Abdel-Al et al. (1989) reported a Kuwaiti girl suffering from Kenny-Caffey syndrome and idiopathic hypoparathyrodism at Al-Kabeer Hospital in Kuwait. The girl was born with a birth weight of 2.7kg after an uneventful pregnancy; her parents are first cousins with 4 other normal children. The patients' mother had two other pregnancies before her, the boy passed away at birth and the girl passed away at the age of 3monts after suffering respiratory difficulties and hypocalcemia. The subject and her family underwent radiologic examinations which showed no evidence of pseudo-hypoparathyroidism or hypoparathyroidism for the subject and was normal for all family members. Since the patient's sister passed away at the age of 3months due to hypocalcemia without previous family history, Abdel-Al et al. (1989) suggested that the inheritance of this syndrome is autosomal recessive.
Khan et al. (1997) reported 16 cases of Kenny-Caffey syndrome (KCS) at Al-Jahra in Kuwait, where more than 80% of the Bedouin ancestry were consanguineous. Five of the cases passed away at early infancy due to hypocalcemic seizures, while 11 cases were suffering from KCS. Case 1 represented a girl born after an uneventful antenatal period by breech presentation with birth weight of 2000g born to a healthy consanguineous Bedouin parents. The patients' family consisted of 11 children where she was the seventh child, two of the children passed away in infancy due to hypocalcemic convulsions, two younger sibs were likewise affected, and the six remaining children were found to be healthy. Case 2 represented a girl born from a breech presentation with birth weight of 2000g, she was diagnosed with intrauterine growth retardation at birth since the mother did not attend antenatal follow up. Hematological survey indicated the presence of an unexplained anemia. Case 3 represented a boy who was born normally with birth weight of 1800g and was found to suffer from intrauterine growth retardation with typical KCS features. Six other unrelated families were examined and the results showed the presence of classical craniofacial findings and hypocalcemia. Merely two children were found to be asymptomatic. Classic radiological findings of KCS, delayed mental and motor development were found in all children. Studying all these cases, Khan et al. (1997) confirmed the autosomal recessive inheritance of KCS.
Sabry et al. (1998) reported four sibs with Kenny-Caffey syndrome in a consanguineous Bedouin family in Kuwait. The parents were healthy Bedouin first cousins who had five healthy daughters, two healthy sons, an affected son (case 2), an affected daughter (case 1), two affected daughters who passed away (cases 3 and 4), and a stillborn boy. Case 1 represented a girl born with a birth weight of 2250g, she underwent several medical tests including skeletal, immunological and conventional cytogenetic testing. The cytogenetic test was unsuccessful in distinguishing any abnormality in the chromosome constitution of the two Bedouin sibs (case 1 and 2) or their parents. Therefore, fluorescence in situ hybridization (FISH) was employed to blood lymphocyte metaphase which was collected from the affected subjects, their parents and form normal control samples. Probe D22S75 which is specific to DiGeorge critical region (DGCR) on chromosome 22q11.2 was employed with chromosome 22q13.3 control probe D22S39. 20 metaphases were investigated for every subject. The same probe identified a signal on only one of the chromosome 22 pair from the affected patients and their mother, therefore suggesting the presence of a maternally inherited 22q11.2 hemizygous microdeletion in the sibs suffering from Kenny-Caffey syndrome. Case 2 represented a boy who was born by Lower Segment Cesarian Section (LSCS) due to fetal distress with a birth weight of 2500g. The patient suffered from haploinsufficiency at DGCR (22q11.2) which was revealed during the FISH test. Case 3 represented a female born at 38 weeks gestation with a birth weight of 2210g, she passed away at the age of 55 days due to an apneic attack. Case 4 represented a female with a birth weight of 2500g who passed away at the age of 18 days due to recurrent apneic episodes. The identification of the maternally inherited hemizygous microdeletion in the juxatacentromeric region of the long arm chromosome 22 (22q11.2) in the Bedouin patients led Sabry et al. (1998) to suggest that Kenny-Caffey syndrome could be a new member of CATCH 22 family.
Later, Sabry et al. (1999) demonstrated two unrelated girls from Bedouin families suffering from the same features representing Kenny-Caffey syndrome (KCS). Both patients demonstrated microcephaly and psychomotor retardation, hence differentiating this phenotype form the classical KCS with only macrocephaly with delayed closure of the fontanel and normal intelligence. Case 1 represented a proposita born to a first-cousin Bedouin parents with a birth weight of 2250g. The patients' parents had six phenotypically normal children and a history of one early abortion, also it was reported that a deceased male maternal first cousin suffered from similar disease profile to case 1. Fluorescence in situ hybridization (FISH) analysis did not confirm the presence of a 22q11.2 microdeletion. Case 2 represented a proposita born by a Cesarean section after 32 weeks gestation owing to placenta previa and had a birth weight of 1500g. The patients' parents were healthy first cousins with three phenotypically healthy children. FISH) analysis did not confirm the presence of a 22q11.2 hemizygosity. Sabry et al. (1999) suggested that these two cases denoted an Arab variant of KCS with characteristic microcephaly and psychomotor retardation.
Parvari et al. (2002) demonstrated homozygosity for a 12-bp deletion in the second coding exon of the TBCE gene in more than 50 Middle Eastern individuals with hypoparathyroidism-retardation-dysmorphism syndrome. However, the phenotype in 8 pedigrees with 13 affected individuals was that of autosomal recessive Kenny-Caffey syndrome, differing from the phenotype in HRD families (17 Saudi pedigrees, 27 affected individuals; 9 Palestinian pedigrees, 25 affected individuals) owing to the additional presence of medullary stenosis of the long bones, calvarial osteosclerosis, and susceptibility to bacterial infection. The presence of patchy osteosclerosis in the long bones of some Saudi subjects with HRD and deaths secondary to sepsis in some Palestinian Bedouin individuals with HRD suggested variable expression of these phenotypic features in a pedigree-specific fashion.