Rare Pediatrics News

Disease Profile

15q24 microdeletion syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Del(15)(q24); Monosomy 15q24

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 94065

Definition
15q24 microdeletion syndrome is a rare chromosomal anomaly characterized cytogenetically by a 1.7-6.1 Mb deletion in chromosome 15q24 and clinically by preand post-natal growth retardation, intellectual disability, distinct facial features, and genital, skeletal, and digital anomalies.

Epidemiology
The prevalence of 15q24 deletion syndrome is unknown. To date, 19 cases with clinical data and detailed mapping of genomic breakpoints have been reported.

Clinical description
At birth, approximately 1/3 of patients have low birth weight consistent with intrauterine growth retardation. Feeding difficulties and failure to thrive are reported in about 20%. In later childhood, 30% show growth retardation and short stature and 17% obesity. Growth hormone (GH) deficiency may be present. Growth delay, feeding difficulties, and distinct facial features (long face with high anterior hairline, epicanthal folds, hypertelorism, downslanting palpebral fissures, sparse and broad medial eyebrows, broad and/or depressed nasal bridge, long smooth philtrum, and small mouth with full lower lip) are the most common early presenting symptoms. Most patients (90%) have digital deformities (proximally implanted and/or hypoplastic thumbs, clinodactyly, brachydactyly, overriding toes, toe syndactyly, small hands). Approximately 60% have skeletal complications (joint laxity and scoliosis). Hernias are found as well as hypotonia (60%). Eye abnormalities are common (nystagmus and strabismus). Ear abnormalities are variable but common (large ears, ear lobe pits, anteverted ear lobes, and protuberant ears). Genital abnormalities are common in males (60%). Mild to moderate developmental delay is found in all patients. Behavior abnormalities, such as autism, hyperactivity, aggression, and attention deficit are reported in 37%. Approximately 50% of patients have abnormal brain imaging on magnetic resonance imaging (MRI). Nearly 40% have a history of recurrent infections. Recurrent ear infections may be a predisposing factor to hearing loss (25%). Microcephaly is uncommon (20%). Other congenital malformations, while rare, can be severe and include cardiovascular malformations, congenital diaphragmatic hernia, intestinal atresia, imperforate anus, and myelomeningocele (see these terms).

Etiology
The syndrome is caused by a microdeletion of 1.7 to 6.1 Mb in size in chromosome 15q24 which usually results from nonallelic homologous recombination (NAHR). The smallest region of overlap (SRO) spans a 1.2 Mb region including several candidate genes that may predispose to many of the clinical features: CYP11A1, SEMA7A, CPLX3, ARID3B, STRA6, SIN3A and CSK.

Diagnostic methods
Oligonucleotide array CGH (aCGH) with confirmation by fluorescent in-situ hybridization (FISH) detects most, if not all, deletions of 15q24. Karyotypes are typically normal.

Differential diagnosis
Differential diagnoses include other genetic syndromes, particularly monosomy 22q11, Prader-Willi, and Noonan syndromes (see these terms).

Antenatal diagnosis
Deletion of 15q24 can be detected in amniotic fluid or chorionic villi samples. Since routine karyotyping is not sufficient to detect the deletion, aCGH should be performed.

Genetic counseling
The deletion occurred as a de novo event in all reported patients when parents were available for testing. Parental aCGH and/or FISH studies are recommended to provide accurate genetic counseling.

Management and treatment
Management should be multi-disciplinary with the primary care physician and clinical geneticist playing crucial roles in appropriate screening, surveillance, and care. At the time of diagnosis, baseline echocardiograms, audiologic, ophthalmologic, and developmental assessments are needed. Growth and feeding should be monitored closely.

Prognosis
The prognosis is variable and depends on the severity and extent of congenital malformations.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Global developmental delay
0001263
30%-79% of people have these symptoms
Abnormality of the outer ear
Abnormality of the external ear
Ear anomalies
External ear malformations
Outer ear abnormality

[ more ]

0000356
Behavioral abnormality
Behavioral changes
Behavioral disorders
Behavioral disturbances
Behavioral problems
Behavioral/psychiatric abnormalities
Behavioural/Psychiatric abnormality
Psychiatric disorders
Psychiatric disturbances

[ more ]

0000708
Brachydactyly
Short fingers or toes
0001156
Broad eyebrow
Broad eyebrows
Flared eyebrow
Increased vertical height of eyebrow
Increased vertical thickness of eyebrow

[ more ]

0011229
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
High anterior hairline
High frontal hairline
0009890
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

0001388
Long philtrum
0000343
Muscular hypotonia
Low or weak muscle tone
0001252
Postnatal growth retardation
Growth delay as children
0008897
Recurrent infections
Frequent infections
Frequent, severe infections
Increased frequency of infection
infections, recurrent
Predisposition to infections
Susceptibility to infection

[ more ]

0002719
Short stature
Decreased body height
Small stature

[ more ]

0004322
Small for gestational age
Birth weight less than 10th percentile
Low birth weight

[ more ]

0001518
Smooth philtrum
0000319
5%-29% of people have these symptoms
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect

[ more ]

0001627
Abnormal palate morphology
Abnormality of the palate
Abnormality of the roof of the mouth

[ more ]

0000174
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality

[ more ]

0000164
Abnormality of toe
Abnormalities of the toes
0001780
Anal atresia
Absent anus
0002023
Clinodactyly
Permanent curving of the finger
0030084
Coloboma
Notched pupil
0000589
Congenital diaphragmatic hernia
0000776
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Facial asymmetry
Asymmetry of face
Crooked face
Unsymmetrical face

[ more ]

0000324
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Growth hormone deficiency
0000824
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypospadias
0000047
Intestinal atresia
0011100
Kyphosis
Hunched back
Round back

[ more ]

0002808
Long face
Elongation of face
Increased height of face
Increased length of face
Vertical elongation of face
Vertical enlargement of face
Vertical overgrowth of face

[ more ]

0000276
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Microphallus
0030260
Narrow mouth
Small mouth
0000160
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Obesity
Having too much body fat
0001513
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge

[ more ]

0000426
Proximal placement of thumb
Attachment of thumb close to wrist
0009623
Scoliosis
0002650
Seizure
0001250
Small hand
Disproportionately small hands
0200055
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip

[ more ]

0000179
Wide nasal base
Broad base of nose
Broad nasal base
Increased width of base of nose
Increased width of nasal base
Wide base of nose

[ more ]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Learn more

    These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

    Where to Start

    • Genetics Home Reference (GHR) contains information on 15q24 microdeletion syndrome. This website is maintained by the National Library of Medicine.
    • Unique is a source of information and support for families and individuals affected by rare chromosome disorders. Click on the link to view information about 15q24 microdeletion syndrome.

      In-Depth Information

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

        Rare Pediatrics News