• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Kenny-Caffey Syndrome


Last updated: November 27, 2012
Years published: 1996, 2003, 2009, 2012


NORD gratefully acknowledges Bruce D. Gelb, MD, The Gogel Family Professor of Child Health and Development, Professor of Pediatrics and Genetics & Genomic Sciences, Director, Child Health and Development Institute, Mount Sinai School of Medicine, for assistance in the preparation of this report.

Disease Overview

Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare hereditary skeletal disorder characterized by thickening of the long bones, thin marrow cavities in the bones (medullary stenosis), and abnormalities affecting the head and eyes. Most cases are obvious at birth (congenital). The primary outcome of KCS2 is short stature. Intelligence is usually normal. Individuals with KCS may also have recurrent episodes of low levels of calcium in the blood stream (hypocalcemia) that is caused by insufficient production of parathyroid hormones (hypoparathyroidism). In most cases, KCS2 is an autosomal dominant genetic disorder.

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  • dwarfism, cortical thickening of tubular bones & transient hypocalcemia
  • KCS2
  • Kenny-Caffey syndrome, dominant type
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Signs & Symptoms

KSC2 is present at birth (congenital) and low birth weight may be one of the first symptoms. This extremely rare genetic disorder is characterized by abnormalities affecting the skeleton, the head, and the eyes. Recurrent episodes of unusually low levels of calcium (hypocalcemia) in the blood are common. Most affected individuals, exhibit short stature of adult height ranging from 48 to 59 inches. Intelligence is usually normal.

KCS2 usually affects several bones of the body. Affected individuals may have thickened outer layers (cortexes) of various long bones, and abnormally thin marrow cavities (medullary stenosis). Some individuals may also have abnormal hardening of some bones (osteosclerosis).

KCS2 also affects the head and face. The anterior fontanel is a soft, membrane-covered area between the bones of an infant’s skull that usually closes about 18 months after birth. However, in KCS2, the anterior fontanel is abnormally large, closes late, and a fibrous joint between the bones in the forehead (metopic suture) is spaced wider than usual. As a result, affected infants have an abnormally large head circumference (macrocephaly) with a prominent forehead.

Several abnormalities of the eyes are also associated with KCS2. Affected individuals may have unusually small eyes (microphthalmia), leakage of cerebrospinal fluid into the optic disk of the eye may cause swelling of the disk (papilledema), and/or farsightedness (hyperopia). In some cases of this disorder, nearsightedness (myopia) has been observed. One case reported in the medical literature noted retinal and corneal calcification. Another case had bilateral optic atrophy.

Episodes of abnormally low levels of calcium in the blood (hypocalcemia) are prevalent in individuals, especially infants, affected by KCS2. Onset of hypocalcemia is usually within two to three months after birth. Other episodes may occur in relation to stress or may follow surgery or illness in an adult. Hypocalcemia is not permanent (transient) and may be caused by insufficient production of parathyroid hormones (hypoparathyroidism). These hormones, along with vitamin D and the hormone calcitonin, regulate the levels of calcium in the blood. The lack of the parathyroid hormones may be due to improper function or absence of the parathyroid glands in people with KCS2. Symptoms of hypoparathyroidism include weakness, muscle cramps; excessive nervousness; loss of memory; headaches, and abnormal sensations such as tingling, burning, and numbness of the hands. (For more information about “Hypoparathyroidism,” please see the Related Disorders section of this report.)

Low levels of calcium in the blood may also cause a condition called tetany, which is characterized by muscle cramps and periods of high-pitched respiration (stridor). Individuals with KCS2 may also exhibit abnormally low levels of phosphates in the blood (hypophosphatemia), low levels of a hormone that acts to reduce the blood level of calcium (calcitonin), low levels of circulating red blood cells (anemia), and seizures.

People affected by the recessive form of KCS2 have most of the above-mentioned abnormalities and symptoms. They may also exhibit liver disease during the first month of life (neonatal period), abnormally low levels of a certain type of white blood cell (neutropenia), improper function of another type of white blood cell (T-cells), and/or underdeveloped (hypoplastic), malformed nails.

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In most cases, KCS2 is an autosomal dominant genetic disorder. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the gender of the resulting child.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. Males have one X chromosome and if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males cannot pass an X-linked gene to their sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% to have a son affected with the disease, and a 25% chance to have an unaffected son.

Investigators have determined that the recessive form of Kenny-Caffey syndrome is the same disorder as Hypoparathyroidism-retardation-dysmophic (HRD) syndrome, which is also known as Sanjad-Sakati syndrome. HRD is an extremely rare disorder characterized by hypoparathyroidism that is present at birth (congenital); growth retardation, mental retardation; and characteristic facial abnormalities. Such facial features may include deep-set eyes, abnormally thin upper lip, abnormally small jaw (micrognathia), and a depressed bridge of the nose. Affected individuals may also have skeletal defects, abnormally thin marrow cavities (medullary stenosis), and abnormally low levels of calcium in the blood (hypocalcemia). HRD syndrome is inherited as an autosomal recessive trait. HRD syndrome is caused by disruption or changes (mutations) of the tubulin-specific chaperone E (TBCE) gene located on the long arm (q) of chromosome 1 (1q42-q43). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 1q42” refers to band 42 on the long arm of chromosome 1. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Some cases of autosomal recessive Kenny-Caffey syndrome/HRD syndrome have had parents who were related by blood (consanguineous). All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

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Affected populations

KCS2 is an extremely rare skeletal disorder that affects males and females in equal numbers. Fewer than 60 cases have been reported in the medical literature. Onset of hypocalcemia is usually within two to three months of life; the hypocalcemia is not permanent (transient). In an adult, episodes of hypocalcemia may be due to stress or follow surgery or illness. KCS2 was first described in the medical literature in 1966.

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The diagnosis of KCS2 may be confirmed by x-ray studies of the skeleton that reveal distinctive thickening of the outer layers (cortexes) of long bones along with unusually thin marrow cavities. Blood tests can detect episodes of low levels of calcium in the blood (hypocalcemia).

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Standard Therapies


The treatment of KCS2 is directed toward the specific symptoms that are apparent in each individual. Vitamin D and calcium have been prescribed for and proven effective in treating hypocalcemia. If anemia occurs, iron supplements may be prescribed. People with KCS2 should be monitored regularly by an eye doctor (ophthalmologist) who is familiar with the eye abnormalities associated with this syndrome.

Genetic counseling is recommended for affected individuals and their families. A supportive team approach for children with KCS2 may be of benefit. Such a team approach may include physical therapy and other medical, social, or vocational services. Other treatment is symptomatic and supportive.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:


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Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:263-4.

Buyse ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:1714-5.

Magalini SI, et al., eds. Dictionary of Medical Syndromes. 3rd ed. New York, NY: Lippincott Company; 1990:492.

Jones KL, ed. Smith’s Recognizable Patterns of Human Malformation. 4th ed. Philadelphia, PA: W. B. Saunders Co: 1988:345.


Parvari R, et al. Mutation of TBCE causes hypoparathyroidism-retardation-dysmorphism and autosomal recessive Kenny-Caffey syndrome. Nat Genet. 2002;32:448-52.

Diaz GA, et al. Sanjad-Sakati and autosomal recessive Kenny-Caffey syndromes are allelic: evidence for an ancestral founder mutation and locus refinement. Am J Med Genet. 1999;85:48-52.

Sabry MA, et al. Kenny-Caffey syndrome: an Arab variant? Clin Genet. 1999;55:44-49.

Sabry MA, et al. Kenny-Caffey syndrome is part of the CATCH 22 haploinsufficiency cluster. J Med Genet. 1998;35:31-36.

Diaz GA, et al. The autosomal recessive Kenny-Caffey syndrome locus maps to chromosome 1q42-q43. Genomics. 1998;54:13-18.

Tahseen K, et al. Kenny-Caffey syndrome in six Bedouin sibships: autosomal recessive inheritance is confirmed. Am J Med Genet. 1997;69:126-32.

Janke EL, et al. Anaesthetic management of Kenny-Caffey syndrome using the laryngeal mask. Paediatr Anaesth. 1996;6:235-38.

Franceschini P, et al. Kenny-Caffey syndrome in two sibs born to consanguineous parents: evidence for an autosomal recessive variant. Am J Med Genet. 1992;42:112-16.

Rebolleda FG, et al. Bilateral optic atrophy in Kenny’s syndrome. Acta Ophthalmol (Copenh). 1992;70:135-38.

Abdel-Al YK, et al. Kenny-Caffey syndrome. Case report and literature review. Clin Pediatr (Phila). 1989;28:175-79.

Bergada I, et al. Kenny syndrome: description of additional abnormalities and molecular studies. Hum Genet. 1988;80:39-42.

Enriquez EJ, et al. Congenital medullary tubular stenosis. A case report of Caffey-Kenny syndrome. Acta Orthop Scand. 1988;59:326-27.

Fanconi S, et al. Kenny syndrome: evidence for idiopathic hypoparathyroidism in two patients and for abnormal parathyroid hormone in one. J Pediatr. 1986;109:469-75.

Lee WK, et al. The Kenny-Caffey syndrome: growth retardation and hypocalcemia in a young boy. Am J Med Genet. 1983;14:773-82.

Majewski F, et al. The Kenny syndrome, a rare type of growth deficiency with tubular stenosis, transient hypoparathyroidism and anomalies of refraction. Eur J Pediatr. 1981;136:21-30.

Boynton JR, et al. Ocular findings in Kenny’s syndrome. Arch Ophthalmol. 1979;97:896-900.


Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Kenny-Caffey Syndrome; Type 2. Entry No: 127000. Last Edited May 19, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed November 21, 2012.

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