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Congenital Athymia

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Last updated: 12/6/2023
Years published: 2019, 2022, 2023


Acknowledgment

NORD gratefully acknowledges Gioconda Alyea, Brazilian MD, MS, National Organization for Rare Disorders and M. Louise Markert, MD, PhD, Emeritus Professor of Pediatrics, Duke University Medical Center, for assistance in the preparation of this report.


Disease Overview

Summary

Congenital athymia is a rare disease characterized by the absence of a functioning thymus. It can occur as an isolated finding, or it can be part of a genetic syndrome.

Most infants with congenital athymia have chromosome 22q11.2 deletion syndrome or CHARGE syndrome. Both disorders have symptoms affecting multiple body systems. NORD has separate reports on 22q11.2 deletion syndrome and CHARGE syndrome in the Rare Disease Database.

Congenital athymia can also result from changes (pathogenic variants or mutations) in genes that impact thymic organ development such as FOXN1 and PAX1 or from variants in genes that are involved in development of the entire midline region of the body, such as TBX1, CHD7 and FOXI3.

In addition, infants exposed to retinoic acid during pregnancy and infants born to diabetic mothers have a higher risk for congenital athymia.

People affected with congenital athymia have profound immunodeficiency, increased susceptibility to infections, and frequently, autologous graft-versus-host disease (GVHD) which is a life-threatening complication that can occur after certain stem cell or bone marrow transplants, a medical treatment that replaces the bone marrow with healthy cells.

Introduction

The thymus is a gland located on top of the heart. The thymus produces specialized white blood cells called T cells that fight infections, especially viral infections. The T cell count is highest in infants in the first two years of life and then slowly decreases over time. In adults over the age of 60, the thymus is mostly replaced by fat. Children without a thymus are extremely deficient in T cells and very susceptible to infections. Affected babies have chronic or recurrent infections including candidiasis, skin, pulmonary and urinary tract infections, chronic diarrhea and have difficulty growing and gaining weight (failure to thrive).

Without treatment, some affected children may not survive. Thymus transplantation may be a cure for this condition.

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Signs & Symptoms

Absence or underdevelopment of the thymus results in an increased susceptibility to viral, fungal and bacterial infections (immunodeficiency). The degree of susceptibility can vary. Specific symptoms vary depending upon the type of infection, overall health of the infant and other factors. Respiratory infections are common, often leading to respiratory distress. Opportunistic infections are also common. The term “opportunistic infection” refers either to infections caused by microorganisms that usually do not cause disease in individuals with a fully functioning immune system or to widespread (systemic) overwhelming disease by microorganisms that typically cause only localized, mild infections. Not only are affected infants more susceptible to infections, but their bodies also cannot effectively fight off the infections.

Because congenital athymia can be isolated (very rarely) or can be a part of several conditions, the specific signs and symptoms depend on the specific diagnosis. The following conditions can include congenital athymia:

 T-cell immunodeficiency with thymic aplasia is a rare disorder in which children have no detectable thymus (athymia) without other anomalies. It is caused by changes (mutations or pathogenic variants) in the FOXN1 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a variant in a gene occurs, the protein product may be faulty, inefficient, absent or overproduced. Depending upon the functions of the protein, this can affect many organ systems of the body.

The FOXN1 gene provides instructions for making a protein that attaches to specific regions of DNA and regulates the activity of other genes. Based on this action, the FOXN1 protein is called a transcription factor.

The FOXN1 protein is important for the development of the skin, hair, nails and immune system. Studies suggest that this protein helps guide the formation of hair follicles and the growth of fingernails and toenails. The FOXN1 protein also plays a critical role in the formation of the thymus.

Symptoms of T-cell immunodeficiency with thymic aplasia may include:

  • Aplasia of the thymus in all patients
  • Cellular immunodeficiency, which refers to the lack of cellular immune response, an immune response that does not involve antibodies but is mediated with the activation of T-lymphocytes and other cells when the body needs to defend itself against a virus, bacteria or fungus
    • Decrease in T cell count and proliferation
    • Severe T-cell immunodeficiency
  • Recurrent infections
  • Difficulty growing and gaining weight (failure to thrive)
  • Opportunistic infections
  • Pneumonia
  • Recurrent bacterial infections
  • Recurrent infection of the gastrointestinal tract
  • Severe infection
  • Severe viral infection
  • Diarrhea
  • Fungal infections

Variants in the FOXN1 gene can also cause T-cell immunodeficiency, congenital alopecia, and nail changes (also known as nude SCID, FOXN1 deficiency, alymphoid cystic thymic dysgenesis and Winged helix deficiency), which is characterized by congenital athymia (resulting in severe T-cell immunodeficiency), congenital complete hair loss and fingernails or toenails that are deformed, thickened or discolored (dystrophic nails). The symptoms begin during the first months of life with severe, recurrent, life-threatening infections and low or absent circulating T cells. The signs and symptoms may include:

  • Thymic aplasia
  • T-cell immunodeficiency (low or absent T cells) with increased susceptibility to viral, fungal and opportunistic infections as well as live vaccines
  • Failure to thrive
  • Poor growth
  • Complete hair loss (alopecia)
  • No eyelashes
  • No eyebrows
  • Oral candidiasis
  • Recurrent respiratory infections
  • Gastroenteritis with diarrhea
  • Redness and scaling of the skin (erythroderma)
  • Fingernails or toenails that are deformed, thickened or discolored (dystrophic nails)
  • Depressions or dimples in the fingernails or toenails (nail pitting).

Although B-cells are typically present in normal numbers, antibody production is compromised in the absence of T-cells, which makes the patients susceptible to infections with encapsulated bacteria such as Streptococcus pneumoniae, Klebsiella, Haemophilus influenzae, Neisseria meningitidis and Pseudomonas aeruginosa.

 Congenital athymia can also be found in several syndromes such as:

  • Complete DiGeorge syndrome also known as complete DiGeorge anomaly
  • 22q11.2 deletion syndrome
  • CHARGE syndrome

Most infants with congenital athymia have a chromosome 22q11.2 deletion syndrome or CHARGE syndrome.  It is now recognized that 22q11.2 deletion syndrome includes DiGeorge syndrome and other conditions. However, the term DiGeorge syndrome is still used for people who have clinical features of 22q11.2 deletion syndrome but do not have an identified 22q11.2 deletion. In addition, many but not all infants with 22q11.2 deletion syndrome and CHARGE syndrome have T cell counts less than the 10th percentile for age and are often referred to as having DiGeorge syndrome.

Complete DiGeorge syndrome is characterized by absence or underdevelopment (hypoplasia) of the thymus resulting in very low T cell counts. Absence or underdevelopment of the thymus results in an increased susceptibility to viral, fungal and bacterial infections (immunodeficiency).

Additional signs and symptoms include:

  • Heart defects that are present at birth (congenital heart disease)
  • Hypoparathyroidism, a rare condition in which the parathyroid glands, that are in the neck, fail to produce enough parathyroid hormone, which plays a role in regulating the levels of calcium and phosphorus in the blood
    • Low levels of calcium in the blood can result in seizures
  • Softening of the tissues of the voice box (larynx), a condition called laryngomalacia that can cause noisy breathing and eating difficulties

Chromosome 22q11.2 deletion syndrome is associated with a range of problems including:

  • Heart defects that are present at birth (congenital heart disease)
  • Palate abnormalities
  • Immune system dysfunction including autoimmune disease
  • Low calcium (hypocalcemia)
  • Other endocrine abnormalities such as thyroid problems and growth hormone deficiency
  • Gastrointestinal problems
  • Feeding difficulties
  • Kidney abnormalities
  • Hearing loss
  • Seizures
  • Skeletal abnormalities
  • Minor facial differences
  • Learning and behavioral differences

CHARGE is an acronym that stands for:

  • [C]oloboma
  • congenital [H]eart defects
  • choanal [A]tresia
  • growth [R]etardation
  • [G]enital hypoplasia
  • [E]ar anomalies or deafness.

Congenital athymia can also be found in people who have variants in the following genes:

  • TBX1 gene which cause DiGeorge syndrome
  • TBX2 gene which cause vertebral anomalies and variable endocrine and T-cell dysfunction, a syndrome characterized by skeletal malformations primarily involve the vertebrae, and endocrine abnormalities involving parathyroid hormone, growth hormone, and the thyroid gland have been reported as well as T-cell abnormalities and thymus gland aplasia or hypoplasia
  • PAX1 gene which cause otofaciocervical syndrome-2 with T-cell deficiency (OTFCS2), a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders and mild intellectual disability, as well as athymia or an underdeveloped thymus with T-cell immunodeficiency and recurrent, sometimes fatal, infections

Infants exposed to retinoic acid during pregnancy have a higher risk for congenital athymia. Infants born to diabetic mothers have a higher risk for congenital athymia. Infants with congenital athymia who are born to diabetic mothers may also have only one kidney (renal agenesis).

Researchers have also identified an atypical form of congenital athymia. Affected infants, in addition to immunodeficiency, develop a red, often itchy, rash and enlargement of the lymph nodes (lymphadenopathy).

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Causes

Congenital athymia refers to the absence of the thymus. To understand the problems related to this condition, it can be helpful to think of the thymus as a schoolhouse. In a child who has a thymus, stem cells from the bone marrow go to the thymus (the “schoolhouse”) to develop into T cells. The developing T cells learn to not attack the infant’s body (self) and to fight infections. If the developing T cells are successful learning these two lessons, they “graduate,” and leave the schoolhouse. The graduates have special proteins on the surface of the cell that are called “naïve” T cells. After the naïve T cells fight an infection, they lose the special markers and are called memory T cells. Memory T cells can quickly fight an infection if it recurs.

In congenital athymia, there is no thymus (no schoolhouse). However, stem cells in the bone marrow develop into cells that look like T cells but are missing the “naïve” T cell markers. These “atypical” T cells have not gone to “school” and have not learned what is “self.” The atypical T cells then attack the body causing rash, and often also diarrhea or liver damage.

As mentioned before, congenital athymia can have different causes, and it may occur as an isolated problem or can be part of other conditions.

Congenital athymia can result from genetic changes that are (1) specific to thymic organ development or (2) involved in the broader development of the entire midline region of the body.

Genetic changes specific to thymic organ development

  •  Congenital athymia related to FOXN1gene variants

The FOXN1 gene is the most well-known gene specific to thymic development.

Variants in the FOXN1 gene result in congenital athymia, congenital alopecia and nail dystrophy. When the variants affect both copies of the FOXN1 gene, the result is loss of function of the protein and the symptoms are more severe.

When the variant affects only one of the copies of the FOXN1 gene the affected child may not have complete congenital athymia and lymphopenia tends to improve over time.

When both copies of the gene are variants, but the variants are different, this may cause the condition known as T-cell immunodeficiency with thymic aplasia which has only been reported in two children.

  • Congenital athymia related to PAX1gene variants

The PAX1 gene is a member of the paired box family of transcription factors that are important for differentiation of tissues.

Variants of the PAX1 gene cause autosomal recessive otofaciocervical syndrome type 2 (OTFCS2).

Genetic changes that impact development of the entire midline region

The most common genetic syndromes associated with defects in thymus development are 22q11.2 deletion syndrome and CHARGE syndrome. The genes implicated in these respective disorders, TBX1 and CHD7, play a role in development of the entire midline region, and as a result, patients with these syndromes have many different symptoms.

  •  TBX1gene variants are thought to be the main cause for the congenital defects associated with 22q11.2 deletion and DiGeorge syndrome (DGS).
  • CHD7gene variants have been implicated in CHARGE syndrome (about 60–65% of patients with CHARGE have a variant in the CHD7 gene). Thymic aplasia has been reported in 27 of 59 patients with CHARGE and in 16 of 36 patients with a proven variant in CHD7. CHARGE syndrome has also been reported in patients with congenital athymia who do not have CHD7 gene variants.

Other possible genes implicated in thymus development include TBX2 and FOXI3. TBX2 gene variants cause vertebral anomalies and variable endocrine and T-cell dysfunction. Additionally, FOXI3 was recently implicated in a 22p11.2 microdeletion in several patients with features resembling DGS.

Environmental causes

Several environmental causes are associated with congenital athymia. Diabetic embryopathy is associated with altered fetal thymus size and other congenital abnormalities such as renal agenesis and butterfly vertebrae.

When a baby has been exposed to retinoids during pregnancy, there is an increased risk for thymus developmental abnormalities such as thymic aplasia and ectopia and hypoplasia. Retinoids, such as isotretinoin (Accutane), are drugs prescribed for severe cystic acne.

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Affected populations

Congenital athymia affects both males and females. The exact incidence and prevalence of this disorder are unknown.

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Diagnosis

A diagnosis of congenital athymia is based upon identification of characteristic symptoms, a detailed patient and family history and a thorough clinical evaluation.

Some babies are diagnosed with newborn screening. All 50 states have added newborn screening for severe combined immunodeficiency (SCID), but some states do not require that every hospital include the newborn screening for SCID. Newborn screening identifies infants with low levels of T cells, which can lead to identification of newborns with athymia. Immune function is determined by measurement of TRECs, which are products formed during T cell receptor rearrangement in the thymus. Low or undetectable TRECs are considered a positive finding during SCID screening. Babies who test positive are put in isolation right away.

All babies who have a positive newborn screening then have complete and differential blood counts and lymphocyte phenotyping by flow cytometry.

Blood tests can identify low number of T-cells (T-cell lymphopenia), CD8+ T-cell depletion and normal humoral immunity (antibodies) in most babies. CD8+ T cells (often called cytotoxic T lymphocytes, or CTLs) are very important for immune defense against viruses and bacteria, and for tumor surveillance.

Flow cytometry of the peripheral blood means that the peripheral blood (the blood that is circulating through the body) is studied using a machine called a flow cytometer. The flow cytometer can determine the number and percentage of various cell types in the blood sample. Very low T cell numbers shortly after birth are a sign of congenital athymia.

The diagnosis of the absence of the thymus cannot be made with a chest X-ray or computerized tomography (CT) scan or by visualization during heart surgery because the thymus can be small or may be found in a different part of the body such as in the neck (ectopic thymus).

FOXN1 deficiency should be suspected in infants who have clinical and/or laboratory evidence of immunodeficiency associated with congenital alopecia and nail dystrophy.

Children can also be evaluated for other symptoms that may reveal that the athymia is part of a syndrome, such as complete DiGeorge syndrome or CHARGE syndrome.

Genetic testing to identify FOXN1 gene variants and variants in other genes associated with thymic problems can confirm the diagnosis.

The diagnosis of atypical congenital athymia is made when a patient has the rash and high numbers of T cells but no, or very few, naïve T cells in the blood.

Clinical Testing and Work-Up

Affected children should be actively screened for viral, fungal and bacterial infections with microbiological examination of respiratory secretions and stools and imaging; blood should also be tested for the presence of Epstein Barr (EBV) and cytomegalovirus (CMV) nucleic acid.

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Standard Therapies

Treatment

Treatment requires the coordinated efforts of a team of specialists. Pediatricians, physicians who specialize in diagnosing and treating immune system disorders (immunologists), physicians who specialize in diagnosing and treating blood disorders (hematologists), physicians who specialize in diagnosing and treating endocrine disorders (endocrinologists) and other healthcare professionals may need to work together for the best plan treatment.

The first priority is to reduce the risk of infection until the underlying immune deficiency can be corrected.

Treatment and management may include:

  • Isolation of the newborn baby at the hospital as soon as the diagnosis is suspected
    • Iisolation must continue at home, which includes frequent handwashing, changing clothes/sanitizing upon re-entering the house and restricting visitors in the home
  • Medication with prophylactic antibiotics to prevent infections
  • Immunoglobulin replacement (although patients with congenital athymia often have normal numbers of B cells, their B cell function is usually reduced – B cells create a type of protein called an antibody which fight foreign substances, such as toxins, to neutralize them)
  • Avoidance of live vaccines (live vaccines are a weakened for of the germ that cause a disease) but in cases of partial T cell deficiency some live vaccines can be received
  • Making sure that all blood products given to the affected person are not contaminated with cytomegalovirus (viruses that cause chickenpox, herpes simplex and mononucleosis) and considering irradiating blood products to prevent graft-versus-host disease (GVHD)
  • Immunosuppression (such as medication known as steroids or calcineurin inhibitors) for inflammation and to reduce the risk of GVHD
  • Anti-thymocyte globulin prior to receiving a cultured thymus tissue implantation to prevent and treat the body from rejecting the thymus tissue

The main form of treatment is implantation of cultured thymus tissue. In 2021, the U.S. Food and Drug Administration (FDA) approved the use of cultured thymus tissue (Rethymic) for treatment of pediatric patients with congenital thymia. Rethymic is composed of thymus tissue from infant donors that has been processed and cultured. Many tissue slices, after culture, are implanted into the thigh muscle of an athymic patient to help improve immune function. (The word “implant” is used in this report because the thymus tissue is processed in a laboratory for at least 12 days prior to use. The word “transplant” refers to an organ taken out of one individual in an operating room which is immediately brought to a neighboring operating room and placed into the recipient.).

The thymus tissue needed for this product is obtained during heart surgery on an infant. Thymus tissue may need to be removed during infant heart surgery to allow for the surgeon to access the heart. Instead of being discarded, it is put in a sterile container and sent to a laboratory. The tissue is processed into slices and maintained in culture for 12 to 21 days and the cultured tissue is then brought to the operating room and implanted into the child’s quadriceps muscle (this location was chosen because it has a good blood supply to get oxygen and nutrients to the thymus tissue slices). The implanted cultured thymus tissue slices will produce the T cells missing from the affected infant’s immune system (it takes about six months for the immune system to begin functioning and over 6-9 months, babies will develop T cells that are able to fight infections). Prior to using Rethymic patients are in isolation and continue to receive immunoglobulin replacement and prophylactic antimicrobials.

The most common adverse effect of this therapy is autoimmunity in the first year prior to development of diverse T cells. Autoimmunity is when the body’s immune system accidentally harms healthy tissue. Autoimmunity is treatable and is less frequent after the first year after implantation.

In the United States, Duke Children’s Hospital is the only medical center that performs the implantation of the thymus tissue.

Though not directly related to their immunodeficiency, children with congenital athymia also require management for other health problems if they have a genetic syndrome.

For example, children who have congenital athymia as part of a complete DiGeorge syndrome may need:

  • Calcium supplements or a synthetic version of vitamin D3 called calcitriol for the hypoparathyroidism that may lead to newborn seizures
  • Surgical care for heart defects
  • Tracheostomy for the affected infants with laryngomalacia or aspiration, which is the creation of a surgical opening in the neck to gain access to the windpipe (trachea) where a tube is placed into this opening to allow breathing
  • Gastrostomy tube (a tube going into the stomach) for feeding the child
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Clinical Trials and Studies

Researchers have studied hematopoietic stem cell transplantation (HSCT) for the treatment of infants with congenital athymia. Stem cells are special cells found in bone marrow that manufacture different types of blood cells such as neutrophils eosinophils, monocytes and lymphocytes. Patients with congenital athymia do not have abnormal stem cells. Hematopoietic stem cell transplantation has not been found to be an effective treatment. Stem cells can’t turn into T cells in a patient lacking a thymus.

Information on current clinical trials is posted on the Internet at https://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:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

 

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References

JOURNAL ARTICLES

Markert ML, Gupton SE, McCarthy EA. Experience with cultured thymus tissue in 105 children. J Allergy Clin Immunol. 2022;149:747-757. https://pubmed.ncbi.nlm.nih.gov/34362576/

Collins C, Sharpe E, Silber A, Kulke S, Hsieh EWY. Congenital athymia: Genetic etiologies, clinical manifestations, diagnosis, and treatment. J Clin Immunol. 2021;41(5):881-895. doi:10.1007/s10875-021-01059-7

Gupton SE, McCarthy EA, Markert ML. Care of children with DiGeorge before and after cultured thymus tissue implantation. J Clin Immunol. 2021;41:896-905. https://pubmed.ncbi.nlm.nih.gov/34003433/

Amatuni GS, Currier RJ, Church JA, Bishop T, Grimbacher E, Nguyen AA, Agarwal-Hashmi R, Aznar CP, Butte MJ, Cowan MJ, Dorsey MJ, Dvorak CC, Kapoor N, Kohn DB, Markert ML, Moore TB, Naides SJ, Sciortino S, Feuchtbaum L, Koupaei RA, Puck JM. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California, 2010-2017. Pediatrics. 2019;143:e20182300. https://www.ncbi.nlm.nih.gov/pubmed/30683812

Hasegawa, K., Tanaka H, Higuchi Y, Hayashi Y, Kobayashi K, Tsukahara H. Novel heterozygous mutation in TBX1 in an infant with hypocalcemic seizures. Clin Pediatr Endocrinol. 2018;27:159-164. https://pubmed.ncbi.nlm.nih.gov/30083032/

Liu, N., Shoch K, Luo X, Pena LDM, Bhavana VH, Kukolich MK, Stringer S, Powis Z, Radtke K, Mroske C, Deak K, McDonald MR, McConkie-Rosell A, Markert ML, Kranz PG, Stong N, Need AC, Bick D, Amaral MD, Worthey EA, Levy S, Undiagnosed Diseases Network (UDN), Wangler M, Bellen HJ, Shashi V, Yamamoto S. Functional variants in TBX2 are associated with a syndromic cardiovascular and skeletal developmental disorder. Hum Mol Genet. 2018;27:2454-2465. https://pubmed.ncbi.nlm.nih.gov/29726930/

Davies EG, Cheung M, Gilmour K, Maimaris J, Curry J, Furmanski A, Sebire N, Halliday N, Mengrelis K, Adams S, Bernatoniene J, Bremner R, Browning M, Devlin B, Erichsen HC, Gaspar HB, Hutchison L, Winnie Ip, Ifversen M, Leahy TR, McCarthy E, Moshous D, Neuling K, Pac M, Papadopol A, Parsley K, Poliani L, Ricciardelli, Sansom DM, Voor T, Worth A, Crompton T, Markert ML, Thrasher A.. Thymus transplantation for complete DiGeorge syndrome: European experience. J Allergy Clin Immunol. 2017;140:1660-1670. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716670/

Dornemann R, Koch R, Mollmann U, et al. Fetal thymus size in pregnant women with diabetic diseases. J Perinatal Med. 2017;45:595-601. https://www.ncbi.nlm.nih.gov/pubmed/28195554

Paganini I, Sestini R, Capone GL, Putignano AL, Contini E, Giotti I, Gensini F, Marozza A, Barilaro A, Porfirio B, Papi L. A novel PAX1 null homozygous mutation in autosomal recessive otofaciocervical syndrome associated with severe combined immunodeficiency. Clin Genet. 2017;92:664-668. https://pubmed.ncbi.nlm.nih.gov/28657137/

Rota IA, Dhalla F. FOXN1 deficient nude severe combined immunodeficiency. Orphanet J Rare Dis. 2017;12(1):6. Published 2017 Jan 11. doi:10.1186/s13023-016-0557-1

Stone CA Jr, Markert ML, Abraham RS, Norton A. A case of atypical, complete DiGeorge syndrome without 22q11 mutation. Ann Allergy Asthma Immunol. 2017;118:640-642. https://www.ncbi.nlm.nih.gov/pubmed/28477796

Warncke K, Lickert T, Eitel S, Gloning K-P, Bonifacio E, Sedlmeier E-M, Becker P, Knoop J, Beyerlein A, Ziegler A-G. Thymus growth and fetal immune response in diabetic pregnancies. Horm Metab Res. 2017;49:892- 898. https://www.ncbi.nlm.nih.gov/pubmed/29136677

Warncke K, Lickert T, Eitel S, Gloning K-P, Bonifacio E, Sedlmeier E-M, Becker P, Wong MT, Scholvinck EH, Lambeck AJ, van Ravenswaaij-Arts CM. CHARGE syndrome: a review of the immunological aspects. Eur J Hum Genet. 2015;23:1451-1419. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4613462/

Lee JH, Markert ML, Hornik CP, McCarthy EA, Gupton SE, Cheifetz IM, Turner DA. Clinical course and outcome predictors of critically ill infants with complete DiGeorge anomaly following thymus transplantation. Pediatr Crit Care Med. 2014;15:e321-326. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156516/

Davies, EG. Immunodeficiency in DiGeorge syndrome and options for treating cases with complete athymia. Front Immunol. 2013;4:322. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3814041/

Kobayashi D, Sallaam S, Humes RA. Tetralogy of Fallot with complete DiGeorge syndrome: report of a case and a review of the literature. Congenit Heart Dis. 2013;8:E119-126. https://www.ncbi.nlm.nih.gov/pubmed/22883347

Markert ML, Devlin BH, Chinn IK, McCarthy EA. Thymus transplantation in complete DiGeorge anomaly. Immunol Res. 2009;44:61-70. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951183/

Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE, Chinn IK, Hale LP, Kepler TB, He M, Sarzotti M, Skinner MA, Rice HE, Hoehner JC. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplant. Blood. 2007;109:4539-4547. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885498/

Lalani, S.R., Safiullah AM, Molinari LM, Fernbach SD, Martin DM, Belmont JW. SEMA3E mutation in a patient with CHARGE syndrome. J Med Genet. 2004;41:e94.

Markert ML, Alexieff MJ, Li J, Sarzotti M, Ozaki DA, Devlin BH, Sempowski GD, Rhein ME, Szabolcs P, Hale LP, Buckley RH, Coyne KE, Rice HE, Mahaffey SM, Skinner MA. Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases. J Allergy Clin Immunol. 2004;113:734-741. https://www.jacionline.org/article/S0091-6749(04)00922-4/pdf

Rice HE, Skinner MA, Mahaffey SM, Oldham KT, Ing RJ, Hale LP, Markert ML. Thymic transplantation for complete DiGeorge syndrome: medical and surgical considerations. J Pediatr Surg. 2004;39:1607-1615. https://www.ncbi.nlm.nih.gov/pubmed/15547821

Markert ML, Sarzotti M, Ozaki DA, Sempowski GD, Rhein ME, Hale LP, Le Deist F, Alexieff MJ, Li J, Hauser ER, Hynes BF, Rice HE, Skinner MA, Mahaffey SM, Jaggers J, Stein LD, Mill MR. Thymus transplantation in complete DiGeorge syndrome: immunologic and safety evaluations in 12 patients. Blood. 2003;102:1121-1130. https://www.bloodjournal.org/content/102/3/1121?sso-checked=true

Yagi H, Furutani Y, Hamada H, Sasaki T, Asakawa S, Minoshima S, Ichida F, Joo K, Kimura M, Imamura S-I, Kamatani N, Momma K, Tako A, Nakazawa M, Shimizu N, Matsuoka R. Role of TBX1 in human del22q11.2 syndrome. Lancet. 2003;362:1366-73. https://pubmed.ncbi.nlm.nih.gov/14585638/

INTERNET

Lackey AE, Muzio MR. DiGeorge Syndrome. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549798/ Accessed Dec 5, 2023.

T-cell immunodeficiency with thymic aplasia. Orphanet. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=83471#:~:text=A%20rare%20primary%20immunodeficiency%20with,levels%20are%20normal%20or%20increased. Accessed Dec 5, 2023.

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Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Patient Organizations

No patient organizations found related to this disease state.


National Organization for Rare Disorders