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

Abstract

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.

Sanjad Sakati syndrome: a case series from Jordan

“…Homozygous deletion of 12 bp in exon 3 of the TBCE gene was confirmed to be the cause of this syndrome (OMIM 241410) [4]. This mutation has been described in Arabs with Sanjad Sakati syndrome, but in 2006 Courten et al described a 4.5-year-old girl with the syndrome who did not have a mutation in the TBCE gene and found another possible gene locus [10].…”

The Otolaryngologic Features of Sanjad-Sakati Syndrome

“…The syndrome is also associated with a growth hormone deficiency. 1 Although patients with SSS are prone to recurrent pneumonia and other bacterial infections, assessment of immune function shows a normal range. 9 Endocrine disorders, craniofacial anomalies, dwarfism, and hypoxia can cause difficulties in airway management, as seen in our patient.…”

Sanjad-Sakati syndrome in a Tunisian child

“…The TBCE gene encodes for a tubulin-specific chaperone E protein required for the proper folding of alphatubulin subunits and the formation of alpha-beta-tubulin heterodimers [7][8][9]. SSS is not uncommon in Middle Eastern populations and has a high prevalence among Arabs [1,3,8,[10][11][12][13][14][15][16]. Interestingly, all affected patients of Arab origin have shown homozygosity for a 12-bp (155-166del) deletion in exon 3 of the TBCE gene.…”