MIDDLE EAST SYNDROME

YASSIN M ALSALEH

قال تعالى:�ِذ�ي ) ُه�َو� ال

�ْم# ِف�ي ُك ��َص�َو'ُر ُي �#َف �ْي � ُك َح�اِم ُر#

� اَأل � �َّال َه� ِإ �ـ �ل � ِإ اء َّال ��َش ُي

�#ع�ُز�ُيُز ُه�َو� ال) �#َح�ِك�ْيْم ال

سَوُرة آل 6عمران :

He is Who shapes you in the wombs as He pleases. There is no

god but He, the Exalted in Might, the

Wise

SSSSANJAD SAKATI

SUNDROME

HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM

SYNDROME

HRD

CASE SCENARIO

2 weeks old girl presented with generalized tonic clonic convulsion.

product of FT,NSVD, B.W:1.8kg . Father is deaf, consangoius marriage. On exam: Wt and length : <3ed . Dysmorphic . Deep seated eye. CVS: S1+S2+ SM. Lab: calcium 1.5 posphorus: 3.5 PTH:

undetectable

Impression: Hypoparathyrodisim

DDx: SSS )HRD(. HDR . DiGeorge . Kenny–Caffey syndrome

CASE SCENARIO

INTRODUCTION

first reported in 1988 . its inheritance and configuration was

confirmed in 1991. It has been reported almost exclusively

in the Middle Eastern population. characterized by congenital

hypoparathyroidism, retarded growth, mental retardation and a characteristic physiognomy .S A Sanjad, N A Sakati, Y K Abu-Osba, R Kaddoura, R D G Milner. A new

syndrome of congenital hypoparathyroidism, severe growth failure, and dysmorphic features. Archives ofDisease in Childhood 1991; 66: 193-196

The presenting complaint in most of the patients was hypocalcaemic with generalised convulsions, usually detected in the first few days or weeks of life.

the age at diagnosis of ranged from 1st week of life to 12 years.

some authors consider it a variant of Kenny–Caffey syndrome type 1.

M=F

INTRODUCTION

J. Albaramki, K. Akl, A. Al- Muhtaseb, M. Al-Shboul, T. Mahmoud, M. El-Khateeb and H. Hamamy.Sanjad Sakati syndrome: a case series from Jordan : Eastern Mediterranean Health Journal, vol. Vol. 18 No. 5 • 2012

INCEDINCE

found exclusively in people of Arabian origin.

It is not uncommon in the Gulf area, especially Saudi Arabia.

the incidence in Saudi Arabia varies from 1:40 000 to 1:100 000 live births.

In Kuwait the incidence is 7–8 per 100 000 live births.

The parents of most of the cases being consanguineous.

K.K. Naguib, S.A. Gouda, A. Elshafey, F. Mohammed, L. Bastaki, A.S. Azab and S.A. Alawadi. Sanjad–Sakati syndrome/Kenny– Caffey syndrome type 1: a study of 21 cases in Kuwait .Eastern Mediterranean Health Journal, Vol. 15, No. 2, 2009

3

624

????

22

8

India 1

4

autosomal recessive disorder. due to mutations in the tubulin-specific

chaperone E )TBCE( gene in chromosomal area 1q42–q43.

The gene TBCE encodes a protein that participates in beta-tubulin folding.

Tubulin is needed for many essential life processes, including cell division and proper organelle positioning in the cell.

GENETIC

Ruti Parvari,a George A. Diaz ,b Eli Hershkovitz . Parathyroid Development and the Role of Tubulin Chaperone E. Horm Res 2007;67:12–21.

One female child from Belgium not caused by a TBCE mutation.

Diagnosis is mainly clinical.

GENETIC

Winnie Courtens, Wim Wuyts,Martin Poot, Karoly Szuhai, Jan Wauters, Edwin Reyniers, Marc Eleveld, George Diaz, Markus M. No¨then, and Ruti Parvari. Clinical Report Hypoparathyroidism -Retardation-Dysmorphism Syndrome in a Girl: A New Variant Not Caused by a TBCE Mutation—Clinical Report and Review: American Journal of Medical Genetics 140A:611–617 )2006(.

CLINICAL PRESENTATION

IUGR. mental retardation. short stature. microcephaly. small hands and feet. beaked nose. depressed nasal

bridge. external ear

anomalies.

deep-set eyes. Thin upper lip long philtrum micrognathia, enamel hypoplasia repeated infections. persistent

hypocalcaemia and hypoparathyroidism.Yaser El-Tal MD, Sameer Marji MD, JMCC, Hussein Shawaqfeh MD, JMCC,

Khalid Okour MD, JMCC . SANJAD – SAKATI SYNDROME: A REPORT OF TWO CASES . JOURNAL OF THE ROYAL MEDICAL SERVICES Vol. 15 No. 3 December 2008

Recurent chest infection is leading cause of death.

Also they have high tendency to ear infection.

Functional Hyposplenism And impaired polymorphonuclear cell functions could be the cause .

Reduced numbers of T-cell subsets were found.

CLINICAL PRESENTATION

Hershkovitz E, Rozin I, Limony Y. Hypoparathyroidism, retardation, and dysmorphism syndrome: impaired early growth and increased susceptibility to severe infections due to hyposplenism and impaired polymorphonuclear cell functions. Pediatric research. 2007 Oct;62)4(:505-9.

blue sclera. high arched palate, Nystagmus. optic nerve

coloboma. Cryptorchidism. medullary stenosis

of long bones.

intracranial calcifications

Cataract. central

hypoventilation obstructive sleep Partial Agenesis of

Corpus Callosum

CLINICAL PRESENTATION others

Eli Hershkovitz, Reli Hershkovitz, Lora Hertzug, Rafael Gorodischer, Moshe Mazor and Ruti Parvari. Prenatal diagnosis of hypoparathyroidism retardation and dysmorphism (HRD) syndrome Prenat Diagn 2000; 20: 475±477.

Kenny–Caffeysyndrome, type 2

Kenny–Caffeysyndrome, type 1

Sanjad–Sakatisyndromea

Macrocephaly Microcephaly/macro

Microcephaly Craniofacial

Normal mentality

Mental retardation/normal mentality

)mildto moderate

Mental

thickened cortex and, medullary stenosis osteosclerosis

medullary stenosis oftubular bones; osteosclerosis

Micropenis,cryptorchidism,

other

Transient hypocalcemia, transienthypophosphataemia

Hypocalcaemia lowparathyroid hormone;low to low-normalmagnesium

Hypocalcaemia; lowparathyroid hormone;hyperphosphataemia

lab

Cell mediated defect

Cell mediated defect

normal immunity

FAM111A TCBE mutation TCBE mutation molecular

AD/Xlinked AR AR Inheritance

INVESTIGATION

Calcium ,Phosphorus, magnesium. PTH. TBCE gene study. Renal US. Bone age. Brain CT/MRI.

limited to palliative therapy. Calcium and one alpha calcidol or

1,25)OH(2 D3 )calcitriol(. Low phosphorus formula. treating intercurrent infections. Attempts to use growth hormone in

some of the cases proved unsuccessful.

TREATMENT

Khalil Al Tawil,* Adnan Shataiwi, Angham Mutair, Wafa Eyaid, and Saif Al Saif. Hypoparathyroidism–Retardation–Dysmorphism (HRD) Syndrome in Triplets : American Journal of Medical Genetics 135A:200–201 )2005(

PREVENTION

daily antibiotic prophylaxis against pneumococcal infections + vaccination

prevention could be achieved through preimplantation genetic diagnosis )PGD( and carrier detection.

Amniocentesis also can be done.

Ali Hellani*, Aida Aqueel, Kamal Jaroudi, Pinar Ozand and Serdar Coskun. Pregnancy after preimplantation genetic diagnosis for Sanjad–Sakati syndrome : PRENATAL DIAGNOSIS 2004; 24: 302–306.

complication

Nephrocalcinosis. Nephrolithiasis. renal insufficiency. recurrent infections.

PROGNOSIS

recurrent infections, is the cause of death in at least 27%.

rare cases have survived up to the age of 18 years.

KFMC DATA BASEAbduelelah almadhany

Alwaleed Algoud

Adary Alotibi

Bader Alotibi

Meshal Alotibi

Waad Aldajani

M M F M M F SEX

1y5m 4y 7y7m 8y9m 14 year 19 year AGE

1-alpha , Hydrochlorothiazide.

1-alpha, Mgso4, ca, Caco3,Hydrochlorothiazide.

1-alpha, ca

1-alpha, CaCO3, Hydrochlorothiazide.

1-alpha, Mgso4, Hydrochlorothiazide.

1-alpha, Mgso4, Hydrochlorothiazide, thyroxine,

TREATMENT

Y Y NO Y Y Y nephrocalcinosis

Y Y NO Y Y Y hypercacuria

Y ???? ???? Y Y ???? TBCE mutation

Sngle kideny, malrotation,GERD,

undescended testicle,micropenis, VSD

Recurrent ear infection

undescended testicle

trachyostomy

Hypothyroidism, sleep apnea, central hypoven , trachyostomy, DVT, malrotation

OTHER

REFERANCES

K.K. Naguib, S.A. Gouda, A. Elshafey, F. Mohammed, L. Bastaki, A.S. Azab and S.A. Alawadi. Sanjad–Sakati syndrome/Kenny– Caffey syndrome type 1: a study of 21 cases in Kuwait :Eastern Mediterranean Health Journal, Vol. 15, No. 2, 2009

J. Albaramki, K. Akl, A. Al- Muhtaseb, M. Al-Shboul, T. Mahmoud, M. El-Khateeb and H. Hamamy.Sanjad Sakati syndrome: a case series from Jordan : Eastern Mediterranean Health Journal, vol. Vol. 18 No. 5 • 2012

Yaser El-Tal MD, Sameer Marji MD, JMCC, Hussein Shawaqfeh MD, JMCC, Khalid Okour MD, JMCC . SANJAD – SAKATI SYNDROME: A REPORT OF TWO CASES . JOURNAL OF THE ROYAL MEDICAL SERVICES Vol. 15 No. 3 December 2008

Ali Hellani, Aida Aqueel, Kamal Jaroudi, Pinar Ozand and Serdar Coskun. Pregnancy after preimplantation genetic diagnosis for Sanjad–Sakati syndrome : PRENATAL DIAGNOSIS 2004; 24: 302–306.

REFERANCES

Eli Hershkovitz, Reli Hershkovitz, Lora Hertzug, Rafael Gorodischer, Moshe Mazor and Ruti Parvari. Prenatal diagnosis of hypoparathyroidism retardation and dysmorphism (HRD) syndrome Prenat Diagn 2000; 20: 475±477.

Khalil Al Tawil,* Adnan Shataiwi, Angham Mutair, Wafa Eyaid, and Saif Al Saif. Hypoparathyroidism–Retardation–Dysmorphism (HRD) Syndrome in Triplets : American Journal of Medical Genetics 135A:200–201 )2005(

REFERANCES

Winnie Courtens, Wim Wuyts,Martin Poot, Karoly Szuhai, Jan Wauters, Edwin Reyniers, Marc Eleveld, George Diaz, Markus M. No¨then, and Ruti Parvari. Clinical Report Hypoparathyroidism-Retardation-Dysmorphism Syndrome in a Girl: A New Variant Not Caused by a TBCE Mutation—Clinical Report and Review: American Journal of Medical Genetics 140A:611–617 )2006(.

REFERANCES

Ruti Parvari,a George A. Diaz ,b Eli Hershkovitz . Parathyroid Development and the Role of Tubulin Chaperone E. Horm Res 2007;67:12–21.

S A Sanjad, N A Sakati, Y K Abu-Osba, R Kaddoura, R D G Milner. A new syndrome of congenital hypoparathyroidism, severe growth failure, and dysmorphic features. Archives ofDisease in Childhood 1991; 66: 193-196

REFERANCES

R J Richardson, J M W Kirk. Short stature, mental retardation, and hypoparathyroidism: a new syndrome. Archives ofDisease in Childhood 1990; 65: 1113-1117.

Bushra Rafique and Saif Al-Yaarubi. Sanjad-Sakati Syndrome in Omani children. doi:10.5001/omj.2010.63.

Naif ALGhasab, A. Bruce Janati, Aslam KhanPartial Agenesis of Corpus Callosum in Sanjad-Sakati Syndrome (p-ACC). Can J Neurol Sci. 2012; 39: 833-834

REFERANCES

Hershkovitz E, Rozin I, Limony Y. Hypoparathyroidism, retardation, and dysmorphism syndrome: impaired early growth and increased susceptibility to severe infections due to hyposplenism and impaired polymorphonuclear cell functions. Pediatric research. 2007 Oct;62)4(:505-9.

kalenahlli J, Halasahalli C. Hypoparathyroidism-retardation-dysmorphism syndrome. Indian J Hum Genet. 2013 Jul-Sep; 19)3(: 363–365.

REFERANCES

Ahmed Farag Elhassanien,Hesham Abdel-Aziz Alghaiaty. Neurological manifestations in children with Sanjad–Sakati syndrome,International Journal of General Medicine may 2013.

Wiam A. Arabi, Areej A. Basheer, Mohamed A. Abdullah .Sanjad-Sakati Syndrome in Sudanese children SUDANESE JOURNAL OF PAEDIATRICS Vol. 11, No. 1. 2011.

REFERANCES