLI SYNDROMES ( GS) 419
CHEDIAK- HIGASHI SYNDROME ( CHS) 422
GRISCELLI SYNDROMES ( GS) 430
LEOPARD SYNDROME 439
NEVUS OF OTA 447
PHACOMATOSIS PIGMENTOKERATOTICA 452
PHAKOMATOSIS PIGMENTOVASCULARIS 459
SPECKLED LENTIGINOUS NEVUS SYNDROME 465
CUTIS TRICOLOR ( RUGGIERI– HAPPLE SYNDROME) 470
NEUROCUTANEOUS MELANOSIS 481
GENETICS OF PTEN HAMARTOMA TUMOR SYNDROME ( PHTS) 490
LHERMITTE– DUCLOS AND COWDEN DISEASE COMPLEX 497
BANNAYAN- RILEY- RUVALCABA SYNDROME 516
ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS ( HABERLAND SYNDROME) 521
PROTEUS SYNDROME 530
EPIDERMAL NEVUS SYNDROMES 550
SCHIMMELPENNING- FEUERSTEIN- MIMS SYNDROME ( NEVUS SEBACEOUS SYNDROME) 561
INFLAMMATORY LINEAR VERRUCOUS EPIDERMAL NEVUS ( ILVEN) 576
NEVUS COMEDONICUS SYNDROME 582
BECKER’S NEVUS SYNDROME ( PIGMENTARY HAIRY EPIDERMAL NEVUS) 589
CHILD SYNDROME 595
CHONDRODYSPLASIA PUNCTATA ( CDP) CONRADI- HUNERMANN- HAPPLE TYPE ( CDPX2) 602
CONRADI– HUNERMANN– HAPPLE SYNDROME 605
SJÖGREN– LARSSON SYNDROME 613
KID SYNDROME ( KERATITIS- ICHTHYOSIS- DEAFNESS) 623
PAPILLON– LEFÈVRE SYNDROME ( PLS) 631
RICHNER– HANHART SYNDROME ( TYROSINE TRANSAMINASE DEFICIENCY) 641
DARIER’S DISEASE 646
DYSKERATOSIS CONGENITA 657
NEVOID BASAL CELL CARCINOMA ( GORLIN) SYNDROME 665
MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B 691
TURCOT SYNDROME 698
DEGOS’ DISEASE ( MALIGNANT ATROPHIC PAPULOSIS) 719
ATAXIA-TELANGIECTASIA 725
NIJMEGEN BREAKAGE SYNDROME 753
XERODERMA PIGMENTOSUM 764
COCKAYNE SYNDROME 786
TRICHOTHIODYSTROPHY 813
PROGERIA AND PROGEROID SYNDROMES ( PREMATURE AGEING DISORDERS) 838
FOCAL DERMAL HYPOPLASIA SYNDROME ( GOLTZ SYNDROME) 870
EHLERS– DANLOS SYNDROMES 878
LIPOID PROTEINOSIS 898
PROGRESSIVE FACIAL HEMIATROPHY ( PARRY- ROMBERG SYNDROME) 906
LINEAR SCLERODERMA ( MORPHOEA) “ EN COUP DE SABRE” 911
UNILATERAL SOMATIC AND INTRACRANIAL HYPOPLASIA 917
OCULOCEREBROCUTANEOUS SYNDROME ( DELLEMAN SYNDROME) 920
CEREBELLO-TRIGEMINAL DERMAL DYSPLASIA ( GOMEZ- LOPEZ- HERNANDEZ SYNDROME) 924
MACRODACTYLY- LIPOFIBROMATOUS HAMARTOMA OF NERVES 930
CHIME SYNDROME ( ZUNICH SYNDROME) 937
HYPOHIDROTIC ECTODERMAL DYSPLASIA ( HED) 944
COSTELLO SYNDROME AND THE RAS- EXTRACELLULAR SIGNAL REGULATED KINASE ( ERK) PATHWAY 953
ANDERSON- FABRY DISEASE 973
CEREBROTENDINOUS XANTHOMATOSIS 984
GIANT AXONAL NEUROPATHY 995
LESCH– NYHAN SYNDROME 1000
THE SKIN AS A CLUE FOR THE DIAGNOSIS OF INHERITED METABOLIC DISORDERS 1006
SKIN INVOLVEMENT AS A CLINICAL MARKER OF NEUROMUSCULAR DISORDERS 1026
SUBJECT INDEX 1039

GENETICS OF PTEN HAMARTOMA TUMOR SYNDROME (PHTS) (p. 483)

Corrado Romano

Unit of Paediatrics and Medical Genetics, IRCCS OASI Maria Santissima, Troina, Italy

Introduction

PTEN hamartoma tumor syndrome (PHTS) (Marsh et al. 1999) can be defined as a syndromic condition including one or more hamartomas which has its biological basis in a germline mutation of the Phosphatase and Tensin Homolog deleted on Chromosome 10 (PTEN) gene. Following such assumption, PHTS includes patients with the previous diagnosis of Cowden syndrome (CS) (Weary et al. 1972), Bannayan-Riley-Ruvalcaba syndrome (BRRS) (Cohen 1990), Proteus syndrome (PS) (Wiedemann et al. 1983), Proteus-like syndrome (PLS) (Zhou et al. 2000) and Lhermitte–Duclos syndrome (LDS) (Dastur et al. 1975). Conversely, those conditions not including hamartomas within their phenotype but presenting with a PTEN mutation (Butler et al. 2005) cannot be considered as part of the PHTS spectrum. Currently, failure to detect a PTEN mutation doesn’t imply the ruling out of a clinical diagnosis of CS, BRRS, PS, PLS or LDS in patients who fulfill the clinical diagnostic criteria for these conditions, however, the term PHTS should be avoided in this case.

The PHTS

CS, BRRS, PS, PLS and LDS are extensively addressed in other chapters of this book. The aim of this paragraph is to make the reader aware of how the discovery of PTEN gene has changed the understanding of the above mentioned conditions and has prompted the need of using the new definition of PHTS. The International Cowden Consortium proposed in 1995 a set of operational criteria for the diagnosis of CS cases and families aimed at the search for the CS gene (Nelen et al. 1996, Liaw et al. 1997). The importance and robustness of these criteria are highlighted by the PTEN mutation rate, which is 80% (Liaw et al. 1997, Marsh et al. 1998b), when they are administered strictly, whereas is 10–50% (Tsou et al. 1997, Lynch et al. 1997,Nelen et al. 1997), when they are not used. A study has been performed in 1998 on CS-like families (Marsh et al. 1998a), in order to increase the knowledge about the PTEN mutation clinical spectrum. One of the 64 CS-like cases was found to have a germline PTEN mutation. Bilateral breast cancer, follicular thyroid carcinoma, and endometrial adenocarcinoma were running in that family. Five out of 103 (5%) women with multiple primary cancers were found to have PTEN germline missense mutations, with proven resulting loss of function (De Vivo et al. 2000). Two of these five cases had endometrial cancer. Consequently, PTEN germline mutations can be found in hamartomatous conditions not fulfilling the diagnostic criteria of CS, and endometrial carcinoma might be an important part of CS, increasing the probability of finding a PTEN mutation in CS-like cases. The International Cowden Consortium has included, in the version released during year 2000, endometrial carcinoma in the operational criteria for the diagnosis of CS.