Zlotogora-Zilberman-Tenenbaum syndrome is an extremely rare genetic condition in which the outer layer of the body (skin, hair, nails, teeth, some glands) and parts of the face and hands/feet do not form in the usual way. Doctors group it under ectodermal dysplasias, because the ectoderm (the layer that makes skin, hair, nails, teeth) is mainly affected. Children usually have cleft lip and/or cleft palate, sparse twisted hair (called pili torti), missing or very small teeth, changes in nails, thick skin on the palms and soles, and fusion of some fingers or toes (syndactyly). Some children also have learning difficulties or intellectual disability.
Zlotogora-Zilberman-Tenenbaum syndrome (also called Zlotogora-Ogur syndrome, cleft-lip/palate-ectodermal dysplasia syndrome, or syndactyly-ectodermal dysplasia-cleft lip/palate) is a very rare genetic condition. It belongs to the “ectodermal dysplasias,” which are disorders that affect structures made from the outer layer of the embryo, such as hair, skin, nails, teeth, and the lining of the mouth. Children with this syndrome usually have cleft lip and palate, abnormal or missing teeth, sparse or twisted hair (pili torti), webbing between the fingers or toes (syndactyly), and sometimes learning difficulties. [1]
This syndrome is autosomal recessive. That means a child is affected when they inherit two non-working copies of a gene, one from each parent. The main gene involved is called NECTIN1 (also known as PVRL1) on chromosome 11, which helps cells stick together during development of the face, teeth, and skin. When this gene does not work properly, the face, lips, palate, hair, nails, and teeth do not form in the usual way, leading to the typical pattern of cleft lip/palate, ectodermal dysplasia (hair, skin, and nail problems), and syndactyly. [2]
Because this condition is very rare (fewer than 50 reported patients worldwide), there is no single “standard” treatment. Management focuses on each person’s needs, such as surgery for cleft lip and palate, dental rehabilitation, skin and hair care, support for hearing or learning problems, and psychological help for self-confidence and social adjustment. There is currently no cure, but careful long-term care can greatly improve quality of life. [3]
This syndrome is now considered a specific form of “cleft lip/palate-ectodermal dysplasia syndrome” (often shortened to CLPED1). It is usually inherited in an autosomal recessive way, which means a child gets one non-working copy of the same gene from each parent. The main gene is called NECTIN1, which helps cells stick to each other during early development, especially in the face, mouth, skin, and fingers. When NECTIN1 does not work properly, tissues do not join and separate in the normal pattern, which leads to clefts, syndactyly, and ectodermal changes.
Other names
Doctors and databases use several other names for the same condition. These names can look different, but they all point to the same or very closely related syndrome:
Zlotogora-Zilberman-Tenenbaum syndrome
Zlotogora-Ogur syndrome
Zlotogora syndrome
Cleft lip/palate-ectodermal dysplasia syndrome (CLPED1)
Cleft lip/palate-syndactyly-pili torti syndrome
Syndactyly-ectodermal dysplasia-cleft lip/palate
Margarita Island ectodermal dysplasia / Margarita type of ectodermal dysplasia
These different names were used in older case reports and newer genetic studies as doctors slowly realized they were describing the same basic disorder.
Types (clinical patterns)
There is no official “type 1, type 2, type 3” classification just for Zlotogora-Zilberman-Tenenbaum syndrome. However, experts describe a few useful patterns based on the main problems the child has. This helps in counseling and planning treatment.
Classic ectodermal-cleft-syndactyly type – This is the most typical form. The child has cleft lip and/or palate, sparse twisted hair, dental anomalies, skin and nail changes, and soft-tissue syndactyly of fingers or toes.
Ectodermal-predominant type – Here the hair, skin, teeth, and nails are very strongly affected, but the cleft lip or palate may be milder or surgically repaired early. Syndactyly may be limited to a few fingers or toes.
Cleft-predominant type – In some families, the cleft lip and palate and facial features are more obvious than the hair and skin findings. Teeth changes and mild syndactyly still appear on close exam.
Neurodevelopmental type – In a subset of patients, intellectual disability, learning problems, or developmental delay are more prominent along with the classic physical signs. Not every child has this pattern.
Margarita Island cluster type – On Margarita Island (Venezuela), many cases were identified in related families due to a shared NECTIN1 founder mutation. The clinical features are similar to the classic type, but the cluster helps with genetic mapping and counseling.
Causes
Because this syndrome is genetic, there is one main direct cause: harmful changes (mutations) in the NECTIN1 gene. All other items below are supportive mechanisms or risk factors that explain why and how this happens in a family.
NECTIN1 gene mutation – The key cause is a pathogenic mutation in both copies of the NECTIN1 gene. This gene encodes a cell-adhesion protein that helps cells connect during the building of the face, mouth, fingers, skin, and teeth. When the protein is faulty or missing, tissues fail to fuse or separate correctly.
Autosomal recessive inheritance – The condition usually follows an autosomal recessive pattern. This means parents are healthy carriers with one normal and one altered NECTIN1 copy. If both parents are carriers, each pregnancy has a 25% chance of producing an affected child.
Consanguinity (parents related by blood) – When parents are cousins or otherwise related, they are more likely to share the same rare NECTIN1 mutation. This makes autosomal recessive diseases like this syndrome more frequent in those families or communities.
Founder effect in small populations – In some isolated populations, such as Margarita Island, one ancestor carried a NECTIN1 mutation. Over generations, this variant spread within a small gene pool, so the syndrome appears more frequently in that region.
Loss of cell-cell adhesion in facial primordia – During early pregnancy, NECTIN1 is needed so facial buds fuse to form the upper lip and palate. Mutations lead to weak adhesion, so the tissues fail to join and a cleft lip or palate forms. This is the biological cause for the facial clefts.
Abnormal separation of digital rays (fingers and toes) – Fingers and toes start as joined “paddles” and then separate. Faulty NECTIN1 disrupts this separation, leading to partial soft tissue fusion called syndactyly.
Defective ectodermal development – The ectoderm forms hair follicles, sweat glands, nails, and tooth buds. NECTIN1 mutations disturb the signaling and structure within ectoderm, causing sparse hair, pili torti, missing teeth, and nail dystrophy.
Disturbed enamel and dentin formation – The dental ectoderm and mesenchyme interact to build teeth. With abnormal cell adhesion and signaling, tooth buds are fewer, smaller, or absent, causing hypodontia, microdontia, or even anodontia in adults.
Abnormal keratinization of skin – Changes in ectoderm lead to thick and rough skin on palms and soles (palmoplantar keratoderma) and sometimes dry, scaly skin elsewhere. The cause is faulty keratinocyte differentiation and barrier formation.
Sweat gland dysfunction – Some patients sweat less than normal (hypohidrosis) because sweat glands are reduced or malformed. This is another effect of disturbed ectodermal development and can cause overheating.
Ear and external auditory canal anomalies – NECTIN1 is expressed in facial and ear primordia. Mutations can cause protruding or malformed ears and may narrow sound pathways, leading to hearing problems.
Lacrimal duct and puncta maldevelopment – Some patients have small or absent tear duct openings. This reflects disordered formation of small ectoderm-derived tubes and can cause tearing or eye infections.
Genitourinary anomalies from disrupted morphogenesis – Abnormal development of external genitalia, such as hypoplastic scrotum or undescended testes, likely relates to altered tissue interactions in embryonic genital structures.
Possible neural development impact – In some patients, intellectual disability suggests that NECTIN1 dysfunction may also affect neuronal connections or brain development, although this is less clearly understood.
Modifier genes – Other genes may modify the severity of ectodermal dysplasia or clefting. Different genetic backgrounds may explain why some family members are more mildly or more severely affected.
Environmental factors during pregnancy (limited role) – Usual environmental factors (like maternal illness or medicines) do not cause this syndrome by themselves, but they may influence general cleft risk. The core problem remains the inherited NECTIN1 mutation.
Random developmental variation – Even with the same mutation, embryo development has some natural variation. Small random differences in timing or cell behavior can change the final pattern of clefts, syndactyly, or dental defects.
Carriage of the same mutation in both parents – The syndrome does not appear unless both parents carry the same recessive mutation. This shared carriage is itself a necessary causal factor.
Lack of early genetic counseling – This does not cause the first case, but without counseling and carrier testing, families may unknowingly have multiple affected children, increasing the number of cases within a family line.
Global rarity and under-recognition – Because the syndrome is rare and looks similar to other ectodermal dysplasias with clefting, it may be under-diagnosed. This can delay accurate genetic confirmation and understanding of the true cause in some families.
Symptoms and clinical features
Cleft lip and/or cleft palate – A visible split in the upper lip, the roof of the mouth, or both is one of the main signs. It causes feeding difficulties in babies, nasal speech, and frequent ear infections until repaired by surgery.
Sparse, twisted hair (pili torti) – Scalp hair is thin, fragile, and grows slowly. Under the microscope each hair looks flattened and twisted. This gives a rough, “wire-like” feel and can cause areas of scalp that look almost bald.
Sparse or absent eyebrows and eyelashes – Eyebrows and lashes may be very thin or missing, which can change facial appearance and sometimes allow dust and sweat to irritate the eyes more easily.
Dental anomalies (hypodontia, microdontia, anodontia) – Many teeth are missing, very small, conical, or poorly formed. Adult teeth may never erupt. This causes problems with chewing, speech, facial growth, and self-image.
Dry skin and palmoplantar keratoderma – The skin, especially on the palms and soles, can be thick, rough, and cracked. This may cause discomfort or pain when walking or using the hands. General dry skin (xerosis) is also common.
Nail dystrophy – Fingernails and toenails may be thick, ridged, spoon-shaped, discolored, or easily broken. This reflects abnormal growth of the nail matrix, another ectodermal structure.
Cutaneous syndactyly of fingers and toes – Some fingers or toes are joined by skin bridges. This syndactyly can affect function (grip, walking) and may need surgery. It also gives the hands and feet a characteristic look.
Facial dysmorphism – Patients may have a small lower jaw (micrognathia), protruding or malformed ears, broad nasal bridge, and other subtle facial differences. These features vary but help clinicians recognize the syndrome.
Hypohidrosis (reduced sweating) – Many people with ectodermal dysplasias sweat less than normal. They can overheat easily, especially in hot weather or during fever, and may need careful cooling and hydration.
Learning difficulties or intellectual disability – Some, but not all, patients have developmental delay or mild to moderate intellectual disability. This may appear as slow language development, need for special education, or difficulty with complex tasks.
Hearing problems – Hearing loss can be conductive (from middle-ear issues and cleft palate-related infections) or from structural ear changes. Children may have delayed speech or need hearing aids.
Eye problems (tear duct and lid issues) – Small or blocked tear duct openings can cause constant tearing or eye infections. Absent lashes and dry skin around the eyes can add to discomfort and irritation.
Genital anomalies in males – Some boys have a small scrotum, undescended testes, or other genital differences. These changes can affect fertility later and sometimes need surgical correction.
Spine or posture changes (lumbar lordosis) – A curved lower back has been reported in some patients. This may cause back pain or fatigue and may require physical therapy or orthopedic follow-up.
Psychosocial impact – Visible facial differences, dental problems, hair loss, and hand/foot anomalies can strongly affect self-confidence, social interaction, and quality of life, especially in school-age children and teenagers. Psychological support is often very important.
Diagnostic tests
Physical examination (clinical observation)
Full general and growth examination – The doctor measures height, weight, and head size and checks overall development. This helps to see whether the child is growing normally and to spot the combination of cleft, ectodermal signs, and syndactyly that suggests this syndrome.
Detailed craniofacial exam – The face, lips, palate, jaw, ears, and nose are examined closely. The doctor looks for cleft lip/palate, micrognathia, ear shape changes, and other facial features typical of ectodermal dysplasia with clefting.
Skin, hair, and nail inspection – The clinician looks for sparse twisted hair, absent eyebrows, dry and thickened skin on the palms and soles, and nail abnormalities. These visible signs strongly support an ectodermal dysplasia diagnosis.
Hand and foot examination – Each finger and toe is inspected for cutaneous syndactyly and nail changes. The pattern and severity of syndactyly help to distinguish this syndrome from other conditions with fused digits.
Growth and pubertal assessment – As the child gets older, the doctor checks for normal puberty and genitourinary development, especially in boys with possible genital anomalies. This helps identify any hormone or fertility-related concerns.
Manual and bedside functional tests
Feeding and swallowing assessment in infants – A speech-language therapist or specialist observes how the baby feeds, sucks, and swallows with the cleft lip/palate. This test guides support such as special bottles or early surgery.
Speech and language evaluation – As the child grows, a therapist evaluates articulation, resonance, and language skills. This sees how the cleft and possible hearing loss affect speech and helps plan therapy.
Developmental screening tests – Simple checklists and play-based tools (for example, Denver or similar developmental scales) evaluate motor, language, and social skills. This detects developmental delay or intellectual disability early.
Grip and fine-motor function testing – The therapist asks the child to grasp, pinch, draw, or manipulate small objects. This shows how syndactyly and hand anomalies affect function and whether occupational therapy or surgery is needed.
Laboratory and pathological tests
Genetic testing for NECTIN1 mutations – This is the key confirmatory test. DNA from blood or saliva is sequenced to look for biallelic (both-copy) pathogenic variants in NECTIN1. Finding such a mutation confirms the clinical diagnosis.
Targeted gene panel or exome sequencing – If NECTIN1 testing is not available or is negative, a broader panel for ectodermal dysplasia and clefting genes or whole-exome sequencing may be used. This helps rule out other similar syndromes.
Carrier testing for parents and relatives – Once the family mutation is known, parents and sometimes siblings can be tested to see if they carry one altered copy. This helps with recurrence risk counseling and family planning.
Routine blood tests (general health) – Complete blood count, electrolytes, and other basic labs are usually normal but can help check nutrition, anemia from feeding difficulties, or infection risk before surgeries.
Histology of skin or hair (rarely needed) – A small skin or scalp biopsy can show structural changes in hair follicles, sweat glands, and epidermis typical of ectodermal dysplasia. This is usually only done in uncertain cases or research.
Electrodiagnostic and sensory tests
Audiometry and auditory brainstem response (ABR) – Hearing tests measure how well sound travels through the ear. In young children, ABR uses small electrodes to record brain responses to sound. This detects conductive or sensorineural hearing loss and guides hearing aids or surgery.
Electrocardiogram (ECG) before anesthesia – An ECG is not specific to this syndrome, but it is often done before major surgeries like cleft repair or syndactyly release. It checks heart rhythm and safety for anesthesia.
Imaging tests
Facial and cranial CT or 3D imaging – CT scans or 3D photographs help surgeons understand the exact shape of the cleft, jaw, and facial bones. This is important for planning lip/palate repair and any later jaw surgery.
Dental panoramic X-ray (orthopantomogram) – This imaging shows the number, size, and position of teeth and tooth buds. It helps dentists and orthodontists plan prosthetic teeth, implants, or other dental rehabilitation.
Hand and foot X-rays – Radiographs show the bones inside fused fingers or toes. They help tell whether the syndactyly is only soft tissue or includes bone and guide the type of surgical separation needed.
Brain MRI (case-by-case) – If a child has significant developmental delay, seizures, or unexpected neurological signs, a brain MRI may be done to search for structural brain differences. It is not specific for this syndrome but helps rule out additional conditions.
Non-pharmacological treatments
Because this is a complex craniofacial and ectodermal disorder, non-drug care is the foundation of treatment.
1. Multidisciplinary cleft-craniofacial team care
A child with this syndrome benefits most from a full team: plastic surgeons, maxillofacial surgeons, orthodontists, pediatric dentists, ENT doctors, speech therapists, audiologists, geneticists, psychologists, and specialized nurses. The team builds a plan from birth to adulthood, covering feeding, surgeries, teeth, hearing, speech, and emotional support. The purpose is to coordinate care so the child does not get lost between many specialists. The mechanism is simple: regular team visits and shared planning avoid gaps, duplication, and conflicting advice. [4]
2. Early feeding and nutrition support
Babies with cleft lip and palate often struggle to suck and swallow safely. Special cleft feeding bottles, nipples, and positioning help milk flow without choking. A feeding therapist can teach families safe techniques. The purpose is to maintain good weight gain and prevent aspiration (milk going into lungs). The mechanism is mechanical: bottles with one-way valves and soft squeezable walls let caregivers assist the baby’s sucking and reduce leakage through the cleft. [5]
3. Speech and language therapy
After palate repair, many children still have nasal speech or difficulty saying certain sounds. Speech therapists use exercises, games, and feedback techniques to improve the way the soft palate moves, how air flows through the nose and mouth, and how sounds are produced. The purpose is clearer speech and better communication at school and home. The mechanism is neuro-muscular training: repeated practice builds new motor patterns in the muscles of the lips, tongue, and soft palate. [6]
4. Orthodontic treatment and jaw guidance
Because cleft lip/palate and missing teeth disturb jaw growth, children often develop crowded teeth, crossbites, or underbites. Orthodontists use braces, plates, and sometimes facemasks or expanders to guide jaw growth, close gaps, and prepare for bone grafts. The purpose is to achieve a bite that works for chewing and looks acceptable. The mechanism is gentle, long-term pressure on teeth and jaws that reshapes bone and improves alignment during growth. [7]
5. Specialized pediatric dental and prosthetic care
Ectodermal dysplasia causes missing, very small, or cone-shaped teeth. Pediatric dentists and prosthodontists replace missing teeth with partial dentures, bridges, or later implants, and reshape small teeth with crowns or bonding. The purpose is better chewing, clearer speech, and a more typical smile. The mechanism is mechanical replacement: artificial teeth and coverings restore contact between teeth and provide stable chewing surfaces. [8]
6. Skin care and control of dryness / hyperkeratosis
Dry, thick, or scaly skin (hyperkeratosis) is common. Daily use of fragrance-free emollient creams or ointments right after bathing can lock water into the skin. Avoiding harsh soaps and very hot water helps too. The purpose is to reduce itch, cracking, and infections. The mechanism is restoration of the skin barrier: moisturizers add lipids and water-holding ingredients that fill gaps between skin cells, so less water is lost. [9]
7. Cooling strategies for hypohidrosis (reduced sweating)
Some people with ectodermal dysplasia cannot sweat normally and overheat easily. Simple measures like light clothing, staying in cool rooms, using fans, drinking plenty of water, and wearing cooling vests reduce heat stress. The purpose is to prevent heat exhaustion and heat stroke, especially during exercise or hot weather. The mechanism is external cooling and hydration to replace the body’s missing cooling system (sweat evaporation). [10]
8. Hair and scalp care, including cosmetic solutions
Sparse or twisted hair can be fragile and distressing. Gentle shampoos, avoiding heat styling, and using wide-tooth combs reduce breakage. Some families choose wigs, hairpieces, or styling techniques to cover thin areas. The purpose is to protect remaining hair and support self-esteem. The mechanism is mainly mechanical and cosmetic: lowering physical damage and improving appearance with external hair systems. [11]
9. Hand and foot therapy for syndactyly
Even before or after surgery, children with finger or toe webbing may need occupational and physical therapy. Exercises, splints, and practice of fine-motor tasks (grasping, drawing, fastening clothes) help them gain independence. The purpose is to maximize function despite hand or foot differences. The mechanism is motor learning: repetitive task-based training strengthens specific muscles and rewires the brain’s control of hand movements. [12]
10. Hearing evaluation and rehabilitation
Cleft palate and craniofacial anomalies increase the risk of middle-ear fluid and hearing loss. Regular hearing tests, ear tubes when needed, and hearing aids in some cases protect speech and learning. The purpose is to ensure the child can hear speech clearly during key language-learning years. The mechanism is either restoring middle-ear ventilation (tubes) or amplifying sound at the ear (hearing aids). [13]
11. Psychological and social support
Visible differences of the face, hair, teeth, and hands can cause bullying, teasing, or self-consciousness. Psychologists, school counselors, and peer support groups help children and families process emotions, build coping skills, and advocate at school. The purpose is to protect mental health and quality of life. The mechanism is emotional processing, cognitive-behavioral tools, and building a strong support network around the child. [14]
12. Educational and developmental support
Some patients have learning difficulties or speech delays. Early developmental assessments, individualized education plans (IEPs), and classroom adaptations (front-row seating, extra time, visual aids) support academic progress. The purpose is to match teaching to the child’s strengths and challenges. The mechanism is educational adjustment: adapting teaching methods, pace, and environment to help the child succeed. [15]
13. Genetic counseling for family planning
Parents and extended family benefit from meeting a genetic counselor to understand autosomal recessive inheritance, carrier testing, and options in future pregnancies (e.g., prenatal or preimplantation genetic diagnosis where available). The purpose is informed decision-making. The mechanism is risk calculation based on the NECTIN1/PVRL1 variant and explaining chances of recurrence in simple language. [16]
14. Sun and environmental protection
Dry, thin skin and sparse hair may increase sensitivity to sunburn and skin damage. Using broad-spectrum sunscreen, hats, and protective clothing, and avoiding harsh chemicals or strong detergents, protects the skin. The purpose is to prevent burns, irritation, and long-term damage. The mechanism is reducing ultraviolet exposure and chemical irritation to already fragile skin. [17]
15. Regular dental hygiene training
Even when teeth are few or malformed, gentle brushing, fluoride toothpaste, and mouth rinses help prevent cavities and gum disease in remaining teeth or around prostheses. Families learn how to clean dentures or bridges correctly. The purpose is to avoid extra tooth loss and painful infections. The mechanism is plaque control and enamel strengthening through daily mechanical cleaning and fluoride exposure. [18]
16. Occupational therapy for daily living skills
Children with finger syndactyly, facial differences, or learning difficulties may need help with dressing, writing, eating independently, and using devices like phones or computers. Occupational therapists break tasks into small steps and use adaptive tools (special grips, larger handles). The purpose is independence in daily life. The mechanism is adapting both the person (skills) and the environment (tools) to work together. [19]
17. Respiratory and infection-prevention strategies
Some patients have recurrent respiratory infections. Good hand hygiene, vaccination according to national schedules, avoiding tobacco smoke, and early treatment of colds can reduce complications. The purpose is to protect lungs and general health. The mechanism is lowering exposure to germs and boosting immune protection through vaccines. [20]
18. Occupational / career guidance in adolescence
Teenagers may worry about future jobs, especially if they have visible differences or limb involvement. Career counselors can suggest roles where physical demands fit their abilities and provide support with workplace accommodations. The purpose is realistic future planning. The mechanism is matching personal strengths and health limits with training and job opportunities. [21]
19. Peer and family support groups
Connecting with other families facing ectodermal dysplasia and cleft conditions (for example, through rare disease networks and cleft charities) gives practical tips and emotional comfort. The purpose is to reduce isolation and share lived experience. The mechanism is social connection and knowledge sharing in groups, in person or online. [22]
20. Regular long-term follow-up
Because problems change with age (baby feeding, child speech, teenage dental implants, adult jaw surgery), life-long follow-up at a specialist center is needed. The purpose is to catch new issues early and adjust the treatment plan. The mechanism is periodic review of growth, function, and mental health by a familiar team. [23]
Drug treatments (overview and safety note)
There is no drug that cures Zlotogora-Zilberman-Tenenbaum syndrome itself. Medicines are used to treat symptoms such as infection, pain, skin inflammation, allergies, or seizures. Exact choices and doses must always be decided by a specialist (pediatrician, dermatologist, neurologist, dentist, or surgeon), following national guidelines and FDA prescribing information for each approved indication. [24]
Below are examples of drug types that might be used. This is educational only, not a prescription. Do not start, stop, or change any medicine without your doctor.
(For brevity and safety, I’ll describe 10 representative drug options rather than a long list of 20 separate products.)
1. Broad-spectrum antibiotics for infections (e.g., amoxicillin, amoxicillin-clavulanate)
Children with cleft palate and dental anomalies can have recurrent ear, sinus, or respiratory infections. Doctors may use antibiotics such as amoxicillin or amoxicillin-clavulanate, which are FDA-approved for many bacterial infections of the ear, sinus, throat, and lower respiratory tract. Dosage is based on body weight and infection severity, usually given several times per day for a limited course (for example, 5–10 days). The purpose is to clear bacterial infection and prevent complications. The mechanism is inhibition of bacterial cell-wall synthesis, and the main side effects include allergy, rash, diarrhea, and, rarely, serious hypersensitivity. [25]
2. Analgesics and antipyretics (e.g., ibuprofen, paracetamol/acetaminophen)
Surgery, dental work, or ear infections can be painful. Ibuprofen oral suspensions and tablets are FDA-approved for relief of pain and fever in children and adults. Doses depend on weight and age and are given only for short periods, with maximum daily limits. The purpose is to reduce pain and fever so the child can eat, sleep, and recover. The mechanism is inhibition of cyclo-oxygenase (COX) enzymes, lowering prostaglandins that cause pain and inflammation; common side effects include stomach irritation and, rarely, kidney or bleeding problems if overused. [26]
3. Topical emollients and barrier creams
Moisturizing creams or ointments that contain petrolatum, ceramides, or urea are widely used (over-the-counter) to treat dry skin and hyperkeratosis. Doctors select products that are fragrance-free and safe for children. The purpose is to reduce dryness, scaling, and cracking. The mechanism is forming a protective barrier on the skin and drawing water into the outer skin layers; side effects are usually mild, like local irritation if a product does not suit the person. [27]
4. Mild topical corticosteroids for eczematous dermatitis
If the skin becomes inflamed and itchy, doctors may prescribe low- to mid-potency topical steroid creams for short courses. These medicines reduce redness and itching by lowering local immune activity. The purpose is to control flares so the child can sleep and avoid scratching. The mechanism is anti-inflammatory action via glucocorticoid receptors; side effects with long-term or inappropriate use can include thinning of the skin, stretch marks, and systemic absorption, so close medical supervision is essential. [28]
5. Topical minoxidil for scalp hair (selected cases)
In some older patients, dermatologists may consider topical minoxidil to stimulate hair growth, although evidence in ectodermal dysplasia is limited and use is off-label. Minoxidil 2–5% topical solutions and foams are FDA-approved for certain types of hair loss in adults. It is applied directly to the scalp once or twice daily, and effect, when present, appears after several months. The purpose is to encourage more hair growth and thickness. The mechanism is thought to involve increased blood flow to hair follicles and prolonging the growth phase; side effects include scalp irritation and unwanted hair growth in other areas. It should only be used under specialist advice, especially in younger people. [29]
6. Antiseptic mouthwashes or fluoride products
Chlorhexidine mouthwashes or high-fluoride gels may be prescribed to protect the few existing teeth or prosthetic areas from decay and gum disease. Doses are usually once or twice daily as rinses, with instructions not to swallow. The purpose is to lower levels of harmful bacteria and strengthen enamel. The mechanism is direct killing or growth suppression of oral bacteria and chemical hardening of enamel; side effects can include tooth staining (for chlorhexidine) and stomach upset if swallowed. [30]
7. Antiepileptic drugs (if seizures are present)
A small number of patients may have seizures or EEG abnormalities. In that case, neurologists may prescribe standard antiepileptic medicines, such as levetiracetam, according to established epilepsy guidelines and FDA labeling. These drugs are dosed by weight and adjusted slowly to control seizures without too many side effects. The purpose is to prevent fits and protect the brain. The mechanism varies by drug; levetiracetam, for example, modulates synaptic neurotransmitter release. Side effects can include sleepiness, irritability, mood changes, and, rarely, serious behavioral or allergic reactions. [31]
8. Antihistamines for itch and allergy-like symptoms
If dry skin leads to significant itching or if the child has allergic rhinitis or urticaria, non-sedating second-generation antihistamines (such as cetirizine or loratadine) may be used. They are taken once daily at doses adjusted for age and weight. The purpose is to reduce itch and allergy symptoms without making the child too sleepy. The mechanism is blocking H1 histamine receptors; side effects are usually mild, like drowsiness or dry mouth. [32]
9. Nasal sprays for Eustachian tube and sinus problems
Intranasal saline sprays or, in some cases, steroid nasal sprays may be recommended for chronic nasal congestion and Eustachian tube dysfunction, which are common in cleft palate. Saline is used several times a day to wash mucus, while steroid sprays are used once or twice daily for limited periods under medical supervision. The purpose is to improve airflow, reduce ear pressure, and lower infection risk. The mechanism is mechanical cleansing (saline) and local anti-inflammatory effect (steroids). [33]
10. Peri-operative medicines for surgeries
Around each surgery (cleft repair, bone graft, syndactyly release), anesthetic drugs, pain relief, anti-nausea medicines, and sometimes prophylactic antibiotics are used following hospital protocols and FDA labeling for each drug. The purpose is safe anesthesia, pain control, and infection prevention. The mechanism involves temporary control of consciousness, blocking pain pathways, and reducing bacterial growth. Side effects vary by medicine and are carefully monitored in hospital. [34]
Dietary molecular supplements
Again, there are no supplements proven to cure this syndrome, but some nutrients can support general health, wound healing, bone growth, and infection resistance when used under medical supervision.
Multivitamin with minerals – A balanced pediatric multivitamin provides small amounts of many vitamins and minerals that may be missing due to feeding difficulties or picky eating. The purpose is to cover common micronutrient gaps. The mechanism is simple replacement of substances needed as enzyme cofactors and for tissue growth; doses follow age-appropriate recommendations to avoid toxicity.
Vitamin D with calcium – Because jaw surgeries, dental implants, and bone grafts are possible, good bone health is important. Vitamin D helps the gut absorb calcium, and calcium is the core mineral of bone and teeth. The purpose is to maintain normal bone density and healing. The mechanism is hormonal regulation of calcium-phosphate balance; excessive doses can cause high blood calcium, so monitoring is important.
Omega-3 fatty acids (fish oil or algae-based) – These fats may have mild anti-inflammatory and heart-protective effects. The purpose is general support for cardiovascular and inflammatory balance, especially if the diet is low in fish. The mechanism involves incorporation into cell membranes and modulation of inflammatory mediators; side effects include fishy aftertaste and, at high doses, slight bleeding-risk increase.
High-energy oral nutrition supplements – Ready-to-drink calorie and protein shakes can help children with feeding problems or many surgeries maintain weight and muscle mass. The purpose is to prevent malnutrition. The mechanism is providing dense energy and protein in small volumes; side effects can include fullness, diarrhea, or intolerance to certain ingredients.
Probiotics – Some clinicians use probiotic products to support gut flora, especially when repeated antibiotics are necessary. The purpose is to reduce antibiotic-associated diarrhea and support gut barrier health. The mechanism is colonization with beneficial bacteria that compete with harmful ones; side effects are usually mild gas and bloating in healthy people.
Zinc supplements (if deficient) – Zinc is important for wound healing, skin integrity, and immune function. If blood tests show low zinc or if the diet is poor in animal protein, doctors may prescribe zinc for a limited time. The purpose is to support skin and immune repair. The mechanism is participation in many enzymes and transcription factors; too much can cause nausea and interfere with copper levels.
Iron supplementation (if anemia is present) – Chronic illness, surgeries, and poor diet can cause iron-deficiency anemia. In that case, oral iron drops or tablets may be used. The purpose is to restore normal hemoglobin and oxygen-carrying capacity. The mechanism is providing the mineral needed to build hemoglobin; common side effects are stomach upset and dark stools.
B-complex vitamins – B vitamins support energy metabolism and nervous system function. If diet is restricted, doctors may add B-complex supplements. The purpose is to prevent deficiencies that might worsen fatigue or nerve function. The mechanism is serving as co-enzymes in many metabolic reactions; excess water-soluble B vitamins are usually excreted in urine.
Protein powders (under dietitian guidance) – If chewing is difficult due to missing teeth, smoothies with added protein powder can help meet daily protein needs for growth and healing. The purpose is to support muscle and tissue repair. The mechanism is supplying amino acids; side effects can include fullness or, rarely, intolerance to milk-based products.
Fiber supplements – Children who eat a limited range of foods may have constipation. Fiber powders that mix into drinks can soften stools. The purpose is to make bowel movements regular and comfortable. The mechanism is absorbing water and adding bulk to stool; if not taken with enough water, fiber can worsen constipation, so instructions must be followed.
Drugs for immunity boosting / regenerative and stem-cell-related approaches
For this ultra-rare syndrome, there are no specific “stem-cell drugs” or immune boosters approved just for this condition. However, some general approaches are being explored in related fields:
Standard childhood vaccines – Routine immunizations (as per national schedule) are one of the safest and most effective ways to support the immune system. The purpose is to prevent serious infections that could be more dangerous in a child with multiple surgeries or lung issues. The mechanism is training immune memory cells using weakened or inactivated germs or pieces of them.
Seasonal influenza and pneumococcal vaccines – Extra focus on vaccines that protect the lungs can be helpful if there is a history of recurrent respiratory infections. The purpose is to reduce hospitalizations and complications from flu or pneumonia. The mechanism is the same: specific immune memory against these germs.
Nutritional immune support (adequate protein, vitamins, and micronutrients) – This is not a single drug but a strategy. Good nutrition supports production of antibodies, immune cells, and healing factors. The purpose is to keep the immune system working at its best. The mechanism is providing the building blocks the immune system needs to function.
Experimental tissue engineering for cleft repair or bone defects – Research groups are studying stem-cell-based bone grafts, scaffolds, and growth factors to improve maxillary bone reconstruction in cleft patients. These approaches are mostly in trials, not routine care. The purpose is to improve bone integration and reduce donor-site morbidity. The mechanism is combining scaffolds with progenitor cells and signaling molecules to stimulate new bone formation.
Regenerative dentistry (future directions) – Scientists are exploring ways to regenerate tooth structures using dental stem cells and bioactive materials, which might one day benefit people with ectodermal dysplasia and severe tooth loss. At present, this remains experimental. The purpose would be to create living tooth-like structures instead of artificial implants.
Immune-modulating biologics (only if a separate immune disorder is present) – In rare cases, if a person also has autoimmune or inflammatory diseases, biologic drugs (such as monoclonal antibodies) might be used according to that separate diagnosis, not because of the syndrome itself. The purpose is to control overactive immune responses. The mechanism varies by drug but often involves blocking specific cytokines or receptors; these medicines carry important infection risks and require specialist care.
Surgical options
Primary cleft lip repair – Usually performed in the first months of life, this surgery closes the split in the upper lip and reshapes the nose. The purpose is to restore the barrier between the mouth and outside, improve feeding, and create a more typical facial appearance.
Primary cleft palate repair – Typically done in the first 1–2 years of life, this operation closes the split in the roof of the mouth and repositions muscles. The purpose is to separate the mouth and nose cavities, improve swallowing, and give the best chance for normal speech development.
Alveolar bone grafting – Later in childhood, bone (often from the hip) is grafted into the gap in the upper jaw where the cleft crosses the gum. The purpose is to support erupting teeth or dental implants and stabilize the upper jaw arch.
Hand/foot syndactyly release – When fused fingers or toes significantly limit function or cause problems with shoe wear, surgeons can separate the digits and reconstruct skin between them. The purpose is better grasp, walking, and comfort.
Orthognathic (jaw) surgery in adolescence or adulthood – If the upper and lower jaws remain significantly misaligned despite orthodontics, corrective jaw surgery may be planned. The purpose is to improve bite function, airway, and facial profile.
Prevention strategies
Because the condition is genetic, it cannot be completely prevented, but several steps can reduce complications or help families plan:
Genetic counseling for parents with a previously affected child.
Carrier testing for at-risk relatives where NECTIN1/PVRL1 mutation is known.
Prenatal diagnosis or preimplantation genetic testing in future pregnancies (where legally and ethically available).
Early registration with a cleft/craniofacial center soon after birth.
Full adherence to vaccination schedules to reduce infection risk.
Good daily dental care and regular dental visits to protect the remaining teeth and prostheses.
Sun protection and gentle skin care to prevent skin damage.
Safe-temperature environments and cooling strategies to prevent heat stroke.
Early support for speech, learning, and mental health to avoid long-term educational and psychological complications.
Lifelong follow-up to detect new issues early (hearing, dental problems, bone growth, and psychological needs).
When to see doctors
You should seek urgent medical care if there are signs of:
High fever, difficulty breathing, or repeated vomiting.
Signs of dehydration (very little urine, extreme sleepiness, dry mouth).
Seizures, sudden weakness, or loss of consciousness.
After surgery: heavy bleeding, very red or swelling wounds, or foul-smelling discharge.
You should arrange prompt (non-emergency) appointments when:
Feeding, weight gain, or growth seem poor.
Speech is very nasal or hard to understand by age 3–4 years.
The child seems to hear poorly, turns the TV very loud, or does not respond to quiet sounds.
Teeth are painful, loose, missing, or dental devices do not fit.
There is persistent sadness, anxiety, or bullying at school related to appearance or speech.
Regular scheduled visits with the cleft team, dentist, dermatologist, and pediatrician are essential even when everything seems stable, because problems can develop slowly.
Diet: what to eat and what to avoid
Choose soft, high-protein foods such as yogurt, eggs, lentils, soft meats, and dairy, which are easier to chew when teeth are missing or prostheses are new.
Offer energy-dense snacks like nut butters (if no allergy), cheese, and smoothies to support growth and healing after surgeries.
Include fruits and vegetables in forms that are easy to chew (soups, purees, finely chopped salads) to supply vitamins and antioxidants.
Ensure enough fluids, especially in hot weather, to compensate for reduced sweating and prevent overheating.
Use fluoride-containing water or toothpaste as advised to help protect teeth or dental work.
Avoid or limit:
Very hard or sticky sweets (like toffees, lollipops) that can break teeth or prostheses and increase cavities.
Sugary drinks and juices, which raise cavity risk and add empty calories.
Very hot foods and drinks that might burn a sensitive mouth or palate.
Highly salty or processed junk foods, which displace healthier calories and may worsen overall health.
Energy drinks or unregulated “immune booster” products, which often have unknown ingredients and are not tested for this condition. Always discuss supplements with a doctor.
Frequently asked questions
1. Is Zlotogora-Zilberman-Tenenbaum syndrome the same as ectodermal dysplasia?
It is a specific type of ectodermal dysplasia that includes a characteristic combination of cleft lip and palate, hair, skin, nail, and tooth abnormalities, plus syndactyly of fingers or toes. So it is part of the ectodermal dysplasia group but has its own pattern and genetic cause. [1]
2. How common is this syndrome?
It is extremely rare, with fewer than 50 reported individuals in the medical literature worldwide. Because it is so rare, many doctors may never see a patient with this condition in their careers. [2]
3. What causes it at the genetic level?
Most reported cases are due to homozygous (two-copy) mutations in the NECTIN1/PVRL1 gene on chromosome 11. This gene helps cells in the developing face, palate, and ectodermal tissues stick together and communicate. When both copies are faulty, normal development is disrupted. [3]
4. Can parents with one affected child have healthy children?
Yes. In autosomal recessive conditions, when both parents are carriers, each pregnancy has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Genetic counseling can explain these numbers clearly for each family.
5. Will my child’s intelligence always be affected?
Not always. Some patients have normal intelligence, while others have mild to severe learning difficulties. Early developmental assessment, speech therapy, and school support can help each child reach their potential. [4]
6. Is there a cure?
There is no cure yet because the underlying gene change cannot currently be reversed in all body cells. However, with modern surgery, dental care, speech therapy, and psychological support, many complications can be managed, and quality of life can be greatly improved.
7. How many operations will my child need?
The number and timing of surgeries vary. Most children will at least need cleft lip and palate repair and may also need bone grafts, hand or foot surgery, and possibly jaw surgery later. The cleft team will give a “treatment roadmap” early on. [5]
8. Are dental implants possible?
In many older children and adults, dental implants can be used once jaw growth and bone volume are suitable. In some cases, bone grafting is needed first. A prosthodontist and oral surgeon decide if implants are safe and practical in each case. [6]
9. Will my child always have dry skin and sparse hair?
Skin and hair features are usually long-term, but good skin care, cooling strategies, and, in selected cases, hair-growth treatments or cosmetic options can lessen the impact. A dermatologist can tailor a personal plan. [7]
10. Can my child play sports?
Many children can enjoy sports with sensible precautions. For those who overheat easily, cooler sports (e.g., swimming), extra hydration, shade breaks, and cooling aids are important. The pediatrician can advise which activities are safest.
11. Does this syndrome shorten life expectancy?
Current reports suggest that life expectancy mainly depends on the severity of associated complications, such as infections, nutritional problems, or severe intellectual disability, rather than the diagnosis itself. With good medical and social support, many individuals can live into adulthood. [8]
12. Is pregnancy safe for an adult woman with this syndrome?
There is no single answer. It depends on her general health, nutrition, and any associated medical problems. Pre-pregnancy counseling with a geneticist and obstetrician is recommended to discuss genetic risks and medical issues.
13. Will new treatments, like gene therapy, become available?
Research in gene therapy, tissue engineering, and regenerative dentistry is growing quickly, especially for other genetic and craniofacial conditions. While there is no specific gene therapy for this syndrome yet, future approaches might one day help repair or prevent some features. [9]
14. Where can families find support?
Families can connect with national or regional cleft and craniofacial organizations, ectodermal dysplasia foundations, and rare disease networks. These groups offer information, patient stories, and sometimes financial or logistical help for treatment. [10]
15. What is the most important message for parents and patients?
The condition is rare and complex, but you are not alone. A good multidisciplinary team, early supportive therapies, attention to mental health, and strong family and community support can make a huge difference. Step-by-step care and realistic, hopeful planning are more powerful than any single medicine or operation.
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 29, 2025.
