Pattern Of Chediak Higashi Syndrome In Egyptian Children

Menoufiya Medical Journal 

Vol. 21 No. 1 Jan2008 

169 

Pattern Of Chediak 

Aisha Marsafy et al. 

Pattern Of Chediak Higashi Syndrome In Egyptian Children: A Variant 

With Hyperpigmentation Of The Skin And A Subtle Clinical Course 

AISHA MARSAFY - JEANNET BOTROS - NERMEEN GALAL 

Department of Pediatrics 

Cairo University Specialized Pediatric Hospital 

Abstract 

Chediak Hiagshi Syndrome (CHS) is a rare immunodeficiency disorder involving 

phagocytes with autosomal recessive inheritance.CHS is characterized classically 

by hypopigmentation, recurrent infections and may progress into accelerated 

phase with lymphoma like infilteration of reticuloendothelial system. 

Objective: Study pattern of Chediak Higashi Syndrome in Egyptian children 

with different presentations as a variant with initial hyperpigmentation is 

reported. 

Methods: Cases presenting to the Clinical Immunodeficiency clinic at Cairo 

University Specialized Pediatric Hospital from 2003-2007 diagnosed with 

Chediak Higashi Syndrome (CHS) were included .Cases underwent history 

taking with emphasis on family history and consanguinity, meticulous physical 

examination and basic laboratory investigations. Results: Ten cases were 

diagnosed with CHS. Mean age of presentation was 3.1 years with a standard 

deviation of 4.9.Consanguinity was positive in 70% of cases. Clinical patterns 

showed two cases with initial generalized progressive hyperpigmentation 

followed by later fading of hair color and a benign slowly progressive bicytopenia 

(anemia and thrombocytopenia) and a subtle clinical course with no development 

into accelerated phase so far despite the bicytopenia (3 and 4 years).Conclusion: 

CHS may have confusing presentations which may delay diagnosis and decrease 

chance with BMT if feasible. 

Clinical Implications: Reporting of any similar cases to study pattern of 

progression and whether this form has a milder course over years in view of 

infections, malignancy and accelerated phase development and or different 

mutations. 

Key words: Chediak Higashi Syndrome-Primary Immunodeficiency 

Introduction: 

Chediak Higashi Syndrome (CHS) is a 

primary immunodeficiency disorder 

characterized by abnormal intracellular 

protein transport. Mode of inheritance is 

autosomal recessive. Presentations vary 

from hypopigmentation of the skin, eyes, 

and hair; prolonged bleeding times; easy 

bruisability; recurrent infections; abnormal 

natural killer cell function; and peripheral 

neuropathy. Morbidity results from patients 

succumbing to frequent bacterial infections 

or to an accelerated-phase lymphoproliferation 

into the major organs of the body. The 

MMJ (Jan 2008) Vol 21 N: 1 P 169 :164 

accelerated phase or accelerated reaction is 

a nonmalignant lymphohistiocytic 

lymphoma like infiltration of multiple 

organs that occurs in more than 80% of 

patients. This lymphoma like stage is 

precipitated by viruses, particularly by 

infection by the Epstein-Barr virus. It is 

associated with anemia, bleeding episodes, 

and overwhelming infections leading to 

death. Patients who do not develop an 

accelerated phase tend to have fewer or no 

infections, but usually develop 

progressively debilitating neurological


Vol. 21 No. 1 Jan2008 

manifestations (1, 2). Studies have 

identified mutations throughout the 

CHS1/LYST gene and may explain how it 

affects the hematological, immune and 

neurological systems by altered vesicle 

fusion or fission. (3). 

Allogenic bone marrow transplantation 

(BMT) from an HLA-matched sibling is the 

therapy of choice and should be performed 

early. If no matched family donor is 

available, an unrelated donor or a placental 

blood graft is a good alternative. BMT 

alleviates the immune problems and the 

accelerated phase, but it does not inhibit the 

development of neurological disorders, 

which become increasingly worse with age. 

BMT corrects the immunologic status but 

does not affect pigment dilution. (4) Studies 

reviewed the neurological status of 4 other 

patients with CHS who had undergone 

BMT: 1 began having gait abnormality, 

falls when walking, and decreased cognitive 

abilities at the age of 21; 3 other patients, 

aged 17, 14, and 2 years, had borderline low 

IQ scores but normal neurological 

examinations. Researchers noted that the 

neurological symptoms observed were 

identical to those in adults with mild CHS 

who did not undergo BMT, and concluded 

that the symptoms most likely resulted from 

steady long-term progression, despite BMT, 

of the lysosomal defect in neurons and glial 

cells.(5) 

METHODOLOGY: 

Cases presenting to the Clinical 

Immunodeficiency clinic at Cairo 

University Specialized Pediatric Hospital 

from 2003-2007 diagnosed with Chediak 

Higashi Syndrome (CHS) were included. 

Cases were subjected to history taking with 

emphasis on family history, consanguinity, 

presenting complaints, generalized 

symptom review. Clinical examination was 

conducted with basic anthropometric data 

and fundus examination. Basic 

investigations included a full blood count 

with comment on peripheral blood in view 

of presence of giant granules, some of the 

cases underwent bone marrow examination 

170 



and some had hair examination or skin 

biopsy according to presentation. An 

informed consent was obtained from 

participants in the study after being 

approved by the ethics committee. 

Figure 1 : Patient with CHS and 

hepatosplenomegaly with skin abscesses 

Figure 2: Patient with hyperpigmentation 

variant of CHS


Vol. 21 No. 1 Jan2008 

RESULTS: 

Ten cases were diagnosed with CHS. Mean 

age of presentation was 3.1 years with a 

standard deviation of 4.9 and an 

interquartile range of 4.7 years. There were 

6 females and 4 males. Six of the patients 

were residing in greater Cairo, two from 

Delta governorates and two referred from 

Upper Egypt. 

As for family history 4 (3 females and a 

male were siblings) with one healthy living 

female sibling. One male had history of a 

female sibling death with pneumonia, one 

female had history of male sibling death 

early in the neonatal period of unknown 

cause and lastly one female had history of 

maternal cousins' fatality early in life. 

Consanguinity was positive in seven 

children and negative in three. 

Consanguinity was of the first degree in the 

three positive families. Growth parameters 

were faltering in all of the included children 

except for the neonates who initially 

showed a normal birth weight, length and 

skull circumference. 

As for presenting symptom pneumonia was 

detected over the course of follow up in 5 

cases. Recurrent sinus infections in 2. 

Hepatosplenomegaly in 6 generalized 

lymphadenopathy in 3 and scattered deep 

abscess formation in 4 cases. Recurrent 

gingivitis and pathos formation in 2 children 

whereas one complained of chronic 

diarrhea. Interestingly 2 of the girls had an 

initial picture of generalized progressive 

hyperpigmentation (not only involving sun 

exposed areas) of the skin followed by later 

gradual fading of hair colour into silvery 

grey with no initial severe infections .As 

medical advice is sought for the 

pigmentation they get diagnosed with a 

bicytopenia( anemia and thrombocytopenia) 

for which investigations reveal CHS by 

bone marrow aspirate in one case and one 

by hair examination conducted at hospital 

Necker Des Enfants,France. Over the course 

of years they develop a hepatosplenomegaly 

that is of slow progression not accompanied 

by neither Leucopenia nor 

lymphadenopathy and characterized by a 

171 



benign course so far. The remaining 4 cases 

who complained of hepatosplenomegaly 

had a stormy course with the enlargement 

occurring over the course of days with rapid 

progression in to a full blown accelerated 

phase with pancytopenia and progressive 

organ enlargement with worsening of 

general condition. 

Screening neurological examination was 

normal in 8 cases (conducted respective to 

their age) apart from one case having 

nystagmus and one boy developing 

encephalopathy as he developed the 

accelerated phase. Fundus examination 

revealed pale fundi in 6 cases and two had 

tigroid changes. No significant changes 

could be commented on regarding dentition. 

Laboratory investigations revealed 

neutropenia in 3 cases ,bicytopenia ( anemia 

and neutropenia) in two cases and 

pancytopenia with 4 cases during the 

accelerated phase.Chatacteristic CHS 

granules were reported in 8 cases 

(peripheral blood in six and Bone marrow in 

two) .Skin biopsy conducted for two cases 

was normal apart from an exaggerated 

pattern of pigmentation. 

Cases with the accelerated phase were 

referred to National Cancer Institute for 

chemotherapy with an unfortunate outcome 

in all four cases with accelerated phase. 

Two of them were transplanted after 

induction of quiescence and died 

subsequently with complications. 

DISCUSSION: 

Chediak Higashi Syndrome though still a 

rare disorder is probably found in higher 

distribution in Egypt because of the 

consanguinity rates. We have no data about 

the exact prevalence of CHS patients but 

further study is ongoing We suggest the 

occurrence of a variant of CHS with a more 

subtle picture with generalized progressive 

hyperpigmentation contrary to the well 

known hypopigmentation and a relatively 

benign clinical course as the bicytopenia in 

both cases has lasted for 3 and 4 years till 

now without progression into accelerated 

phase and with absence of major infections.


Vol. 21 No. 1 Jan2008 

On review of literature classic CHS was 

diagnosed in African race before (5, 6).In 

another society with high consanguinity 

(Saudi Arabia) cases was reported with the 

classical presentation and a poor outcome. 

(7). A case was reported with speckled 

hypopigmentation and hyperpigmentation 

of the sun-exposed areas probably pointing 

to altered presentation in darkly pigmented 

races. (8) 

A group of Finnish patients showed 

Peripheral blood neutropenia becoming 

more profound as anemia and 

thrombocytopenia develop contrary to our 

cases (9). A study reported that About 10- 

15% of patients exhibit a much milder 

clinical phenotype and survive to adulthood, 

but develop progressive and often fatal 

neurological dysfunction .On describing the 

organization and genomic DNA sequence of 

the CHS1 gene and mutations in patients 

with severe childhood CHS, only 

functionally null mutant CHS1 alleles were 

found, whereas in patients with the 

adolescent and adult forms of CHS they 

also found missense mutant alleles that 

likely encode CHS1 polypeptides with 

partial function suggesting an allelic 

genotype-phenotype relationship among the 

various clinical forms of CHS.(10). Results 

of BMT reveal mortality was highest in 

those with accelerated phase disease at 

transplantation and after alternative related 

donor HCT (11).Unfortunately this 

treatment modality is not always feasible in 

our cases as haploidential donors are needed 

and some children may have no living 

compatible siblings. 

Awareness of the hyperpigmentation variant 

should be noted for early detection of those 

perplexing CHS cases and study of their 

mutation analysis for better understanding 

of the disease progression and earlier 

institution of therapy. Genetic mutation 

analysis for the subtle presentation is 

pending. 

172 

REFERENCES: 



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مقارنة اشعة السونار(الموجات فوق الصوتیة)‏ علي البطن بقیاس نسبة البي اتش 

الممتد لاربعة و عشرین ساعة في الاطفال المصابین بارتجاع المریئ 

د.سوني تشونج 

: 

د.‏ نیرمین مفتاح جلال-مدرس طب الاطفال-‏ جامعة القاھرة 

استاذ طب الاطفال ‏،د.فالماي كوك:‏ استاذ الاشعة التشخیصیة ‏،د.ماري وارین:‏ استاذ 

الاشعة التشخیصیة 

– 

المملكة المتحدة 

یعد ارتجاع الطعام او السوائل من الظواھر الطبیعیة في الاطفال دون الثالثة و الذي قد یعد مرضا اذا 

ازدادت نسبتھ مسببا التھاب المریئ او اعراض اخري.‏ تھدف الدراسة الي فحص وصلة المریئ بالمعدة 

عن طریق السونار و تقییم دوره كفحص مبدئي بالمقارنة مع قیاس نسبة البي اتش الممتد لاربعة و 

عشرین ساعة في الاطفال المصابین بارتجاع المریئ عن طریق دراسة باثر رجعي.‏ 

الوسائل:‏ تم عمل سونار علي البطن لخمسین طفلا لا یشتكون باعراض ارتجاع المریئ و واحد و ثلاثین 

طفل مصابین باعراض محتم لة تم للارتجاع.‏ عمل مقارنة مع قیاس نسبة البي اتش الممتد لاربعة و 

) 

عشرین ساعة لدي نفس الاطفال.بلغ متوسط العمر ثلاثة و سبع من عشرة العمر من شھرین لاحدي 

عشر عامنس ا).‏ بة الذكور للان اث:‏ خمس ة عش ر لاربعة ت عشم ر.‏ تسجیل ح دوث الارتج اع بالس ونار و 

تكراره مع اي عیوب خلقیة في وصلة المریئ تم بالمعدة.‏ تحدید الارتجاع اذا قلت نسبة الحموضة عن 

اربعة في عشرة بالمائة من الوقت اقل من سنة و خمسة بالمائة اكشر من عام.‏ 

النتائج:تم تسجیل الارتجاع لدي خمسة عشر طفلا و بالاختبارین.‏ توافقت النتیجة سلبیا في ثمانیة حالات 

اظھ ‏.ر الس ونارط ل ارتج دياع س بس بعةی اطف ال باختب ار س لبي للب ي ات ش و اغف ل الاص ابة ف ي طف ل 

واحد.بلغت نسبة حساسیة السونار ثلاثة و تسعین بالمائة في حین بلغت خاصیة الاختبار ثلاثة و خمسین 

بالمائة مقارنة باختبار البي اتش.‏ الاستخلاص:‏ یمثل السونار فحص مبدئي مقبول في حالات ارتجاع 

المريء بقیاس مقارنة نسبة البي اتش الممتد لاربعة و عشرین ساعة لكونھ اختبار تدخلي.‏ كثرة تردد 

الارتجاع كانت من التسجیلات المفیدة لدي اجراء السونار.‏

Pattern Of Chediak Higashi Syndrome In Egyptian Children

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