NORD gratefully acknowledges Olivia Juarez, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Chromosome 4q deletion is a chromosomal disorder caused by a missing piece of the long arm of chromosome 4. It was first described in 1967 and is linked to symptoms in several organ systems. The patient may have an extremely prominent forehead (frontal bossing), enlargement of the back part of the head, low placement of ears, short broad hands and feet, unusually small size associated with slow or delayed growth, congenital heart defects, and possible intellectual disability.
Patients with chromosome 4q deletion may have the following symptoms: unusual skull shape, short nose with unusual bridge, low-set ears that may not have formed well, cleft in the roof of the mouth, short breastbone, poor or delayed growth, moderate to severe intellectual disability, heart defects, unusual heart rhythm (arrhythmia), defective urinary and reproductive organs (genitourinary defects), small size, small hands and feet, unusually wide-set eyes (hypertelorism), a pointed fifth finger and nail which is common for this disorder, and decreased muscle tone (hypotonia). Some children may have a small jaw (micrognathia) which results in difficulties with breathing. There may be unusual brain findings (corpus callosum). In some patients, slow growth and intellectual disability may be present without obvious physical abnormalities, making it difficult to recognize this disorder.
Some children with chromosome 4q deletion have psychiatric symptoms. These include aggression, hearing speech that is not present (verbal hallucinations), mood swings, and delusions. Not all people with chromosome 4q deletion have these symptoms, and symptoms can vary greatly.
Genetic information, DNA, lies within almost every cell in the body and provides the instructions for how each tissue functions. DNA includes genes, which are responsible for making the proteins that have specific jobs within certain tissues of the body. This DNA is tightly wound and contained within structures called chromosomes. Most people are born with 23 pairs (46 total) of chromosomes in every cell of the body. Each of these 46 chromosomes has a long piece, called arm q, and a short piece, called arm p. Chromosome 4q deletion is caused by a partial missing piece of the long arm of chromosome 4. This chromosome deletion is usually not inherited, but occurs for the first time in the affected person. However, it is possible to pass the deletion to children.
Symptoms can vary greatly, even in members of the same family. The severity and type of symptoms depend on the size and location of the missing chromosomal piece. Whether it is interstitial (situated between other parts of the chromosome) or terminal (on the end part of the chromosome) usually provides information on what to expect. Some genes that might be involved include:
|BMP3||Unusual formation of bones, short stature|
|SEC31A||Facial features or unusual skull shape|
|GRID2, NEUROG2||Seizures, decreased muscle tone, delays in motor development (e.g. sitting, walking)|
|ANK2, HAND2, HPGD, TLL1||Heart issues|
|FGF2||Unusual formation of arms and legs|
Researchers are studying other genes that might be involved with chromosome 4q deletion
Chromosome 4q deletion is a rare disorder that is present at birth and is estimated to occur in 1 out of 100,000 people. Chromosome 4q deletion can sometimes be identified before birth by ultrasound and prenatal chromosome analysis. The condition affects males and females in equal numbers. It is not currently known to affect certain ethnicities more than others. There is typically no family history of the condition, and it occurs randomly.
Chromosome 4q deletion is diagnosed by genetic testing. There are different genetic tests that can be used to find a chromosome 4q deletion. These include:
1. Karyotype – This test makes an image of a person’s chromosomes. This test can be used to find large deletions.
2. FISH (fluorescence in situ hybridization) – This test is used to find a specific DNA region on a chromosome. A chromosome is attached to a small DNA region called a probe that has a glowing (fluorescent) molecule attached to it. This test can be used to find deletions that are too small to be seen on a karyotype. FISH is only useful if the person ordering the test thinks there is a deletion of a specific region of 4q.
3. Array CGH (comparative genomic hybridization) – This test can find deletions that are too small to be seen on a karyotype.
Surgery is used to treat heart and skeletal issues, if needed. Children with delays in walking or other milestones may need treatments like occupational or physical therapy. Children with a small jaw s that makes breathing difficult may require surgery to make the bones longer. Medications may be helpful for seizures, reflux, or growth issues. Special education is helpful for children with intellectual or learning disabilities. Multivitamins and citrus fruits are recommended for all children with chromosome 4q deletion. Coenzyme Q10 can be helpful for people struggling with slow growth and reflux.
For patients of chromosome 4q deletion, special education and vocational services may be of benefit. Early intervention services, such as physical therapy, occupational therapy, and special education are important. Other treatment is based on the symptoms of each person.
Genetic counseling may be of benefit for patients and their families. Genetic counseling involves speaking with a specialized healthcare provider, called a genetic counselor, who collects a detailed personal and family history of the person with chromosome 4q deletion. This can be helpful for determining what therapies and resources might beneficial, as well as who else in the family should consider genetic testing for chromosome 4q deletion. Counselors can also explain the chance of passing down a genetic condition in the family.
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:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/for-patients-and-families/information-resources/info-clinical-trials-and-research-studies/
For information about clinical trials sponsored by private sources, contact: http://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
Pereira ME, Silva RC, Velosa A, Barahona-Correa B. 4q-Deletion Syndrome: Psychiatric Symptoms in a Rare Chromosomal Disorder. Journal of Genetic Syndromes and Gene Therapy. 2016; 7(2). https://www.omicsonline.org/open-access/4q-deletion-syndrome-psychiatric-symptoms-in-a-rare-chromosomal-disorder-2157-7412-1000288.php?aid=69195
Strehle EM, Yu L, Rosenfeld JA, Donkervoort S, Zhou Y, Chen TJ, Martinez JE, Fan YS, Barbouth D, Zhu H, Vaglio A, Smith R, Stevens CA, Curry CJ, Ladda RL, Fan ZJ, Fox JE, Martin JA, Abdel-Hamid HZ, McCracken EA, McGillivray BC, Masser-Frye D, Huang T. Genotype-phenotype analysis of 4q deletion syndrome: proposal of a critical region. American Journal of Medical Genetics. 2012; 158A(9):2139-2151. https://www.ncbi.nlm.nih.gov/pubmed/22847869
Xu W, Ahmad A, Dagenais S, Iyer RK, Innis JW. Chromosome 4q deletion syndrome: narrowing the cardiovascular critical region to 4q32.2-q34.3. American Journal of Medical Genetics A. March 2012; 158A(3):635-640. https://www.ncbi.nlm.nih.gov/pubmed/22302627.
Markiewicz MR, Verschueren D, Assael LA. Chromosome 4q deletion syndrome: craniofacial characteristics associated with monosomy of the long arm of chromosome 4q. Cleft Palate and Craniofacial Journal. September 2010; 47(5):518-522. https://www.ncbi.nlm.nih.gov/pubmed/20170389
Strehle EM, Middlemiss PM. Children with 4q-Syndrome: The Parents’ Perspective. Genetic Counseling. 2007; 18(2): 189-199. https://www.ncbi.nlm.nih.gov/pubmed/17710871
Vogt J, Ryan E, Tischkowitz MD, Reardon W, Brueton LA. The tale of a nail sign in
chromosome 4q34 deletion syndrome. Clinical Dysmorphology. 2006; 15:127-132. https://www.ncbi.nlm.nih.gov/pubmed/16760729
Strehle EM, Bantock HM. The phenotype of patients with 4q-syndrome.
Genetic Counseling. 2003; 14(2):195-205. https://www.ncbi.nlm.nih.gov/pubmed/12872814
Keeling SL, Lee-Jones L, Thopson P. Interstitial Deletion 4q32-34 with Ulnar Deficiency: 4q33 May Be the Critical Region in 4q Terminal Deletion Syndrome. American Journal of Medical Genetics. 2001; 99: 94-98. https://www.ncbi.nlm.nih.gov/pubmed/11241465
Strehle EM, Ahmed OA, Hameed M, Russell A. The 4q-Syndrome. Genetic Counseling. 2001; 12(4) 327-329. https://www.ncbi.nlm.nih.gov/pubmed/11837601
Robertson SP, O’Day K, Bankier A. The 4q-Syndrome: Delineation of the Minimal Critical Region to Within Band 4g31. Clinical Genetics. 1998; 53(1):70-3. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1399-0004.1998.tb02585.x
Suwa A. Momoi MY, Yamagata T, Mori Y. Interstitial Deletion Of The Long Arm of Chromosome 4 [del(4)(q21.22q23)] and a Liver Tumor. American Journal of Medical Genetics. 1998; 78(3):291-93. https://www.ncbi.nlm.nih.gov/pubmed/9677069
Caliebe A, Waltz S, Jenderny J. Mild Phenotypic Manifestations of Terminal Deletion of the Long Arm of Chromosome 4: Clinical Description of a New Patient. Clinical Genetics. 1997; 52:(2):116-119. https://www.ncbi.nlm.nih.gov/pubmed/9298747
Descartes M, Keppler-Noreuil K, Knops J, Longshore JW, Finley WH, Carroll AJ. Terminal Deletion of the Long Arm of Chromosome 4 in a Mother and Two Sons. Clinical Genetics. 1996; 50(6): 538-540. https://www.ncbi.nlm.nih.gov/pubmed/9147894
Copelli S. Brief Clinical Report: Interstitial Deletion of the Long Arm of Chromosome 4,
del(4)(q28–>q31.3). American Journal of Medical Genetics. 1995; 55(1):77-79. https://www.ncbi.nlm.nih.gov/pubmed/7702102
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100