Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X

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Dr Mohan Z Mani

"Thank you very much for having published my article in record time.I would like to compliment you and your entire staff for your promptness, courtesy, and willingness to be customer friendly, which is quite unusual.I was given your reference by a colleague in pathology,and was able to directly phone your editorial office for clarifications.I would particularly like to thank the publication managers and the Assistant Editor who were following up my article. I would also like to thank you for adjusting the money I paid initially into payment for my modified article,and refunding the balance.
I wish all success to your journal and look forward to sending you any suitable similar article in future"



Dr Mohan Z Mani,
Professor & Head,
Department of Dermatolgy,
Believers Church Medical College,
Thiruvalla, Kerala
On Sep 2018




Prof. Somashekhar Nimbalkar

"Over the last few years, we have published our research regularly in Journal of Clinical and Diagnostic Research. Having published in more than 20 high impact journals over the last five years including several high impact ones and reviewing articles for even more journals across my fields of interest, we value our published work in JCDR for their high standards in publishing scientific articles. The ease of submission, the rapid reviews in under a month, the high quality of their reviewers and keen attention to the final process of proofs and publication, ensure that there are no mistakes in the final article. We have been asked clarifications on several occasions and have been happy to provide them and it exemplifies the commitment to quality of the team at JCDR."



Prof. Somashekhar Nimbalkar
Head, Department of Pediatrics, Pramukhswami Medical College, Karamsad
Chairman, Research Group, Charutar Arogya Mandal, Karamsad
National Joint Coordinator - Advanced IAP NNF NRP Program
Ex-Member, Governing Body, National Neonatology Forum, New Delhi
Ex-President - National Neonatology Forum Gujarat State Chapter
Department of Pediatrics, Pramukhswami Medical College, Karamsad, Anand, Gujarat.
On Sep 2018




Dr. Kalyani R

"Journal of Clinical and Diagnostic Research is at present a well-known Indian originated scientific journal which started with a humble beginning. I have been associated with this journal since many years. I appreciate the Editor, Dr. Hemant Jain, for his constant effort in bringing up this journal to the present status right from the scratch. The journal is multidisciplinary. It encourages in publishing the scientific articles from postgraduates and also the beginners who start their career. At the same time the journal also caters for the high quality articles from specialty and super-specialty researchers. Hence it provides a platform for the scientist and researchers to publish. The other aspect of it is, the readers get the information regarding the most recent developments in science which can be used for teaching, research, treating patients and to some extent take preventive measures against certain diseases. The journal is contributing immensely to the society at national and international level."



Dr Kalyani R
Professor and Head
Department of Pathology
Sri Devaraj Urs Medical College
Sri Devaraj Urs Academy of Higher Education and Research , Kolar, Karnataka
On Sep 2018




Dr. Saumya Navit

"As a peer-reviewed journal, the Journal of Clinical and Diagnostic Research provides an opportunity to researchers, scientists and budding professionals to explore the developments in the field of medicine and dentistry and their varied specialities, thus extending our view on biological diversities of living species in relation to medicine.
‘Knowledge is treasure of a wise man.’ The free access of this journal provides an immense scope of learning for the both the old and the young in field of medicine and dentistry as well. The multidisciplinary nature of the journal makes it a better platform to absorb all that is being researched and developed. The publication process is systematic and professional. Online submission, publication and peer reviewing makes it a user-friendly journal.
As an experienced dentist and an academician, I proudly recommend this journal to the dental fraternity as a good quality open access platform for rapid communication of their cutting-edge research progress and discovery.
I wish JCDR a great success and I hope that journal will soar higher with the passing time."



Dr Saumya Navit
Professor and Head
Department of Pediatric Dentistry
Saraswati Dental College
Lucknow
On Sep 2018




Dr. Arunava Biswas

"My sincere attachment with JCDR as an author as well as reviewer is a learning experience . Their systematic approach in publication of article in various categories is really praiseworthy.
Their prompt and timely response to review's query and the manner in which they have set the reviewing process helps in extracting the best possible scientific writings for publication.
It's a honour and pride to be a part of the JCDR team. My very best wishes to JCDR and hope it will sparkle up above the sky as a high indexed journal in near future."



Dr. Arunava Biswas
MD, DM (Clinical Pharmacology)
Assistant Professor
Department of Pharmacology
Calcutta National Medical College & Hospital , Kolkata




Dr. C.S. Ramesh Babu
" Journal of Clinical and Diagnostic Research (JCDR) is a multi-specialty medical and dental journal publishing high quality research articles in almost all branches of medicine. The quality of printing of figures and tables is excellent and comparable to any International journal. An added advantage is nominal publication charges and monthly issue of the journal and more chances of an article being accepted for publication. Moreover being a multi-specialty journal an article concerning a particular specialty has a wider reach of readers of other related specialties also. As an author and reviewer for several years I find this Journal most suitable and highly recommend this Journal."
Best regards,
C.S. Ramesh Babu,
Associate Professor of Anatomy,
Muzaffarnagar Medical College,
Muzaffarnagar.
On Aug 2018




Dr. Arundhathi. S
"Journal of Clinical and Diagnostic Research (JCDR) is a reputed peer reviewed journal and is constantly involved in publishing high quality research articles related to medicine. Its been a great pleasure to be associated with this esteemed journal as a reviewer and as an author for a couple of years. The editorial board consists of many dedicated and reputed experts as its members and they are doing an appreciable work in guiding budding researchers. JCDR is doing a commendable job in scientific research by promoting excellent quality research & review articles and case reports & series. The reviewers provide appropriate suggestions that improve the quality of articles. I strongly recommend my fraternity to encourage JCDR by contributing their valuable research work in this widely accepted, user friendly journal. I hope my collaboration with JCDR will continue for a long time".



Dr. Arundhathi. S
MBBS, MD (Pathology),
Sanjay Gandhi institute of trauma and orthopedics,
Bengaluru.
On Aug 2018




Dr. Mamta Gupta,
"It gives me great pleasure to be associated with JCDR, since last 2-3 years. Since then I have authored, co-authored and reviewed about 25 articles in JCDR. I thank JCDR for giving me an opportunity to improve my own skills as an author and a reviewer.
It 's a multispecialty journal, publishing high quality articles. It gives a platform to the authors to publish their research work which can be available for everyone across the globe to read. The best thing about JCDR is that the full articles of all medical specialties are available as pdf/html for reading free of cost or without institutional subscription, which is not there for other journals. For those who have problem in writing manuscript or do statistical work, JCDR comes for their rescue.
The journal has a monthly publication and the articles are published quite fast. In time compared to other journals. The on-line first publication is also a great advantage and facility to review one's own articles before going to print. The response to any query and permission if required, is quite fast; this is quite commendable. I have a very good experience about seeking quick permission for quoting a photograph (Fig.) from a JCDR article for my chapter authored in an E book. I never thought it would be so easy. No hassles.
Reviewing articles is no less a pain staking process and requires in depth perception, knowledge about the topic for review. It requires time and concentration, yet I enjoy doing it. The JCDR website especially for the reviewers is quite user friendly. My suggestions for improving the journal is, more strict review process, so that only high quality articles are published. I find a a good number of articles in Obst. Gynae, hence, a new journal for this specialty titled JCDR-OG can be started. May be a bimonthly or quarterly publication to begin with. Only selected articles should find a place in it.
An yearly reward for the best article authored can also incentivize the authors. Though the process of finding the best article will be not be very easy. I do not know how reviewing process can be improved. If an article is being reviewed by two reviewers, then opinion of one can be communicated to the other or the final opinion of the editor can be communicated to the reviewer if requested for. This will help one’s reviewing skills.
My best wishes to Dr. Hemant Jain and all the editorial staff of JCDR for their untiring efforts to bring out this journal. I strongly recommend medical fraternity to publish their valuable research work in this esteemed journal, JCDR".



Dr. Mamta Gupta
Consultant
(Ex HOD Obs &Gynae, Hindu Rao Hospital and associated NDMC Medical College, Delhi)
Aug 2018




Dr. Rajendra Kumar Ghritlaharey

"I wish to thank Dr. Hemant Jain, Editor-in-Chief Journal of Clinical and Diagnostic Research (JCDR), for asking me to write up few words.
Writing is the representation of language in a textual medium i e; into the words and sentences on paper. Quality medical manuscript writing in particular, demands not only a high-quality research, but also requires accurate and concise communication of findings and conclusions, with adherence to particular journal guidelines. In medical field whether working in teaching, private, or in corporate institution, everyone wants to excel in his / her own field and get recognised by making manuscripts publication.


Authors are the souls of any journal, and deserve much respect. To publish a journal manuscripts are needed from authors. Authors have a great responsibility for producing facts of their work in terms of number and results truthfully and an individual honesty is expected from authors in this regards. Both ways its true "No authors-No manuscripts-No journals" and "No journals–No manuscripts–No authors". Reviewing a manuscript is also a very responsible and important task of any peer-reviewed journal and to be taken seriously. It needs knowledge on the subject, sincerity, honesty and determination. Although the process of reviewing a manuscript is a time consuming task butit is expected to give one's best remarks within the time frame of the journal.
Salient features of the JCDR: It is a biomedical, multidisciplinary (including all medical and dental specialities), e-journal, with wide scope and extensive author support. At the same time, a free text of manuscript is available in HTML and PDF format. There is fast growing authorship and readership with JCDR as this can be judged by the number of articles published in it i e; in Feb 2007 of its first issue, it contained 5 articles only, and now in its recent volume published in April 2011, it contained 67 manuscripts. This e-journal is fulfilling the commitments and objectives sincerely, (as stated by Editor-in-chief in his preface to first edition) i e; to encourage physicians through the internet, especially from the developing countries who witness a spectrum of disease and acquire a wealth of knowledge to publish their experiences to benefit the medical community in patients care. I also feel that many of us have work of substance, newer ideas, adequate clinical materials but poor in medical writing and hesitation to submit the work and need help. JCDR provides authors help in this regards.
Timely publication of journal: Publication of manuscripts and bringing out the issue in time is one of the positive aspects of JCDR and is possible with strong support team in terms of peer reviewers, proof reading, language check, computer operators, etc. This is one of the great reasons for authors to submit their work with JCDR. Another best part of JCDR is "Online first Publications" facilities available for the authors. This facility not only provides the prompt publications of the manuscripts but at the same time also early availability of the manuscripts for the readers.
Indexation and online availability: Indexation transforms the journal in some sense from its local ownership to the worldwide professional community and to the public.JCDR is indexed with Embase & EMbiology, Google Scholar, Index Copernicus, Chemical Abstracts Service, Journal seek Database, Indian Science Abstracts, to name few of them. Manuscriptspublished in JCDR are available on major search engines ie; google, yahoo, msn.
In the era of fast growing newer technologies, and in computer and internet friendly environment the manuscripts preparation, submission, review, revision, etc and all can be done and checked with a click from all corer of the world, at any time. Of course there is always a scope for improvement in every field and none is perfect. To progress, one needs to identify the areas of one's weakness and to strengthen them.
It is well said that "happy beginning is half done" and it fits perfectly with JCDR. It has grown considerably and I feel it has already grown up from its infancy to adolescence, achieving the status of standard online e-journal form Indian continent since its inception in Feb 2007. This had been made possible due to the efforts and the hard work put in it. The way the JCDR is improving with every new volume, with good quality original manuscripts, makes it a quality journal for readers. I must thank and congratulate Dr Hemant Jain, Editor-in-Chief JCDR and his team for their sincere efforts, dedication, and determination for making JCDR a fast growing journal.
Every one of us: authors, reviewers, editors, and publisher are responsible for enhancing the stature of the journal. I wish for a great success for JCDR."



Thanking you
With sincere regards
Dr. Rajendra Kumar Ghritlaharey, M.S., M. Ch., FAIS
Associate Professor,
Department of Paediatric Surgery, Gandhi Medical College & Associated
Kamla Nehru & Hamidia Hospitals Bhopal, Madhya Pradesh 462 001 (India)
E-mail: drrajendrak1@rediffmail.com
On May 11,2011




Dr. Shankar P.R.

"On looking back through my Gmail archives after being requested by the journal to write a short editorial about my experiences of publishing with the Journal of Clinical and Diagnostic Research (JCDR), I came across an e-mail from Dr. Hemant Jain, Editor, in March 2007, which introduced the new electronic journal. The main features of the journal which were outlined in the e-mail were extensive author support, cash rewards, the peer review process, and other salient features of the journal.
Over a span of over four years, we (I and my colleagues) have published around 25 articles in the journal. In this editorial, I plan to briefly discuss my experiences of publishing with JCDR and the strengths of the journal and to finally address the areas for improvement.
My experiences of publishing with JCDR: Overall, my experiences of publishing withJCDR have been positive. The best point about the journal is that it responds to queries from the author. This may seem to be simple and not too much to ask for, but unfortunately, many journals in the subcontinent and from many developing countries do not respond or they respond with a long delay to the queries from the authors 1. The reasons could be many, including lack of optimal secretarial and other support. Another problem with many journals is the slowness of the review process. Editorial processing and peer review can take anywhere between a year to two years with some journals. Also, some journals do not keep the contributors informed about the progress of the review process. Due to the long review process, the articles can lose their relevance and topicality. A major benefit with JCDR is the timeliness and promptness of its response. In Dr Jain's e-mail which was sent to me in 2007, before the introduction of the Pre-publishing system, he had stated that he had received my submission and that he would get back to me within seven days and he did!
Most of the manuscripts are published within 3 to 4 months of their submission if they are found to be suitable after the review process. JCDR is published bimonthly and the accepted articles were usually published in the next issue. Recently, due to the increased volume of the submissions, the review process has become slower and it ?? Section can take from 4 to 6 months for the articles to be reviewed. The journal has an extensive author support system and it has recently introduced a paid expedited review process. The journal also mentions the average time for processing the manuscript under different submission systems - regular submission and expedited review.
Strengths of the journal: The journal has an online first facility in which the accepted manuscripts may be published on the website before being included in a regular issue of the journal. This cuts down the time between their acceptance and the publication. The journal is indexed in many databases, though not in PubMed. The editorial board should now take steps to index the journal in PubMed. The journal has a system of notifying readers through e-mail when a new issue is released. Also, the articles are available in both the HTML and the PDF formats. I especially like the new and colorful page format of the journal. Also, the access statistics of the articles are available. The prepublication and the manuscript tracking system are also helpful for the authors.
Areas for improvement: In certain cases, I felt that the peer review process of the manuscripts was not up to international standards and that it should be strengthened. Also, the number of manuscripts in an issue is high and it may be difficult for readers to go through all of them. The journal can consider tightening of the peer review process and increasing the quality standards for the acceptance of the manuscripts. I faced occasional problems with the online manuscript submission (Pre-publishing) system, which have to be addressed.
Overall, the publishing process with JCDR has been smooth, quick and relatively hassle free and I can recommend other authors to consider the journal as an outlet for their work."



Dr. P. Ravi Shankar
KIST Medical College, P.O. Box 14142, Kathmandu, Nepal.
E-mail: ravi.dr.shankar@gmail.com
On April 2011
Anuradha

Dear team JCDR, I would like to thank you for the very professional and polite service provided by everyone at JCDR. While i have been in the field of writing and editing for sometime, this has been my first attempt in publishing a scientific paper.Thank you for hand-holding me through the process.


Dr. Anuradha
E-mail: anuradha2nittur@gmail.com
On Jan 2020

Important Notice

Case Series
Year : 2023 | Month : May | Volume : 17 | Issue : 5 | Page : SR01 - SR05 Full Version

Facial Neurocutaneous Markers and their Clinical Profile- A Case Series


Published: May 1, 2023 | DOI: https://doi.org/10.7860/JCDR/2023/62396.17868
Bibekananda Mukherjee, Barnali Das, Joydeep Das

1. Assistant Professor, Department of Paediatrics, Jagannath Gupta Institute of Medical Sciences and Hospital, Kolkata, West Bengal, India. 2. Assistant Professor, Department of Paediatrics, Institute of Child Health (ICH), Kolkata, West Bengal, India. 3. Professor and Head, Department of Paediatrics, Jagannath Gupta Institute of Medical Sciences and Hospital, Kolkata, West Bengal, India.

Correspondence Address :
Bibekananda Mukherjee,
Flat No. 1E-102, Alaktika Housing Complex, Action Area-2, Newtown, Near City Centre 2 Mall, North 24 Parganas, Kolkata, West Bengal, India.
E-mail: bmtata@gmail.com

Abstract

Cutaneous birthmarks are a heterogeneous group of congenital skin lesions with high diagnostic value. A good clinician, by looking at the skin, eyes, and face, can diagnose conditions like Neurofibromatosis type 1 (NF1), Tuberous Sclerosis Complex (TSC), Ataxia-telangiectasia, Von Hippel-Lindau disease, Sturge-Weber Syndrome (SWS), and others. The author reports, in the present case series, six cases presenting with one or more of the following seven different types of facial neurocutaneous markers like Café-au-lait Macules (CALM), neurofibromas, facial angiofibromas, forehead plaque, hypomelanotic macules (ash-leaf) on the trunk and extremities, capillary malformation in the face (port-wine stain), and ocular telangiectasia. Using these cutaneous markers as red alerts, the authors did a focused clinical examination, ophthalmic and auditory evaluation, neuroimaging, renal and cardiac evaluation to come to a diagnosis. This helped us in detecting clinical syndromes like NF1, TSC, SWS, and unveiled the hidden morbidities like hypertension, intracranial tumours, intracardiac rhabdomyoma, glaucoma, and other ocular abnormalities. The present case series emphasises the need for all paediatricians and ophthalmologists to develop a clinical eye to identify neurocutaneous markers in children who may arrive at their clinic with various problems for early diagnosis and treatment of various neurocutaneous syndromes and their co-morbidities.

Keywords

Ash-leaf Macule, Café-au-lait spot, Haemangioma, Neurocutaneous markers, Telangiectasia

The embryogenesis of the central nervous system is initiated from the ectoderm. The ectoderm is further specialised as the surface ectoderm, which differentiates into the epidermis, nails, and hair, and the neural ectoderm, which gives rise to the neural tube and neural crest, which subsequently give rise to the brain, spinal cord, and peripheral nerves (1). The neurocutaneous syndromes include a heterogeneous group of disorders characterised by abnormalities of both the integument and central nervous system of variable severity. Many of the disorders are inherited and believed to arise from a defect in differentiation of the primitive ectoderm (nervous system, eyeball, retina, and skin) (2). The various cutaneous markers, which are present since birth or appearing after birth like vascular malformation, nevus, café-au-lait spots, neurofibroma, ash-leaf macule, ocular telangiectasia, and others, are very important clinical pointers to underlying abnormalities in other major organs like the brain, spinal cord, eyes, kidneys, and heart (3),(4),(5).

Case Report

Case 1

A five-year-old male child reported with progressive headache and difficulty in vision without any seizures. The visual acuity of the right eye was reduced for both distant and near vision. On examination, there were 11 CALM over the face, trunk, and limbs varying from 7×4 mm to 11×5 mm sizes. He had multiple neurofibromas over hands and feet. He also had a facial plaque (Table/Fig 1)a. Blood pressure was found to be more than 95th centile according to age, height, and sex and was treated with antihypertensive medication. His mother was found to have multiple neurofibromas all over the body, and his elder sister was found to have a few CALM. The slit lamp examination of the eye showed multiple iris lisch nodules in both eyes. Magnetic Resonance Imaging (MRI) of the brain was done, which showed a large optic glioma arising from the right optic nerve with enlargement of the orbit and sphenoid wing dysplasia (Table/Fig 1)b. The diagnosis of NF1 was established due to the presence of CALM (six or more CALM >5 mm in the greatest diameter in prepubertal individuals), neurofibroma, iris Lisch nodules, positive family history, and optic glioma and sphenoid wing dysplasia (6). The child was referred to a neurosurgeon. His renal and adrenal ultrasound and renal artery doppler were normal. Echocardiography was also found to be normal. Hearing assessment was also normal. The child was started on antihypertensive medication- amlodipine and was immediately referred to a neurosurgeon and eye surgeon for surgical management of optic glioma.

Case 2

An eight-month-old female baby reported with a superficial lesion over the right temple with a deep red, pebbly surfaced lesion which was having an irregular margin measuring about 10×5 cm. The lesion was blanching on pressure and consistent with strawberry haemangioma (Table/Fig 2). The mother also noticed watering from the right eye, and the child was avoiding bright light. No other skin lesions were found. The child had achieved normal growth and development for age. Based on the erythematous progressively enlarging large skin lesion over the right ophthalmic dermatome (V1) of the Trigeminal nerve and its clinical course, the possibility of SWS was high (7),(8). Ophthalmic examination revealed increased Intraocular Pressure (IOP) on the right eye (IOP 22 mmHg in the right eye vs 12 mmHg in the left eye) and choroidal vascular malformation. Anti-glaucoma medications were started with a plan for surgical intervention in follow-up. MRI brain was normal. Ultrasound abdomen was done which revealed no haemangioma, elsewhere. Oral propranolol was started at a dose of 1 mg/kg/day and skin lesion significantly regressed in size after three months. The child is currently under ophthalmological follow-up.

Case 3

A 4-year-old male child reported with status epilepticus, which was controlled with multiple antiepileptic medications. There was no previous history of seizures apart from autistic behaviour. The child had uneventful perinatal history and had achieved normal developmental milestones. On examination of face three well-defined areas of hypopigmentation without any superficial scaling measuring approximately 1.5 cm (maximum in longitudinal axis), was found suggestive of ash-leaf macule. Wood’s lamp examination did not reveal any fluorescence. He also had five ash-leaf macules measuring 1.5 to 2 cm in longitudinal axis on the trunk. Neurological examination was normal. Blood pressure was normal for age. On fundoscopy, few tiny white depigmented patches were found in the left eye (ocular ash-leaf). Visual acuity test was normal in both eyes. Magnetic Resonance Imaging (MRI) brain showed multiple subependymal nodules and cortical tuber (Table/Fig 3)b. Electroencephalography (EEG) showed hypsarrhythmia (high-voltage, asynchronous slow waves) (Table/Fig 3)c. Ultrasonography did not reveal any kidney abnormalities. Echocardiograpy (ECHO) revealed a mass in the left ventricle suggestive to be cardiac rhabdomyoma (Table/Fig 3)d. Child was kept under regular follow-up for cardiac evaluation. Electrocardiogram (ECG) was normal. No other members in the family were found to have similar lesions. The diagnosis of TSC was established by presence of major criteria’s like presence of ash-leaf macules more than three with ocular version, cortical tubers and subependymal nodule in MRI (9). The s were treated with three antiepileptic drugs. This child was initially started on Levetiracetam at the dose of 10 mg/kg/day and gradually increased to 20 mg/kg/day and Clobazam at the dose of 0.5 mg/kg /day. After neuroimaging, vigabatrin was advised but parents could not afford due to financial reasons. So, the child was started on prednisolone (4 mg/kg/day for two weeks and gradually tapered over next six weeks) to which the child responded well. He was then continued on Levetiracetam and clobazam. Seizures are well-controlled now and are under neurological follow-up.

Case 4

A 15-year-old female reported with global developmental delay and refractory seizures on multiple antiepileptic drugs. Examination of face showed multiple angiofibromas suggestive of adenoma sebeceum sparing the forehead and a forehead plaque (Table/Fig 4). In the present case cutaneous ash-leaf macule or any other skin marker was not detected on Wood’s lamp examination. Fundoscopy revealed retinal mulberry tumour. Vision was normal. EEG showed hypsarrhythmia. MRI showed multiple subependymal nodules and cortical tubers, however, there was no ventriculomegaly. Echocardiography did not reveal any cardiac mass. Renal ultrasound was also normal. The diagnosis of TSC was established by the presence of five major criterias like facial angiofibroma (adenoma sebaceum), forehead plaque, MRI showing subependymal nodules with cortical tubers and retinal nodular hamartoma. Seizures were controlled with vigabatrin. The child was started on vigabatrin at the dose of 50 mg/kg/day in two divided doses. Seizures were not well-controlled at this dose, so, the dose had to be escalated to 75 mg/kg/day after two weeks and advised to continue it for six months and be under strict follow-up with paediatric neurologist.

Case 5

A 7-year-old female child reported with history of falls and clumsiness, while walking. She had recurrent history of cough and cold since birth and frequent diarrhoeal episodes. Mother had noticed a change in hand writing and frequent falling of objects from hand for last few months. On examination her weight and height were in the 3rd centiles. She had lost 3 kg weight in last two years. There was no history of contact with tuberculosis and sputum for GeneXpert was negative. She was found to have ataxic gait and poor coordination in hands and she was turning her head (somewhat more than normal), when she wanted to look at the sides. There was a telangiectatic lesion on left eye which mother noticed for last two years. Ophthalmologists confirmed that there was telangiectasis over sclera with oculomotor apraxia (Table/Fig 5). Fundal examination was normal. MRI brain showed white matter signal changes in lower brain stem and cervical cord suggestive of degenerative ataxia. The diagnosis of ataxia-telangiectasia was made based on gait ataxia, ocular telangiectasia and MRI findings of white matter changes in brain (6). Suspecting ataxia-telangiectasia serum Immunoglobulin A (IgA) level and Alpha Fetoprotein (AFP) estimation revealed low serum IgA level and very high AFP levels. So, a diagnosis of Ataxia Telangiectasia was made and genetic test was advised. Parents were counselled and the child was advised to avoid unnecessary exposure to ionising radiation (X-ray, CT scan).

Case 6

A 9-month-old female child presented with developmental delay and reddish blue discolouration of skin involving right half of face, right hand and right leg. There was also mild hypertrophy of the right leg compared to the left (Table/Fig 6)a. Ophthalmological examination revealed glaucoma in the right eye. MRI of brain showed right cerebral hemiatrophy, hypertrophied choroids plexuses, left parieto-occipital gliosis with marked leptomeningeal enhancement along left parieto-occipital gyri (Table/Fig 6)b. The child was started on antiglaucoma medications and prophylactic anticovulsant. The child was also started on propranolol 1 mg/kg/day. A few months later the child came to emergency with intractable seizures mostly involving left half of body followed by left-sided hemiparesis, but the skin lesions had become fainter and were regressing. In this case the diagnosis of SWS (Type I Roach scale) was made based on the constellation of symptoms and signs of capillary malformation in the face (port-wine stain) and brain abnormalities (leptomeningeal) and glaucoma (4),(7). Parents were counselled regarding the prognosis and kept on follow-up with antiepileptic medications.

Discussion

Dermatological examination is a very important clue for diagnosing different diseases of brain, as embryologically both structures arise from same neural crest (1),(2). In the present case series, the varied skin changes found in six children, which were present since birth or had appeared after birth like vascular malformation, nevus, CALM, neurofibroma, facial plaques, port-wine stain, ash-leaf macule in face, trunk or limbs were pointers to underlying syndromes (Table/Fig 7). These various cutaneous markers were associated with MRI brain abnormalities in 83% (5 out of 6 cases) against 62-93% reported in other studies (3). In the present series, 83% of cases (5 out of 6 cases) with cutaneous markers having ophthalmological findings in form of raised IOP, abnormal vasculature, retinal abnormalities supporting the need for detailed ophthalmological evaluation in every child with cutaneous marker (30-70% reported in other studies) was observed (4). In one case, authors could find a cardiac mass probably rhabdomyoma because it was a case of tuberous sclerosis (50% reported in other cases) (5).

The neurocutaneous syndromes which have been discussed in our case series are NF1, TSC, SWS, ataxia telangiectasia. The diagnosis of these is essentially clinical based on set diagnostic criteria (6),(7),(8). Genetic diagnosis may help to confirm those cases, where one cannot come to definite conclusion based on clinical evidence. All these cases being genetically transmitted, pedigree tracing again plays a very important part of history apart from thorough focused clinical examination. Follow-up of these children involve paediatrician, ophthalmologist, audiologist, cardiologist and neurologist. Genetic counselling plays an important role in these inherited conditions and also, antenatal advices to the mother (10).

The NF1 has an incidence of 1 in 3,000 live births and is caused by autosomal dominant loss-of-function mutations in the NF1 gene (6). Approximately, 50% are inherited from an affected parent, and the other 50% result from a sporadic gene mutation (11),(12). The condition is clinically diagnosed when any two of the following seven features are present: (a) six or more CALM >5 mm in greatest diameter in prepubertal individuals and > 15 mm in greatest diameter in postpubertal individuals in almost 100% of patients; (b) Axillary oringuinal freckling; (c) Two or more iris Lisch nodules from only 5% of children younger than three year of age, to 42% among children 3-4 year of age; (d) Two or more neurofibromas; (e) A distinctive osseous lesion such as sphenoid dysplasia (which may cause pulsating exophthalmos) or cortical thinning of long bones with or without pseudoarthrosis (most often the tibia); (f) Optic gliomas are present in approximately 15-20% of individuals with NF1 (g) A first-degree relative with NF1. In Case 1 of the present series, six criteria were fulfilled. One child had hypertension in addition, which in a case of NF1 can be due to renal artery stenosis or phaeochromocytoma (6). These children in additionally have certain behavioural issues like attention deficit hyperactivity.

In the two cases number 2 and 6 of the present series, SWS Type I (Roach Scale) was diagnosed, as both facial and leptomeningeal angiomas were present with glaucoma. Literatures report that only 20-50 % of children with port-wine stain lesions involving the forehead and upper eyelid have SWS, especially, if it is in the distribution of ophthalmic division of the trigeminal nerve (4). There may be ipsilateral involvement of the brain too. Seizures occur in 75-80% of SWS cases (4). Early diagnosis and treatment will reduce neurologic sequelae and prevent blindness (7). Although port-wine stain has high localising value, up to 30% of cases has leptomengial involvement [9,13]. In Case 2, there was isolated facial lesion with glaucoma of ipsilateral eye without any cerebral involvement, but in Case 6 there was cerebral involvement, as well, with seizures and hemiparesis.

There were two cases (Case 3 and 4) of TSC in the present series fulfilling the diagnostic criterias. Case 3 had four major (hypomelanotic macules, cardiac rhabdomyoma, subependymal nodules and cortical tubers) and one minor (retinal achromatic patch) features. Case 4 had five major features (facial angiofibroma, forehead plaque, retinal noduler hamartomas, cortical dysplasias like cortical tubers and subependymal nodules). Presence of two major features or one major feature, plus two or more minor features is diagnostic of TSC (14). Forehead plaque, mostly present at birth and detectable early in life is a good cutaneous marker for prediction of ipsilateral intracranial abnormalities (6). Similarly facial ash-leaf macules in face and other areas of body have associated central nervous system, kidney diseases and other abnormalities (6). TSC may have a varied spectrum of presentation. It may present to a paediatrician with refractory seizures and global developmental delay on one hand, whereas, it may remain asymptomatic with only skin manifestations on the other hand (14).

In ataxia telangiectasia, the most prominent clinical features are progressive cerebellar ataxia, oculocutaneous telangiectasias, chronic sinopulmonary disease, a high incidence of malignancy and variable humoral and cellular immunodeficiency (13). Telangiectasia are visible small blood vessels (capillaries, venules and arterioles) over skin and mucosa are also cutaneous marker for underline hereditary disorders (12),(13). In the present case series, Case 5 had all these three components ocular telangiectasias, childhood ataxia with progressive neuromotor degeneration with low IgA (reported in 50-80% of these patients) and high alpha fetoprotein (14).

Conclusion

Paediatricians should develop a clinical eye to identify neurocutaneous markers in children who may arrive at their clinic with various problems for early diagnosis of various neurocutaneous syndromes and their co-morbidities. Whenever a neurocutaneous marker like vascular malformation, nevus, CALM, neurofibroma, facial plaques, port-wine stain is detected, a detailed history, including family history, should be taken. Thorough clinical examination of all systems is necessary to avoid missing significant early signs. A detailed ophthalmic evaluation of children of all age groups with neurocutaneous markers is a must, including screening for glaucoma and early management to prevent vision loss. Neuroimaging threshold should be low, and MRI is preferred. It can reveal many abnormalities that may not be apparent clinically. The present study also highly recommends the need for regular follow-up with clinical as well as ophthalmic, neurological (including neuroimaging when required), cardiac, and renal assessment for the neurocutaneous syndromes when detected.

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DOI and Others

DOI: 10.7860/JCDR/2023/62396.17868

Date of Submission: Dec 21, 2022
Date of Peer Review: Feb 04, 2023
Date of Acceptance: Apr 01, 2023
Date of Publishing: May 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Dec 22, 2022
• Manual Googling: Mar 08, 2023
• iThenticate Software: Mar 29, 2023 (5%)

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