Sanjad-Sakati Syndrome Research Articles

Sanjad-sakati syndrome and its association with superior mesenteric artery syndrome.

Sanjad-Sakati syndrome (SSS) is an autosomal recessive disorder found exclusively in people of Arabian origin. It was first reported in the Kingdom of Saudi Arabia in 1988 and confirmed by a definitive report in 1991. The syndrome comprises of congenital hypoparathyroidism, seizures, severe growth and developmental retardation, low IQ, and atypical facial features. Supportive treatment in the form of vitamin D and growth hormone supplementation is often offered to patients suffering from SSS. This case study focuses on the steps taken to help a patient who was found to have very unusual symptoms and was later found to have superior mesenteric artery syndrome.

Partial agenesis of corpus callosum in Sanjad–Sakati syndrome (p-ACC)

Introduction. Sanjad–Sakati syndrome (SSS) was first described in the Middle East in children of consanguineous parents [1]. It is a rare autosomal recessive disorder known also as Middle-East syndrome.

Neurological manifestations in children with Sanjad–Sakati syndrome

Background:Sanjad–Sakati syndrome (SSS), also known as hypoparathyroidism–mental retardation–dysmorphism syndrome, or HRD, is a rare disorder characterized by growth and developmental delay, and by mental retardation and dysmorphic features.Objective:The objective of this study was to clarify the clinical and neurological features of SSS.Patients:Twenty-four patients were included in the study. They were seen at two hospitals in Kuwait.Methods:This was a retrospective study of patients with SSS who attended the pediatric endocrinology, genetic, and neurology clinics in the Aladan and Alfarawanya hospitals in Kuwait from September 2007 to September 2012. Clinical and radiological data were obtained from each patient’s medical records.Results:All 24 patients had the characteristic dysmorphic features and laboratory findings of SSS. Consanguinity was reported in 75% of parents. Neurological manifestations in the form of microcephaly, developmental delay, mental retardation, and seizures were reported in all patients. Computerized tomography scans and/or magnetic resonance imaging showed evidence of intracranial calcifications in 29.2% of patients. Two patients showed a thin corpus callosum, and one patient showed intraventricular hemorrhaging.Conclusion:Patients with SSS display a variety of dysmorphic features and neurological manifestations, including microcephaly, mental retardation, intracranial calcification, and epilepsy.

Sanjad-sakati syndrome dental management: a case report.

Sanjad-Sakati syndrome (SSS) is a rare genetic disorder with autosomal recessive pattern of inheritance characterized by hypoparathyroidism, sever growth failure, mental retardation, susceptibility to chest infection, and dentofacial anomalies. A child with SSS was referred to the dental departmentseeking dental help for sever dental caries which was attributed to his dietary habits and quality of dental tissues. Full restorative rehabilitation was done under general anesthesia. Two years later, the child presented with recurrent caries affecting uncrowned teeth. High carries recurrence rate was blamed for the nutritional habits endorsed by the parents. Only steel crowned teeth survived such hostile oral environment which suggested shifting of treatment strategy towards full coverage restorations instead of classical cavity preparations and fillings during a second attempt for dental treatment under general anesthesia and for the dental treatment of two cousins of the same child. The author recommends effective health education for parents including the nature of their child's genetic disorder, nutritional needs, and dental health education to improve the life style of such children.

Sanjad Sakati syndrome: a case series from Jordan

Sanjad Sakati syndrome is a rare autosomal recessive disorder that has been described in Arabs. We report 8 patients from 7 Jordanian families, 6 of whom underwent genetic testing and were found to have a 12 bp (155-166 del) deletion within the tubulin-specific chaperone E (TBCE gene) in exon 3 at 1q42-43. All patients had severe growth retardation, distinct phenotypic features and hypoparathyroidism. Parental consanguinity was recorded in all families. This is the first genetically proven case series of Sanjad Sakati syndrome in Jordan.

Recombinant Parathyroid Hormone Therapy for Severe Neonatal Hypoparathyroidism

Hypoparathyroidism-retardation-dysmorphism (HRD) syndrome (OMIM 241410), also known as SanjadSakati syndrome, is a rare autosomal recessive disorder characterized by hypoparathyroidism, growth failure, developmental delay, and characteristic facies. We describe the effective short-term use (tapered over 12 days) of recombinant parathyroid hormone (PTH) (teriparatide) in an unusual genetic condition characterized by hypoparathyroidism. Standard treatment for hypoparathyroidism involves oral vitamin D analogues and calcium, often in large doses to achieve sufficient intestinal calcium transport to overcome the hypercalciuria and concomitant malabsorption. 1 Despite its known physiological benefits, 2 recombinant PTH is not usually considered in the treatment algorithm for hypoparathyroidism in the pediatric population. Case Report Approval for this case report was obtained from the Human Research Ethics Committee of The Children’s Hospital at Westmead. Informed consent was obtained from the family. A female infant was born to first-cousin Iraqi parents at 31 weeks gestation, after an antenatal course that included oligohydramnios and fetal growth restriction. The parents had previously experienced 2 first-trimester miscarriages and fetal death at 30 weeks, and the current pregnancy was conceived after in vitro fertilization. She had a birth weight of 1190 g (SDS, 1.02), length of 36.5 cm (SDS, 1.77), and head circumference of 25.4 cm (SDS, 1.61). Dysmorphic features included deep-set eyes, large ears with hypoplastic posterior helices, and a thin nose (Figure 1). The newborn period was complicated by respiratory distress syndrome, treated with surfactant, mechanical ventilation, and continuous positive airway pressure. Significant feeding intolerance and vomiting were present from the first week of life. Upper gastrointestinal studies showed gastric hypomotility and delayed passage into the duodenum with no mechanical obstruction. Transpyloric tube feeding was started at 4 weeks after birth. Fat malabsorption was confirmed by fecal fat analysis and low serum vitamin A and E levels. Results of a sweat test were normal. Pancreatic enzyme replacement and fat-soluble

Sanjad-Sakati Syndrome in Omani children.

Sanjad Sakati Syndrome is an Autosomal Recessive disorder found exclusively in people of Arabian origin. It was first reported from the Kingdom of Saudi Arabia in 1988. This is a report of a family with this rare disease in Oman. The syndrome comprises of congenital hypoparathyroidism, severe growth retardation, low IQ and typical facial features. Supportive treatment in the form of vitamin D and growth hormone is often offered to these children.

Sanjad — Sakati syndrome in a neonate

Congenital hypoparathyroidism, growth retardation and dysmorphism is a rare autosomal recessive syndrome among Arab population commonly known as Sanjad-Sakati syndrome(SSS).Several metabolic and septic complications are known to manifest in the neonatal age. We describe the first report of morbid pathological fractures affecting a neonate with SSS.

Visceral myopathy causing chronic intestinal pseudoobstruction and intestinal failure in a child with Sanjad-Sakati syndrome

Sanjad-Sakati syndrome is a rare autosomal recessive disorder mainly occurring in the Arab Peninsula. This condition is associated with metabolic and septic complications starting in the neonatal period. Chronic intestinal pseudoobstruction owing to visceral myopathy is a rare disabling condition. We report a rare concurrence of Sanjad-Sakati syndrome and chronic intestinal pseudoobstruction in a Saudi child complicated by intestinal failure, sepsis, and early mortality.

The Otolaryngologic Features of Sanjad-Sakati Syndrome

Sanjad-Sakati syndrome (SSS) is a rare autosomal recessive disorder seen in children of Middle Eastern descent, predominantly of consanguineous parents. This disorder has been mapped to the long arm of chromosome 1 (1q42-q43) and is caused by mutations in the TBCE gene (OMIM 241410), encoding a tubulin-specific chaperone E. 1 .

Sanjad-Sakati syndrome/Kenny-Caffey syndrome type 1: a study of 21 cases in Kuwait

We studied 21 patients with Sanjad-Sakati syndrome (SSS) from 16 families. Parental consanguinity was recorded in 2 families (12.5%). All patients had severe intrauterine growth retardation, short stature, small hands and feet, blue sclera, deep-set eyes, microcephaly, persistent hypocalcaemia and hypoparathyroidism. Medullary stenosis was detected in 2 patients. Cytogenetic and fluorescent in situ hybridization studies were normal. All affected persons had homozygous deletion of 12 bp (155-166del) in exon 3 of the TBCE gene. All of the parents were heterozygous carriers of this mutation. The high frequency of SSS and low frequency of consanguineous marriages in this study may reflect a high rate of heterozygous carriers.

Ophthalmic features of hypoparathyroidism-retardation-dysmorphism

Hypoparathyroidism-retardation-dysmorphism (HRD; Sanjad-Sakati Syndrome; Online Mendelian Inheritance in Man [OMIM] #241410) is a rare recessive syndrome predominantly seen on the Arabian Peninsula and characterized by congenital hypoparathyroidism, intrauterine growth retardation, mental retardation, seizures, and a typical facial dysmorphism (prominent forehead, deep-set eyes, and abnormal external ears).(1,2) To date, the same homozygous deletion in TBCE (155-166del) has been reported in all Saudi Arabian patients with HRD(1) as well as in all Saudi Arabian patients with Kenny-Caffey syndrome (OMIM #244460),(1) a syndrome with a phenotype that resembles that of HRD but is characterized by the presence of normal intelligence, late closure of the anterior fontanelle, macrocephaly, and postnatal (rather than prenatal) growth retardation.(1,3) Nanophthalmos and corneal opacity have been documented in Kenny-Caffey syndrome patients,(4) but ocular disease has not been well-described in HRD. We describe the ocular features of four Saudi Arabian HRD children referred to our institution for ocular complaints noted by their parents.

Hypothyroidism‐retardation‐dysmorphism (HRD): Is there a new variant not caused by a TBCE mutation?

To the Editor:Courtensetal.[2006]publishedaClinicalReportina March issue describing a girl from Morocco withhypothyroidism-retardation-dysmorphism (HRD):a new variant not caused by a TBCE mutation.According to this report, the patient fulfilled thecriteriafor thediagnosis of Sanjad–Sakati syndrome(SSS;OMIM:241410).WethinkthatthispatientisnotSSS for the following reasons:PreviouslyreportedSSSpatientshadbothprenatalandpostnatalgrowthretardationsandmicrocephalyas cardinal features [Sanjad et al., 1988, 1991;RichardsonandKirk,1990,1991;KalamandHafeez,1992; Marsden et al., 1994; Hershkovitz et al., 1995;Soliman et al., 1996; Al-Gazali and Dawodu, 1997;Al-Malik, 2004; Al Tawil et al., 2005; Naguib et al.,unpublished data]. At birth, the measurements ofCourtensetal. patientwereall withinnormalrange.The authors claimed that their patient had prenatalgrowthretardation(TableIofthepublishedreport),asherbirthlengthwas48cm.Accordingtonormsoflength [Jones, 1997] the 48 cm lies between the 10thandthe25thcentile,whichisnotgrowthretardation.At the age 4½ years, the proposita had normal bodymeasurementswithrelativemacrocephaly(weightat25th centile, height at 10th centile, and OFC at 97thcentile).ThisagaindoesnotfitwiththediagnosisofSSS.Most of the characteristic facial dysmorphism ofSSS,suchasexternalearanomalies,lowsetears,anddeep set eyes, are missing in the patient’s photo.Moreover, normocephaly/macrocephaly is afeature of Kenny–Caffey syndrome type 2 ratherthan SSS.The proposita is the only affected member in herfamily. This does not justify the autosomal recessivemodeofinheritanceeveninthepresenceofparentalconsanguinity which is common among Arabs(30%–54%) [AL-Awadi et al., 1985].Thus, we have a patient with normal bodymeasurements, minor dysmorphic facial features,normo/macrocephaly, psychomotor retardation,seizures, hypoparathyroidism, hypocalcemia, andpossibility of immune impairment, despite normalhumoral and cellular immunological testing. ThepatientwithsuchcriteriadoesnotfitthediagnosisofSSS, and so TBCE gene mutations are not expected.ThesefeaturesarecommoninCHARGEassociation,22q11 deletion, and Kenny-Caffey syndromes.Reevaluation of the proposita is highly suggestedbefore reaching to any conclusion.REFERENCES

Anesthesia management for the child with Sanjad–Sakati syndrome

Sanjad-Sakati syndrome (SSS) is a rare genetic disorder characterized by congenital hypoparathyroidism, hypocalcemia and hyperphosphatemia, seizures, severe intrauterine and postnatal growth failure, dwarfism, mental retardation, dysmorphic features including retromicrognathia and abnormal dentition and increased susceptibility to infection. It is mainly confined to children in the Middle-East countries. We report the anesthesia management of a 12-year-old boy with SSS for dental treatment, and discuss the anesthesia implications of this disorder.

Hypoparathyroidism‐retardation‐dysmorphism syndrome in a girl: A new variant not caused by a TBCE mutation—clinical report and review

Hypoparathyroidism-retardation-dysmorphism (HRD) or Sanjad-Sakati syndrome (SSS) (OMIM 241410) is a rare autosomal recessive (AR) inherited condition, characterized by congenital hypoparathyroidism (hypoPTH), retardation, seizures, and a typical facial dysmorphism, consisting of prominent forehead, deep-set eyes, and abnormal external ears. This disorder has been mapped to the long arm of chromosome 1 (1q42-q43) and mutations in the gene coding for tubulin-specific chaperone E (TBCE) have been identified as the cause of the disease. Mutations in the same gene were also reported in patients with AR Kenny-Caffey syndrome (KCS). We report on a 41/2-year-old girl with congenital hypoPTH, seizures, developmental delay, and a facial dysmorphism, compatible with HRD syndrome. Mutation analyses revealed no mutations in the TBCE gene. In addition, normal TBCE protein and alpha-tubulin immunostaining were observed in a lymphoblastoid line derived from the patient, excluding the TBCE gene as the causative gene of the syndrome in this patient. A de novo microduplication of probe RP11-262I1 on 4q35 in the proposita was detected by microarray analyses, but this could not be confirmed by additional studies. We review and discuss the clinical findings of our case and those of the other reported cases with SSS and AR KCS. We conclude that a second gene locus for this disorder seems probable and that 4q35 needs further evaluation as a candidate region.

Ophthalmic Manifestations of Sanjad-Sakati Syndrome

Background: Sanjad-Sakati syndrome (SSS) is a rare disorder characterized by hypoparathyroidism, growth and developmental delay, and dysmorphism. The purpose of this report is to describe the ophthalmic manifestations of Sanjad-Sakati syndrome (SSS; hypoparathyroidism-mental retardation-dysmorphism syndrome, HRD) (OMIM 241410). Patients: We included a total of 17 patients who were seen at two hospitals in Riyadh. Methods: Each patient underwent a complete ophthalmologic evaluation including visual acuity assessment, orthoptic workup, slit-lamp biomicroscopy, intraocular pressure measurement, cycloplegic retinoscopy, funduscopy, corneal diameter, and axial length measurement. Results: All 17 (100%) of the patients had normal visual acuity. All patients had microphthalmia with normal intraocular pressure. Eight (47%) of the patients had esotropia and four (23%) had exotropia. Ophthalmoscopy revealed tortuous retinal blood vessels in all patients. Hyperopic astigmatism was present in 16 (94%) patients. Conclusion: Patients with SSS display a variety of ocular findings including errors of refraction, strabismus, and retinal vascular tortuousity.

Hypoparathyroidism–retardation–dysmorphism (HRD) syndrome in triplets

We report female triplets with the clinical and biochemical manifestations of hypoparatyroidism-retardation-dysmorphism (HRD) syndrome also known as Sanjad-Sakati syndrome. They were born at 35 weeks gestation after assisted pregnancy (in vitro fertilization). The parents are first degree cousins from Saudi Arabia.

Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome.

The syndrome of congenital hypoparathyroidism, mental retardation, facial dysmorphism and extreme growth failure (HRD or Sanjad-Sakati syndrome; OMIM 241410) is an autosomal recessive disorder reported almost exclusively in Middle Eastern populations. A similar syndrome with the additional features of osteosclerosis and recurrent bacterial infections has been classified as autosomal recessive Kenny-Caffey syndrome (AR-KCS; OMIM 244460). Both traits have previously been mapped to chromosome 1q43-44 (refs 5,6) and, despite the observed clinical variability, share an ancestral haplotype, suggesting a common founder mutation. We describe refinement of the critical region to an interval of roughly 230 kb and identification of deletion and truncation mutations of TBCE in affected individuals. The gene TBCE encodes one of several chaperone proteins required for the proper folding of alpha-tubulin subunits and the formation of alpha-beta-tubulin heterodimers. Analysis of diseased fibroblasts and lymphoblastoid cells showed lower microtubule density at the microtubule-organizing center (MTOC) and perturbed microtubule polarity in diseased cells. Immunofluorescence and ultrastructural studies showed disturbances in subcellular organelles that require microtubules for membrane trafficking, such as the Golgi and late endosomal compartments. These findings demonstrate that HRD and AR-KCS are chaperone diseases caused by a genetic defect in the tubulin assembly pathway, and establish a potential connection between tubulin physiology and the development of the parathyroid.

Sanjad-Sakati and autosomal recessive Kenny-Caffey syndromes are allelic: evidence for an ancestral founder mutation and locus refinement.

The Sanjad-Sakati syndrome (SSS; MIM241410), an autosomal recessive trait characterized by congenital hypoparathyroidism, growth and mental retardation, seizures, and a characteristic physiognomy, was recently linked to chromosome area 1q42-q43. SSS resembles the autosomal recessive form of Kenny-Caffey syndrome (KCS; MIM244460), with similar manifestations but lacking osteosclerosis. Since KCS was recently linked to the region 1q42-q43, the possibility that this disorder is allelic with SSS was considered. Eight Sanjad-Sakati families from Saudi Arabia were genotyped with polymorphic short tandem repeat markers from the SSS/KCS critical region. A maximum multipoint LOD score of 14.32 was obtained at marker D1S2649, confirming linkage of SSS to the same region as autosomal recessive KCS. Haplotype analysis refined the critical region to 2.6 cM and identified a rare haplotype present in all the SSS disease alleles, indicative of a common founder. In addition to the assignment of the Saudi SSS and Kuwaiti KCS syndromes to overlapping genetic intervals, comparison of the haplotypes unexpectedly demonstrated that the diseases shared an identical haplotype. This finding, combined with the clinical similarity between the two syndromes, suggests that the two conditions are not only allelic but are also caused by the same ancestral mutation.

Linkage Mapping of the Kenny-Caffey Syndrome and Evidence for Allelism with the Sanjad-Sakati Syndrome

Linkage Mapping of the Kenny-Caffey Syndrome and Evidence for Allelism with the Sanjad-Sakati Syndrome