Neurocutaneous

Neurocutaneous markers and syndromes

1. NEUROCUTANEOUS SYNDROME Guide- Dr.Karan Joshi

2. References:- Nelson-Textbook of Pediatrics 19 th Edition Rudolph-textbook of Pediatrics 21 st Edition Illustrated synopsis of Dermatology and sexually transmitted diseases- 3 rd Edition…. Neena Khanna Medscape.com

3. OUTLINE- Introduction Various Syndromes Epidemiology Etiology Clinical Features Diagnosis Treatment

4. INTRODUCTION Heterogenous group of disorders characterised by the abnormalities of integument and CNS. Mostly familial. Defect in differentiation in primitive ectoderm .

5. The various syndromes include- Neurofibromatosis Tuberous Sclerosis Sturge Weber Syndrome Von Hippel Lindau Syndrome PHACE Syndrome Linear nevus Syndrome Incontinentia Pigmenti

6. NEUROFIBROMATOSIS

7. INTRODUCTION- NF1 and NF2 are autosomal dominant. 50% of cases having no family history. NF1 is also called Von Recklinghausen disease. NF2 is also called bilateral acoustic neurofibromatosis ETIOLOGY NF1 is caused by DNA mutations located on the long arm of chromosome 17 NF2 is caused by DNA mutations located in the middle of the long arm of chromosome 22

8. EPIDEMIOLOGY AND DEMOGRAPHICS NF 1 is the most common neurocutaneous syndrome, affecting approximately 1/3000 persons. NF 2 occurs in about 1/50,000 Equally affects males and females.

9. COMMON FEATURES & PRESENTATION CAFE-AU-LAIT SPOTS Discrete, well-circumscribed uniformly brown lesions with irregular border 5mm( prepubertal ) 15mm( postpubertal )

10. AXILLARY FRECKELS Small (0.5cm) brown, well-circumscribed macules . Generally go unnoticed. High correlation with neurofibromatosis when six or more freckles are present in the axilla .

11. LISCH NODULES A pigmented hamartomatous nevus (a type of benign tumor ) affecting the iris.

12. Neurofibroma and plexiform neurofibroma

13. Common features of NF2 include : Hearing loss and tinnitus Cataracts Headache Unsteady gait Cutaneous neurofibromas Café-au- lait macules (1%)

14. DIAGNOSTIC CRITERIA NF1 is diagnosed if any 2 of the following 7 are present:- Six or more café-au- lait macules >5 mm in prepubertal patients and >15 mm in postpubertal patients Two or more neurofibromas of any type or one plexiform neurofibroma Axillary or inguinal freckling Optic glioma Two or more Lisch nodules Sphenoid wing dysplasia or cortical thinning of long bones, with or without pseudarthrosis A first-degree relative (parent, sibling, or child) with NF1 based on the previous criteria

15. NF 2 diagnosed when any of the following 4 features is present:- Bilateral eighth nerve masses seen by appropriate imaging studies- Bilateral vestibular schwannomas OR A unilateral eighth nerve mass A first-degree relative with NF2 OR two of the following: Neurofibroma , meningioma, glioma , schwannoma or juvenile posterior subcapsular lenticular opacity

16. WORKUP AND TREATMENT Genetic counselling Molecular testing MRI MANAGEMENT- Supportive &Symptomatic Neurologic and educational testing Close & disciplinary follow up Surgical All symptomatic cases( visual disturbance,proptosis , raised ICT) should be assesed without any delay

17. TUBEROUS SCLEROSIS (Bourneville’s disease,Epiloia )

18. INTRODUCTION The classic clinical Triad is Skin lesions in association with Epilepsy and Mental retardation . Multisystemic disorder. ETIOLOGY AND EPIDEMIOLOGY Autosomal dominant disorder Frequency 1/6,000 Mutations occur on chromosome 9q34 (TSC1) and 16p13.3 (TSC2). TSC1 gene encode hamartin and TSC2 encodes tuberin Half of cases are due to new mutations.

19. PATHOLOGY Tubers( cerebrum,SER ) Calcification & project into ventrical cavity ( candle dripping appearance) If present in the foramen of monero Obstruction of CSF(hydrocephalus)

20. Clinical Manifestations A sh-leaf Macule (Reliable early cutaneous sign ) Shagreen Patch

21. Cafe-au- lait spots Adenoma sebaceous

22. Subungual fibroma Periungual fibroma

23. Two astrocytomas (one is calcified ) Renal Angiomyolipoma

24. The frequency of signs in children with tuberous sclerosis, grouped by age  

25. C ortical tuber Subependymal nodule Subependymal giant cell astrocytoma Facial angiofibroma or forehead plaque Ungual or periungual fibroma Hypomelanotic macules (>3) Shagreen patch Multiple retinal hamartomas Cardiac rhabdomyoma Renal angiomyolipoma Pulmonary lymphangiomyomatosis MAJOR FEATURES OF TUBEROUS SCLEROSIS COMPLEX

26. Cerebral white matter migration lines Multiple dental pits Gingival fibromas Bone cysts Retinal achromatic patch Confetti skin lesions Nonrenal hamartomas Multiple Renal cysts Hamartomatous rectal polyps MINOR FEATURES OF TUBEROUS SCLEROSIS COMPLEX TSC is diagnosed when at least 2 major or 1 major plus 2minor features present

27. Diagnosis:- Diagnosis of TS relies on a high index of suspicion when assessing a child with infantile spasms. A careful search for the typical skin and retinal lesions should be completed in all patients with a seizure disorder. Head CT scan or MRI confirms the diagnosis in most cases. The CT scan typically shows calcified tubers in the periventricular area. Molecular testing.

28. Ventriculomegaly and multiple calcified subependymal nodules in the lateral ventricles Periventricular Tubers

29. MANAGEMENT:- Control seizures Infantile spasms associated with TSC, should be given viagabatrin . Prognosis: 75% of patients with tuberous sclerosis die before the age of 25 yr, most commonly as a complication of: Epilepsy Intercurrent infection Cardiac failure Pulmonary fibrosis

30. STURGE WEBER SYNDROME

31. INTRODUCTION- Occurs sporadically, with a frequency of approximately 1/50,000 and consists of: Facial capillary malformation (port-wine stain) Leptomeningeal angioma Patient presents with- Seizures Hemiparesis Transient Stroke Headache Developmental delay

32. Clinical manifestations The facial nevus is present at birth,mostly unilateral and always involves the upper face and eyelid . Unilateral in 70% and ipsilateral to the venous angioma of the pia Even when the facial nevus is bilateral,the pial angioma is usually unilateral Buphthalmos and glaucoma of the ipsilateral eye are a common complication Seizures Hemiparesis Mental retardation and learning disabilities(50%)

33. Diagnosis X-Ray skull- calcification in occipitoparietal region (mostly) with serpentine or rail track appearance CT head - unilateral cortical atrophy and ipsilateral dilatation of the lateral ventricle

34. Ophthalmologic evaluation( ROACH SCALE) Type I: Both facial and leptomeningeal angiomas , may have glaucoma Type II: Facial Angioma alone,may have glaucoma Type III: Isolated leptomeningeal angiomas , no glaucoma

35. Management Treat seizure Hemispherectomy or lobectomy Regular measurements of intraocular pressure with a tenonometer is indicated. Flashlamp -pulsed laser therapy Special educational facilities

36. VON HIPPEL LINDAU DISEASE Autosomal dominant Affects many organs include cerebellum, spinal cord, medulla, retina, kidney, pancreas, and epididymis . Gene mapped in VHL is chromosome 3p25. The major neurologic features include Cerebellar hemangioblastomas Retinal angiomas

37. Patients with cerebellar hemangioblastoma (25%)have retinal angiomas Vision is unaffected Retinal detachment and visual loss. MANAGEMENT Retinal angiomas should be treated with photocoagulation and cryocoagulation Regular follow-up and appropriate imaging studies Renal carcinoma is the most common cause of death

38. INCONTINENTIA PIGMENTI (Bloch-Sulzberger syndrome)

39. INTRODUCTION X-linked, dominantly inherited disorder of skin pigmentation associated with CNS, ocular, and dental abnormalities. Female carriers may have features of stage IV and dental abnormalities Lethal in the majority of affected males Nuclear factor kappa B essential modulator (NEMO) is located at Xq28.

40. Stage 1 : ( VESICULAR) At birth Linear vesicles, pustules, and bullae with erythema along the lines of Blaschko . Stage 2: (VERRUCOUS) Between ages 2 and 8 weeks Warty, keratotic papules and plaques. Stage 3 : (HYPERPIGMENTED) Between ages 12 and 40 weeks. Macular hyperpigmentation in a swirled pattern along the lines of Blaschko . Also involve the nipples, axilla , and groin. Stage 4: (HYPOPIGMENTED) From infancy through adulthood. Hypopigmented streaks and/or patches and cutaneous atrophy.

41. CLINICAL FEATURES Skin lesions Dental anomalies(80%) Late dentition Hypodontia Conical teeth CNS Motor and cognitive developmental retardation Seizures Microcephaly Spasticity Paralysis(one third). Ocular anomalies Neovascularization , Microphthalmos Strabismus, Optic nerve atrophy Cataracts Rretrolenticular masses(30%)

42. WORKUP AND MANAGEMENT CBC CT scan & MRI Molecular genetics Skin biopsy There is no specific treatment for incontinentia pigmenti . Stage 1 lesion left intact & keep clean Dental care CONSULTATION Ophthalmologist Dentist Neurologist

43. PHACE SNDROME Cutaneous condition characterised by multiple congenital abnormalities. Posterior fossa malformations– hemangiomas –arterial anomalies–cardiac defects–eye abnormalities– sternal cleft and supraumbilical raphe syndrome Female Predominance Unknown underlying pathology Large plaque-type facial hemangiomas May be associated with Dandy Walker Malformations Cerebrovascular & cardiovascular anomalies are common

44. LINEAR NEVUS SYNDROME Characterized by a facial nevus and neurodevelopmental abnormalities. Nevus is located on the forehead and nose Midline in its distribution. PATHLOGY- Facial nevus includes 3 stages- 1 st - Infancy Alopecia Hypoplastic sebaceous glands 2 nd -Puberty Hyperplastic sebaceous glands 3 rd -Later in life Tumors(15-20%)

45. CLINICAL FEATURES- Skin Facial nevus CNS Seizures Hemiparesis Mental retardation Occular Esotropia Coloboma (iris &choroid) Homonymous hemianopia Others COA,VSD,Wilms tumor,nephroblastoma,scoliosis , bony hypertrophy

46. WORKUP AND MANAGEMENT CT scan & MRI EEG No specific treatment Treat seizures Multidisciplinary approach

47. THANKS Dr.Yashomati Parte