Neurocutaneous syndrome

1. NEUROCUTANEOUS
SYNDROME
DR. SUMIT KAMBLE
DM SENIOR RESIDENT
GMC, KOTA

2. INTRODUCTION
 Heterogeneous group of disorders characterised by the
abnormalities of integument and CNS.
 Mostly familial.
 Defect in differentiation in primitive ectoderm (nervous system,
eyeball, retina, and skin) .

3. Various syndromes include-
• Neurofibromatosis
• Tuberous Sclerosis
• Sturge Weber Syndrome
• Von Hippel Lindau Syndrome
• Ataxia-telangiectasia
• Hereditary Haemorrhagic Telangiectesia
• Epidermal nevus Syndrome

4. OTHERS
AD
• Hemorrhagic telangiectasia (Osler-Rendu-Weber)
• Incontinentia Pigmenti Achromians (Hypomelanosis of Ito)
AR
• Chediak-Higashi
• Divry-Van Boegart
• Meckel-Gruber
• Xeroderma pigmentosa
X-linked
• Albright syndrome (polyostotic fibrous dysplasia)
• Dyskeratosis congenita (Zinsser-Cole-Engman syndrome)
• Incontinentia Pigmenti (Bloch-Sulzberger)
No inheritance
• Cobb syndrome (cutaneous meningeal angiomatosis)
• Linear Sebaceous Naevus of Jadassohn

5. NEUROCUTANEOUS DISORDERS INCIDENCE
• Neurofibromatosis Type 1 1/1,000 -1/7,800
• Tuberous Sclerosis 10.6/100,000
• Ataxia Telangiectasia 1.7/100,000
• Xeroderma Pigmentosum 1/100,000 - 1/250,000
• Neurofibromatosis type 2 1/200,000

6. NEUROFIBROMATOSIS
• NF comprises two distinct disorders, genes for which are
located on different chromosomes.
• 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
• Cellular elements derived from the neural crest (i.e., Schwann
cells, melanocytes, and endoneurial fibroblasts, the natural
components of skin and nerves) proliferate excessively in
multiple foci.

7. NEUROFIBROMATOSISTYPE 1 (CLASSICALOR
PERIPHERALNF)
• Most prevalent type
• Incidence of 1/3,000
• Autosomal dominant disorder
• Over half the cases are sporadic, representing De novo
mutations.
• Chromosome region 17q11.2
• Encodes a protein also known as Neurofibromin.

8. DIAGNOSTIC CRITERIAOFNF TYPE 1
Diagnosed when any 2 or more of the following 7 features are
present:
• (1) Six or more Cafe-au-lait macules (macules >5 mm in prepubertal patients
and >15 mm in postpubertal patients )
• (2) Axillary or inguinal freckling .
• (3) Two or more iris Lisch nodules
• (4) Two or more neurofibromas or 1 plexiform neurofibroma
• (5) A distinctive osseous lesion such as Sphenoid dysplasia , thinning long
bone cortex + pseudarthrosis.
• (6) Optic gliomas low-grade astrocytomas.
• (7) A first-degree relative with NF- 1

9. Cafe-au-lait macules
• Hallmark of neurofibromatosis
almost 100% of patients.
• Present at birth but increase in
size, number, and pigmentation,
especially during first few years
of life.
• Predilection for the trunk and
extremities but sparing the face.

10. Axillary or inguinal freckling
• Multiple hyperpigmented areas
2-3 mm in diameter.
• Skinfold freckling usually
appears between 3 and 5 years of
age.
• Frequency greater than 80% by 6
year of age.
• High correlation with
neurofibromatosis when six or
more freckles are present in the
axilla.( Crowe sign)

11. Two or more iris Lisch nodules
• Pigmented hamartomatous nevus
(type of benign tumor) affecting
iris.
• Best identified by a slit-lamp
examination.
• Present in >74%
• Prevalence increases with age.
Only 5% of children <3 yr of age.
42% among children 3-4 yr of age.
100% of adults ≥21 yr of age.

12. Two or more neurofibromas or 1
plexiform neurofibroma
• Neurofibroma- benign tumors arising
from Peripheral nerve.
• Small, rubbery lesions with a slight
purplish discoloration of overlying skin.
• Plexiform neurofibromas are usually
evident at birth and result from diffuse
thickening of nerve trunks that are
frequently located in the orbital or
temporal region of the face.
• Plexiform neurofibromas may produce
overgrowth of an extremity and a
deformity of the corresponding bone
• 5-13% risk of malignant transformation

13. Distinctive Osseous lesion
• Sphenoid Dysplasia
• Scoliosis is Most Common
• Cortical thining of long bones
with or without pseudoarthrosis

14. SYSTEMIC FEATURES OFNF1
• Dysplasia of renal and carotid arteries
• Systemic hypertension – Renal artery stenosis and
pheochromocytoma
• Cerebral artery dysplasia- Moyamoya syndrome
• Arterial aneurysms
• Short stature and Macrocephaly with normal-sized ventricles
• Precocious puberty may become evident in the presence or
absence of lesions of the optic chiasm and hypothalamus
• Pheochromocytoma, Rhabdomyosarcoma, Leukemia, and
Wilms tumor

15. NEUROLOGICALFEATURES OFNF1
Optic nerve Glioma
• Most common CNS tumor
• Seen 15% - Unilateral or
bilateral
• Progressive vision loss, optic
atrophy, pain or proptosis
• Precocious puberty- chiasmatic
optic nerve tumor
• Children age >10 years with
NF-1 undergo annual
ophthalmologic examinations

16. NEUROLOGICALFEATURES OFNF1
• Ependymomas, Meningiomas and Astrocytomas
• Neurofibromas, Schwannomas
• Other MRI Abnormalities
• Areas of increased T2 signal intensity (UBOs)
• – 43 - 79 % of NF1 in pediatric age group in BG, Thalamus, brainstem and
cerebellum
• – Most- multiple, no mass effect.
• – Path- atypical glial infiltrate, and areas of microcalcificaiton, and areas of
dysmyelination and spongy changes in WM around lesion

17. NEUROFIBROMATOSIS 2 (NF-2)
• Rarer condition
• Incidence of 1/25,000
• NF2 gene (also known as merlin or Schwannomin), located on
chromosome 22q1.11
• Posterior subcapsular lens opacities are identified In about 50%
of patients with NF-2
• Bilateral acoustic neuromas - most distinctive feature (In
contrast with NF-1 – optic gliomas).

18. DIAGNOSTIC CRITERIAOF NF TYPE 2
May be diagnosed when 1 of the following 3 Features is present:
1. Bilateral vestibular schwannomas
2. First degree relative with NF-2 and unilateral vestibular
schwannoma
3. First degree relative with NF-2 and any 2 of the following:
Meningioma, Schwannoma, Glioma, Neurofibroma, or
Posterior subcapsular lenticular opacities

19. Bilateral Acoustic Neuromas
• Hearing loss
• Unsteadiness
• Headache
• Facial weakness
• More commonly in 2nd and
3rd decade.
Subcapsular opacity- 50% of
cases of NF-2

20. LABORATORY TESTS
• Genetic testing is available. Results can only tell if an individual is
affected but cannot predict the severity of the disease.
IMAGING STUDIES
• MRI with gadolinium is the imaging study of choice in both NF1
and NF2 patients. MRI increases detection of optic gliomas, tumors
of the spine, acoustic neuromas, and “bright spots”

21. TREATMENT
• Primarily supportive
• AEDs for seizures
• Surgery for for accessible tumors
• Orthopedic procedures for bony deformities
• Routine MRI studies to screen for optic gliomas in non
symptomatic children

22. TUBEROUS SCLEROSIS (Bourneville’s disease)
• TSC is an extremely heterogeneous disease with a wide clinical
spectrum varying from severe mental retardation and
incapacitating seizures to normal intelligence and a lack of
seizures, often within the same family.
• Disease affects many organ systems other than skin and brain,
including heart, Kidney, eyes, lungs, and bone.

23. • Autosomal dominant trait with variable Expression.
• Prevalence of 1/6,000 newborns.
• Spontaneous genetic mutations occur in 2/3 of the Cases.
• Molecular genetic studies have identified 2 foci

24. • TSC1 and TSC2 genes are tumor suppressor Genes.
• Both are involved in a key pathway in the cell that Regulates
protein synthesis and cell size.
• Loss Of either tuberin or hamartin results in the Formation of
numerous benign tumors (Hamartomas)

25. DIAGNOSTIC CRITERIA
A. GENETIC DIAGNOSTIC CRITERIA
• Identification of Mutation in either TSC1 or TSC2
• 10% to 25% of TSC patients have no mutation ( normal result
does not exclude TSC)
B. CLINICAL DIAGNOSTIC CRITERIA
• Definite diagnosis: Two major features or one major feature
with ≥2 minor features
• Possible diagnosis: Either one major feature or ≥2 minor
features
•

26. Major features
1. Hypomelanotic macules (≥3, at least 5-mm diameter)
2. Angiofibromas (≥3) or fibrous cephalic plaque
3. Ungual fibromas (≥2)
4. Shagreen patch
5. Multiple retinal hamartomas
6. Cortical dysplasias
7. Subependymal nodules
8. Subependymal giant cell astrocytoma
9. Cardiac rhabdomyoma
10. Lymphangioleiomyomatosis (LAM)
11. Angiomyolipomas (≥2)

27. Minor features
1. “Confetti” skin lesions
2. Dental enamel pits (>3)
3. Intraoral fibromas (≥2)
4. Retinal achromic patch
5. Multiple renal cysts
6. Nonrenal hamartomas

28. DERMATOLOGICAND DENTALFEATURES
Hypomelanotic macules (Ash
leaf spots)
• Observed in about 90% of
individuals
• Typically appear at birth or infancy
Facial Angiofibromas
(adenoma sebaceum)
• About 75% of TSC patients
• Between ages 2 and 5 years
• Also seen in Birt-Hogg-Dubé
(BHD) syndrome, and (MEN1)

29. Ungual fibromas
• About 20% overall
• Adults
Shagreen patch
• Large plaques on the lower
back that have a bumpy or
orange-peel surface
• Seen in 50% of individuals
• Onset in the first decade

30. “ Confetti” skin lesions
• Numerous 1- to 3-mm
hypopigmented macules
scattered over arms and legs
• 3% in children to about 58%
overall
Dental enamel pits
• Multiple, randomly
distributed pits in dental
enamel
• 100% of adult TSC patients

31. Intraoral fibromas
• Occur in about 20–50% of individuals
• Gingival fibromas
• May also be observed on the buccal or labial mucosa and even the
tongue

32. OPHTHALMOLOGIC FEATURES
Multiple retinal hamartomas
• 30–50% of TSC
• Do not cause problems with
vision
Retinal achromic patch
• Areas of hypopigmentation
on the retina
• 39% of TSC patients

33. NEUROLOGICALFEATURES
• Intellectual disability, behavioral abnormalities
• Seizures - various types occur in 80% to 90% of patients.
• Most common cause of infantile spasms
• Neuropathological lesions of TSC include subependymal
nodules (SENs), cortical and subcortical hamartomas (tubers),
areas of focal cortical hypoplasia, and heterotopic gray matter.

34. Cortical tubers
Location- Frontal, Parietal,
Temporal,Cerebellar
Sub ependymal nodules
• Location-Caudothalamic
groove of lateral ventricle.

35. White matter lesions
• Location-alone lines of neural
migration
SEGA
• 6-14%

36. CARDIOVASCULAR FEATURES
Cardiac rhabdomyoma
• Major feature
• Benign tumors of heart that
are rarely observed in non-
TSC–affected individuals
• Most frequently located in the
ventricles
• Observed in TSC-affected
individuals during fetal life
• Prenatal presence of a cardiac
rhabdomyoma is associated
with a 75–80% risk of TSC

37. Pulmonary features
• Lymphangioleiomyomatosis
• Interstitial expansion of the
lung with benign-appearing
smooth muscle cells that
infiltrate all lung structures
• 30–40% of female TSC
patients
• Multifocal micronodular
pneumocyte hyperplasia
(MMPH)
• Clear cell tumor of the lung
Renal features
• Angiomyolipomas
• Benign tumors composed of
vascular, smooth muscle, and
adipose tissue
• 80% of TSC patients
• Multiple renal cysts

38. Endocrine features
• Hamartoma
• Adrenal angiomyolipoma
• Thyroid papillary adenoma
• Angiomyolipoma or
fibroadenoma in the pituitary
gland, pancreas, or gonads
Gastrointestinal features
• Liver angiomyolipomas
• Hamartomatous rectal polyps

39. STURGE WEBER SYNDROME
• Characteristic features are facial cutaneous angioma (port-wine
nevus) and an associated ipsilateral leptomeningeal and brain
angioma.
• Occurs sporadically, with a frequency of approximately
1/50,000
• Somatic mutation in GNAQ recently identified

40. CUTANEOUS FEATURES
Nevus (port-wine)
• Involves the forehead and
upper eyelid
• Usually obvious at birth;
• Reactive hypertrophy of
adjacent bone and connective
tissue
• Only 10% to 20% of children
with a port-wine nevus of the
forehead have leptomeningeal
angioma.
• Leptomeningeal angioma is
typically ipsilateral to a
unilateral facial nevus

41. OCULAR FEATURES
Glaucoma
• Risk has two age peaks, first in infancy and second in late
childhood.
• Periodic measurement of the intraocular pressure is mandatory,
particularly when the nevus is near the eye.
• Amblyopia and buphthalmos (enlarged globe)
• Choroid angiomas or heterochromasia of the iris ipsilateral to
the nevus.

42. NEUROLOGICALFEATURES
• Epileptic seizures- develop in 72% to 80% of patients with
unilateral lesions and in 93% of patients with bihemispheric
involvement.
• Focal motor seizures or generalized tonic-clonic seizures,
infantile spasms, myoclonic seizures, and atonic seizures
• Intellectual disability - Only 8% of the patients with bilateral
brain involvement are intellectually normal
• Focal neurological deficits- Transient stroke-like episodes or
visual defects

43. DIAGNOSTIC STUDIES
• Skull radiograph –Intracranial calcification in occipitoparietal
region.
• Gyral calcifications- characteristically assumes a serpentine or
railroad-track appearance.
• CT scan highlights the extent of the calcification that is usually
associated with unilateral cortical atrophy and ipsilateral
dilatation of the lateral ventricle.
• MRI is a useful adjunct to CT for delineation of the size and
location of the vascular malformation and the presence of white
matter lesions

44. Functional imaging
• PET- reduced metabolism of the brain adjacent to the
leptomeningeal lesion
• SPEC- reduced perfusion of the affected brain.
• Both PET and SPECT often reveal vascular changes extending
well beyond the area of abnormality depicted by CT
Cerebral arteriography –
• Useful in atypical patients or prior to surgery for epilepsy.
• Veins are more abnormal than the arteries, with enlarged,
tortuous, subependymal, and medullary veins and sparse
superficial cortical veins.

46. .
• Occipital gyriform
calcification pattern
• leptomeningeal and brain angioma

47. TREATMENT
• Treat seizure
• Resection of a localized brain vascular lesion or
hemispherectomy
• Because of the risk of glaucoma, regular measurements of
intraocular pressure with a tenonometer is indicated.
• Flashlamp-pulsed laser therapy holds considerable promise for
clearing of the port-wine stain.

48. VON-HIPPLE LINDAU DISEASE
• Autosomal dominant trait with variable penetrance and delayed
expression
• Incidence of 1/36,000 people
• Caused by germ line mutations in the VHL tumor suppressor
gene located on 3p25–26
• Affects many organs, including the cerebellum, spinal cord,
medulla, retina, kidney, pancreas, and epididymis

49. • Median age of presenting first clinical feature is 20-25 years.
• Earliest detected manifestation – capillary haemangioma of
retina.
• Probability of developing retinal capillary haemangioma and
CNS haemangioblastoma is 80%
• 60% probability for developing RCC
• Both sexes affected equally

50. NEUROLOGICALFEATURES
Hemangioblastomas - cerebellum in approximately half of
patients , followed by spinal and medullary sites.
• Begin in the second decade of life.
• Symptoms of cerebellar and brainstem hemangioblastomas-
headache, ataxia, nausea and vomiting, and nystagmus
• Spinal hemangioblastomas - conus medullaris and the
cervicomedullary junction are most common sites.
Endolymphatic sac tumors - 10% to 15
• Sometimes they are bilateral.
• Symptoms - abrupt change in hearing accompanying
hemorrhage or vertigo and tinnitus

51. • Magnetic resonance imaging
showing multiple cerebellar
hemangioblastomas

52. OCULAR FEATURES
Retinal hemangioblastomas
• Seen in 50-60%
• 50% multiple
• Usually asymptomatic
• Hemorrhage leading to
retinal injury and detachment,
• Glaucoma, uveitis, macular
edema, and sympathetic
ophthalmitis.

53. SYSTEMIC FEATURES
• Renal Cysts - present in more than half of individuals
• RCC- develops in more than 70% of patients and is the leading
cause of death.
• Pheochromocytoma - occur in 7% to 19% , may be bilateral
and occur outside the adrenal glands.
• Cyst adenomas of pancreas and epididymis

54. SCREENING PROTOCOL

55. HEREDITARYHEMORRHAGIC
TELANGIECTASIA
• Also known as Rendu-Osler-Weber syndrome or Osler-Weber-
Rendu syndrome
• Highly penetrant autosomal dominant disorder
• Characterized by telangiectasias of the skin, mucous
membranes, and various internal organs.
• Prevalence is 1 in 10,000.
• Absence of elastic fibers and smooth muscles leads to
telangiectasia in the arteriovenous anastomotic region.

56. Two genes
• Chromosome 9q33-34 (HHT1) encodes for endoglin, a TGF-β
binding protein.
• Chromosome 12q13 (HHT2), encodes for activin A receptor
type II-like 1 kinase, or ACVRL1.
• 30% of cases arise from spontaneous mutations.

57. CURAÇAO’SDIAGNOSTICCRITERIAFORHEREDITARY
HEMORRHAGICTELANGIECTASIA
Diagnosis of HHT
• Definite: 3 criteria are present
• Possible or suspected: 2 criteria are present
• Unlikely: < 2criteria are present

58. • 1. Epistaxis: spontaneous, recurrent nose bleeds
• 2. Telangiectases: multiple, at characteristic sites (lips, oral
cavity, fingers, nose)
• 3. Visceral lesions such as gastrointestinal telangiectasia (with
or without bleeding), pulmonary arteriovenous malformation
(AVM), hepatic AVM, cerebral AVMs, spinal AVM
• 4. Family history: a first degree relative with HHT according to
these criteria

59. CUTANEOUS FEATURES
Cutaneous telangiectasias
• Occur on the face, lips, and
hands
• Telangiectasias of the nasal
mucosa often cause epistaxis
• One-third of patients have
conjunctival telangiectasias,
and 10% have retinal vascular
malformations

60. SYSTEMIC FEATURES
• Widespread vascular dysplasia - lungs, gastrointestinal tract, or
genitourinary system,
• Hemoptysis, hematemesis, melena, or hematuria.
• Pulmonary arteriovenous malformations (AVMs) occur in 15%
to 20% of patients.

61. NEUROLOGICALFEATURES
• Headache, dizziness, and seizures.
• Paradoxical embolism with stroke, intraparenchymal or
subarachnoid hemorrhage.
• Meningitis or brain abscess - 1% develops cerebral abscess or
meningitis, probably because septic microemboli bypass the
normal filtration of the pulmonary circulation via a pulmonary
AVF.

62. • AVMs, high-flow pial fistulae, and telangiectasias , cavernous
malformations, venous angiomas, and vein of Galen
malformations
• Screening should begin with MRI and MR angiography (MRA)
of the brain - every 5 years

63. HYPOMELANOSIS OF ITO
• Incontinentia pigmenti achromians
• Heterogeneous and complex neurocutaneous disorder affecting
skin, brain, eye, skeleton, and other organs.
• Third most frequent neurocutaneous disease after NF1 and
tuberous sclerosis complex.
• HI is usually a sporadic disorder

64. CUTANEOUS FEATURES
Hypopigmented whorls,
streaks, and patches
• Present at birth and tend to
follow Blaschko lines,
• Usually multiple, involve
several body segments
• Unilateral or bilateral.
• Café-au-lait spots, cutis
marmorata, aplasia cutis,
nevus of Ota, trichorrhexis,
focal hypertrichosis, and nail
dystrophy.

65. NEUROLOGICALFEATURES
• Neurological abnormalities - 50% to 80%
• Seizures - Approximately half of patients with HI have seizures,
usually with onset in the first year of life. Focal seizures are
most common.
• Intellectual disability
• Macrocephaly

66. IMAGING
• Generalized cerebral or cerebellar hypoplasia
• Neuronal migration anomalies, hemimegalencephaly, and
lissencephaly.
• Extensive periventricular white-matter lesions , Small
periventricular cysts and gray-matter heterotopias
• About a third of patients with HI have normal cranial MRI
studies.

67. SYSTEMIC FEATURES
• Seen in 50% to 70% of patients
1. Ocular - microphthalmia, heterochromia iridis,
dacryostenosis, pannus, corneal opacities, cataract, optic
atrophy, retinal detachment, and pigmentation anomalies of
the retina.
2. Musculoskeletal anomaly – hemihypertrophy, short stature,
pectus carinatum and excavatum, cleft palate, butterfly
vertebrae, scoliosis, and clinodactyly and polysyndactyly.
3. Dental anomalies- conical or hypoplastic teeth, hypoplastic
dental enamel, and cleft lip and palate.
4. Cardiac defects - tetralogy of Fallot, pulmonary stenosis, and
septal defects.

68. INCONTINENTIAPIGMENTI (Bloch-Sulzberger
syndrome)
• Rare X-linked dominant condition affecting the skin, eyes, and
CNS.
• Female >>male

69. CUTANEOUS FEATURES
• Characteristic pigmentation occurs on the skin.
• Clinically classified into 4 stages.
1. Inflammatory stage (blister)- neonatal period
2. Verrucous stage - infancy
3. Pigmented stage - childhood and adulthood
4. Regression stage (atrophic and hypopigmented)

70. • Blisterlike and verrucous
stage
• Hyperpigmented stage

71. OCULAR FEATURES
• Develop in about one third cases.
• Strabismus is most common followed in frequency by cataract,
glioma and microphthalmos.
• Increased risk of retinal detachment -most likely to occur in
early childhood.

72. NEUROLOGICALFEATURES
• Seizures.
• Most affected females have normal intelligence.
• Affected males are more likely to have developmental delay.
• Neurological abnormalities are more likely to occur in
individuals with ocular abnormalities.
• Some demonstrate cerebral or cerebellar atrophy.

73. ATAXIA-TELANGIECTASIA
• Autosomal recessive disorder,
• Gene associated with AT (ATM) is a large gene located at
chromosome 11q22-23,
• Prevalence - 1 in 40,000 to 1 in 100,000.
• Begins in early childhood as a slowly progressive ataxia.
• Telangiectasias (dilated small blood vessels),
immunodeficiency, and cellular sensitivity to ionizing radiation
develop later.

74. CUTANEOUS FEATURES
• Telangiectasias - develop at age of 3 to 6 years, well after the
onset of ataxia.
• Hypertrichosis and occasional gray hairs.
• Progeric changes such as poikiloderma, loss of subcutaneous
fat, and sclerosis
• Abnormal radiosensitivity- basal cell carcinomas in young
• Cutaneous granulomas

76. NEUROLOGICALFEATURES
• Ataxia - first manifestation of AT, appears in the second year of
life.
• Truncal ataxia predominates, require a wheelchair by the age of
12 years.
• Limb ataxia, intention tremor, and segmental myoclonus
• Choreoathetosis , Progressive dystonia of the fingers may
appear in second and third decades of life.
• Abnormal eye movements - impaired voluntary ocular motility;
nystagmus and apraxias of voluntary gaze such as disorders of
smooth pursuit and limitation of upgaze
• Progressive distal muscular atrophy and fasciculations,
• Loss of vibration and position sense

77. IMMUNODEFICIENCYAND CANCER RISK
• 10% to 15% of patients with AT develop a lymphoid
malignancy by early adulthood.
• T-cell malignancies are more common than B-cell tumors
• Dysgerminoma, gastric carcinoma, liver carcinoma,
retinoblastoma, and pancreatic carcinoma.
• Nonlymphoid tumors, primarily carcinomas, represent
approximately 20% of all malignancies.
• Cerebellar astrocytoma, medulloblastoma, and glioma
• Frequent sinopulmonary infection- Recurrent or chronic
sinusitis, bronchitis, pneumonia, and chronic progressive
bronchiectasis

78. LABORATORYDIAGNOSIS
• α-fetoprotein level - elevated in all patients with AT screening
diagnostic test.
• Approximately 80% have decreased serum immunoglobulin—
IgA, IgE, or IgG, especially the IgG2 subclass
• Karyotype: high incidence of chromosomal breaks, especially
on chromosome 14
• Fibroblasts can be screened in vitro for x-ray sensitivity and
radioresistant DNA synthesis
• Brain imaging - cerebellar atrophy.

79. TREATMENT
• Supportive, no effective treatment to date
• Surveillance for infections and neoplasms
• Infections should be treated vigorously
• IVIG
• Minimize radiation as may induce further chromosomal damage
and lead to neoplasms
PROGNOSIS
• 67% of children die by age 20, typically from infection or
neoplasm

80. PARRY-ROMBERG SYNDROME
• Early childhood and rarely shortly after birth.
• Characterized by progressive loss of facial soft tissue, cartilage
and bone.
• Atrophic process ceases by the end of second decade of life.
• Neurological deficits include - recurrent headaches, ipsilateral
horner’s syndrome, contralateral partial seizures and
hemiparesis.
• Cranial CT can be normal or documents cerebral atrophy.

82. NEUROCUTANEOUS MELANOSIS
• Nonfamilial and occurs in both men and women.
• Large congenital melanocytic nevus, in most cases a giant hairy
pigmented nevus, is present on nearly half the trunk or multiple
congenital small melanocytic nevi disperse over the whole
body.
• CNS symptoms such as increased intracranial pressure and
secondary hydrocephalus occur. These are accompanied by
headache, vomiting, epileptic seizure and intelligence
impairment.
• Malignant melanoma often develops on the site of the body
with giant hairy nevus and leptomeninges.

84. THANKYOU

85. REFERENCES
• Bradleys Neurology in clinical Practice 7th edition
• Uptodate. Com
• Medscape. com