Alternative titles; symbols
ORPHA: 2333, 93324; DO: 0080722;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q42.3 | Kenny-Caffey syndrome, type 1 | 244460 | Autosomal recessive | 3 | TBCE | 604934 |
A number sign (#) is used with this entry because Kenny-Caffey syndrome type 1 (KCS1) is caused by homozygous or compound heterozygous mutation in the TBCE gene (604934) on chromosome 1q42.
Biallelic mutation in the TBCE gene can also cause Sanjad-Sakati syndrome (HRDS; 241410) and progressive encephalopathy with amyotrophy and optic atrophy (PEAMO; 617207).
Kenny-Caffey syndrome type 1 (KCS1) is an autosomal recessive bone dysplasia characterized by short stature, osteosclerosis with medullary stenosis of the long bones, episodic hypocalcemia, and ocular abnormalities. Patients usually exhibit microcephaly, normal closure of the fontanels, and psychomotor delay (summary by Diaz et al., 1998).
Also see Kenny-Caffey syndrome type 2 (KCS2; 127000), an autosomal dominant and more common form of the disorder (Franceschini et al., 1992).
Franceschini et al. (1992) suggested autosomal recessive inheritance of Kenny-Caffey syndrome in female and male sibs, born of normal consanguineous parents. The sister died at 10 days of age with generalized hypertonic seizures associated with hypocalcemia. The later-born brother had neonatal hypoparathyroidism; at 1 year of age, he was short but intelligent. Both infants showed characteristic cortical thickening and medullary stenosis. Franceschini et al. (1992) noted that recessive inheritance was also suggested by the parental consanguinity in a family with a single affected child (Bergada et al., 1988) and by the family with 2 affected infants with the same normal father and different normal mothers who were sisters (Sarria et al., 1980).
Khan et al. (1997) reported 16 affected children in 6 unrelated sibships, born to healthy, consanguineous parents of Bedouin ancestry. They were able to assess clinically 11 of these 16 patients. All presented with marked growth retardation, craniofacial anomalies, small hands and feet, hypocalcemia, hypoparathyroidism, radiologic evidence of cortical thickening of long bones with medullary stenosis, and absent diploic space in the skull. There was a history of 6 other affected sibs dying in infancy with hypocalcemic convulsions. All cases had early psychomotor retardation and absence of macrocephaly.
Using 8 consanguineous Kuwaiti kindreds, Diaz et al. (1998) performed a genomewide search for linkage to the gene causing the autosomal recessive form of KCS with polymorphic short tandem repeat markers. Significant linkage to a locus situated at 1q42-q43 with a maximum 2-point lod score of 13.30 with marker D1S2649 was obtained. Haplotype analysis of flanking markers identified recombination events defining the KCS1 locus to a region between markers D1S2800 on the centromeric boundary and D1S2850 on the telomeric boundary, an approximately 4-cM interval. All affected individuals in these unrelated kindreds were homozygous for identical alleles at D1S2649 and D1S235, suggesting a single ancestral mutation underlying the disease in these families. Haploinsufficiency at 22q11, reported in a consanguineous KCS kindred by Sabry et al. (1998), was not documented in these families. Sabry et al. (1998) had demonstrated an interstitial deletion at 22q11 by fluorescence in situ hybridization in 2 affected sibs and their unaffected mother. The clinical findings in affected individuals from 6 of the 8 pedigrees studied by Diaz et al. (1998) had previously been described by Khan et al. (1997).
The transmission pattern of KCS1 in the families reported by Parvari et al. (2002) was consistent with autosomal recessive inheritance.
Parvari et al. (2002) demonstrated homozygous or compound heterozygous mutations in the TBCE gene (see, e.g., 604934.0001) in both Kenny-Caffey syndrome and Sanjad-Sakati syndrome.
Bergada, I., Schiffrin, A., Abu Srair, H., Kaplan, P., Dornan, J., Goltzman, D., Hendy, G. N. Kenny syndrome: description of additional abnormalities and molecular studies. Hum. Genet. 80: 39-42, 1988. [PubMed: 2843457] [Full Text: https://doi.org/10.1007/BF00451452]
Diaz, G. A., Khan, K. T. S., Gelb, B. D. The autosomal recessive Kenny-Caffey syndrome locus maps to chromosome 1q42-q43. Genomics 54: 13-18, 1998. [PubMed: 9806825] [Full Text: https://doi.org/10.1006/geno.1998.5530]
Franceschini, P., Testa, A., Bogetti, G., Girardo, E., Guala, A., Lopez-Bell, G., Buzio, G., Ferrario, E., Piccato, E. Kenny-Caffey syndrome in two sibs born to consanguineous parents: evidence for an autosomal recessive variant. Am. J. Med. Genet. 42: 112-116, 1992. [PubMed: 1308349] [Full Text: https://doi.org/10.1002/ajmg.1320420123]
Khan, K. T. S., Uma, R., Usha, R., Al Ghanem, M. M., Al Awadi, S. A., Farag, T. I. Kenny-Caffey syndrome in six Bedouin sibships: autosomal recessive inheritance is confirmed. Am. J. Med. Genet. 69: 126-132, 1997. [PubMed: 9056548]
Parvari, R., Hershkovitz, E., Grossman, N., Gorodischer, R., Loeys, B., Zecic, A., Mortier, G., Gregory, S., Sharony, R., Kambouris, M., Sakati, N., Meyer, B. F., and 10 others. Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome. Nature Genet. 32: 448-452, 2002. [PubMed: 12389028] [Full Text: https://doi.org/10.1038/ng1012]
Sabry, M. A., Zaki, M., Abdul, H. S. J., Ramadan, D. J., Abdel, R. M. A., Al Awadi, S. A., al Saleh, Q. Kenny-Caffey syndrome is part of the CATCH22 haploinsufficiency cluster. J. Med. Genet. 35: 31-36, 1998. [PubMed: 9475091] [Full Text: https://doi.org/10.1136/jmg.35.1.31]
Sarria, A., Toledo, F., Toledo, J., Vega, M. L., Lopez, S., Bueno, M. Estenosis tubular diafisaria (sindrome de Kenny-Caffey): presentacion de cuatro observaciones. An. Esp. Pediat. 13: 373-380, 1980. [PubMed: 7406361]