Information on the following diseases can be found in the Related Disorders section of this report:

• Ectodermal Dysplasias
• Rapp-Hodgkins Syndrome
• Growth Hormone Deficiency

The most common symptoms of Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate are: absent or irregular fingers and/or toes (ectrodactyly); and/or abnormalities of the eyes, glands, skin, teeth and urinary tract. Any combination of the following symptoms may be present in affected patients.

Missing or irregular fingers and/or toes (ectrodactyly) may be present with abnormalities of the third digit being the most common. This is sometimes referred to as split hand and/or split foot deformity. The affected digits may not be the same on each side. If ectrodactyly is not present, there may be fusion or webbing of the digits (syndactyly).

Ectodermal Dysplasias are a group of hereditary, nonprogressive syndromes in which the affected tissue derives primarily from the ectodermal germ layer. The skin, its derivatives, and some other organs are involved. The hair may be dry, light colored, fine, and sparse with absent eyebrows and eyelashes. The skin may be dry and teeth may be missing, abnormally small or lacking enamel. (For more information on this disorder choose "Ectodermal Dysplasia" as your search term in the Rare Disease Database).

Patients with EEC Syndrome may also have abnormalities of the eyes. The gland of the eye that allows tears to escape (lacrimal gland) may be missing. This gland is needed to moisten the underlining of the eyelids (conjunctiva). The opening of the glands that secrete fluid onto the back of the eyelid (meibomian gland orifice) may also be absent. An abnormally narrow passage of the channel that carries tears from the eye to the nasal cavity (nasolacrimalduct) is another condition found in some patients with EEC Syndrome. These conditions may make the patient susceptible to eye infections as well as scarring of the eye. Vision may also be affected.

An opening or fissure on the roof of the mouth or lip (cleft palate and/or cleft lip) may also be present in patients with EEC Syndrome. When cleft palate and/or cleft lip are not present, the patient may have an underdeveloped jaw, a short groove in the center of the upper lip and a broad nasal tip. Widely spaced eyes (hypertelorism) and/or slanted eyes are also sometimes present. (For more information on this disorder choose "Cleft Lip" or "Cleft Palate" as your search term in the Rare disease database).

In some patients, kidney abnormalities may also be a part of EEC Syndrome. The tube that carries urine from the kidney into the bladder (ureter) may be obstructed causing the pelvis and kidney duct to become swollen with an accumulation of urine (hydronephrosis). Kidney and pelvis inflammation and infection causing fever, chills, pain, nausea and frequent urination (pyelonephritis) may also occur. An absent kidney as well as duplication of a kidney has been reported in a few cases of EEC Syndrome.

Brown pigmented areas on the body (macules), slowed voluntary movement, an abnormally small brain and absent long bones of the arms and legs have been found in association with EEC Syndrome in a few cases.

Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate is a rare disorder thought to be inherited as an Autosomal Dominant genetic trait varying in the degree to which the symptoms appear. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate is a very rare disorder that affects males and females in equal numbers. Over seventy affected families have been reported in the medical literature of which a disproportionate number are in Denmark.

Symptoms of the following disorders can be similar to those of Ectrodactyly- Ectodermal Dysplasia-Cleft Lip/Palate. Comparisons may be useful for a differential diagnosis:

Ectodermal Dysplasias are a group of hereditary, nonprogressive syndromes in which the affected tissue derives primarily from the ectodermal germ layer. The skin, its derivatives, and some other organs are involved. Symptoms may include: eczema, poorly functioning sweat glands, sparse or absent hair follicles, absent or abnormal teeth, disfigured nails, and difficulties with the nasal passages and ears. (For more information on this disorder, choose " Ectodermal Dysplasia" as your search term in the Rare Disease Database.)

Rapp-Hodgkins Syndrome is a rare form of ectodermal dysplasia inherited as an autosomal dominant genetic trait. Major symptoms of this disorder include inability to sweat in combination with cleft lip and palate, dental abnormalities and lack of hair. (For more information on this disorder, choose "Rapp Hodgkins Syndrome" as your search term in the Rare Disease Database.)

The following disorders may be associated with Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate as secondary characteristics. They are not necessary for a differential diagnosis:

Growth Hormone Deficiency has been reported in a few cases of EEC Syndrome. Growth Hormone is manufactured in the pituitary gland. If it is missing or reduced in quantity during infancy or childhood, it results in growth retardation, short stature and other maturation delays. (For more information on this disorder choose "Growth Hormone Deficiency" as your search term in the Rare Disease Database.)

When hydronephrosis is present, temporary drainage of the urine may be necessary. Surgery may be indicated when pain, infection and/or kidney function is compromised.

Surgery may be performed on fingers and/or toes to correct webbing and malformations in some cases. Special skin care techniques may be warranted under the direction of a dermatologist, and dental treatment may be required.

Treatment of a cleft lip and/or palate requires the coordinated efforts of a team of specialists; pediatricians, dental specialists, surgeons, speech pathologists, and psychologists working together in planning the child's treatment and rehabilitation. Cleft palate may be repaired by surgery or covered by an artificial device (prosthesis) that closes or blocks the opening. Surgical repair can be carried out in stages or in a single operation, according to the nature and severity of the defect.

When hydronephrosis is present, temporary drainage of the urine may be necessary. Surgery may be indicated when pain, infection and/or kidney function is compromised.

Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.

The palate of cleft palate patients is closed during early childhood but difficulties may persist if the palate is excessively short in relation to the pharynx. Clinical trials by researchers in Florida showed that a teflon-glycerine paste applied to the rear of the pharynx in a minor surgical procedure was of substantial benefit. A rounder bump or ledge was formed, bringing the pharynx and palate into the proper relationship with each other. The hardened paste remains in place indefinitely; no side effects were observed. Children as young as eight years old were treated with this procedure. The clinical trials using the teflon-glycerine paste are now over. However, the same group of clinicians is now studying the efficacy and safety of a collagen-like substance to be used for the same purpose. For further information on this procedure contact:

William N. Williams, D.D.S.
University of Florida College of Dentistry
P. O. Box 100424
Gainesville, FL 32610
(352) 846-0801

Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 129900; Last Update:11/11/1999.

TEXTBOOKS
Thoene JG., ed. Physicians’ Guide to Rare Diseases. Montvale, NJ: Dowden Publishing Company Inc; 1995:

Jones KL., ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997: .

Behrman RE., ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996: .

JOURNAL ARTICLES
Ireland IA, et al., Ophthalmic manifestations of ectrodactyly-ectodermal dysplasia-clefting syndrome. Ophthal Plast Reconstr Surg. 1998;14:295-97.

O’Quinn JR, et al., Syndromic ectrodactyly with severe limb, ectodermal, urogenital, and palatal defects maps to chromosome 19. Am J Hum Genet. 1998;62:130-35.

Kasmann B, et al., Ocular manifestations in a father and son with EEC syndrome. Graefes Arch Clin Exp Ophthalmol. 1997;235:512-16.

Miller CI, et al., What syndrome is this? Ectrodactyly, ectodermal dysplasia, and cleft palate (EEC) syndrome. Pediatr Dermatol. 1997;14:239-40.

Gershoni-Baruch R, et al., Ectrodactyly-ectodermal dysplasia-clefting syndrome and hypothalamo-pituitary insufficiency. Am J Med Genet. 1997;68:168-72.