Plain-language definitions of terms found in SETD5 Syndrome reports, appointments, and research. Not medical advice.
These definitions are intended to help you understand terms you may encounter in reports and appointments -- not to replace guidance from your medical team. Each entry includes a plain-language definition and, where relevant, a brief note on where the term has appeared in SETD5-related research or reports. Terminology and testing methods can vary by laboratory and country.
Companion reference
A plan under Section 504 of the Rehabilitation Act providing accommodations to support access to education for a student with a disability. A 504 plan typically addresses accommodations rather than specialized instruction.
A chromosomal condition caused by a deletion of genetic material at position 25.3 on the short arm (p) of chromosome 3. This region includes the SETD5 gene, and reduced SETD5 dosage (haploinsufficiency) is considered a key contributor to the associated features.
Communication methods that supplement or replace spoken language. AAC includes high-tech tools (speech-generating devices, tablet apps), low-tech tools (picture boards), and manual systems (sign language, gestures).
A professional organization that publishes guidelines broadly adopted for classifying genetic variants. The five-tier system (benign, likely benign, uncertain significance, likely pathogenic, pathogenic) is the framework most commonly used by clinical genetics laboratories in the US when reporting results.
A neurodevelopmental diagnosis involving persistent patterns of inattention and/or hyperactivity-impulsivity that interfere with functioning or development. Presentations are commonly categorized as predominantly inattentive, predominantly hyperactive-impulsive, or combined.
A congenital heart defect involving a combined opening between chambers and abnormal development of atrioventricular valves. Severity varies and management may include surgical repair depending on anatomy and symptoms.
A neurodevelopmental diagnosis characterized by differences in social communication and interaction, along with restricted or repetitive patterns of behavior, interests, or activities. Diagnosis is based on developmental history and behavioral assessment.
An inheritance pattern in which having one altered copy of a gene (out of the usual two) is sufficient to cause a condition. "Autosomal" means the gene is located on one of the 22 non-sex chromosomes. A person with an autosomal dominant condition has a 50% chance of passing the variant to each child.
Abnormally short fingers or toes caused by shortening of the bones in the digits. It can occur as an isolated finding or as part of a broader syndrome involving skeletal anomalies.
A head shape in which the back of the skull is flatter than typical, resulting in a shorter front-to-back length relative to width. It can be present at birth or develop in infancy. Head circumference is monitored as a routine part of well-child care.
A test designed to detect extra or missing chromosomal material (duplications and deletions). CMA generally does not detect most single-base variants.
A DNA-containing structure in cells that carries genes. Humans typically have 46 chromosomes (23 pairs). Each chromosome has a short arm ("p") and a long arm ("q").
An opening or gap in the roof of the mouth (palate) that occurs when the palatal tissues do not fully fuse during early fetal development. A cleft may involve only the soft palate, extend to the hard palate, or occur alongside a cleft lip. It can affect feeding, speech, and hearing and is typically managed surgically.
A structural difference in the heart present at birth. Congenital heart defects range from mild to complex and may be detected prenatally or after birth.
A type of genetic variant in which a segment of DNA is deleted (fewer copies than expected) or duplicated (extra copies) compared to the typical two. CNVs can range in size from a few genes to large chromosomal regions. Most whole exome sequencing reports include CNV analysis alongside single-nucleotide variant analysis.
One or both testes have not descended into the scrotum by birth or early infancy. Management is determined by pediatric urology and may include surgery.
A variant that is present in a child but not detected in either parent's tested sample (often blood or saliva). De novo variants typically arise during egg or sperm formation or early embryonic development. Parental testing (trio sequencing) is the standard way to confirm de novo status. Genetic counselors note that while negative parental testing strongly supports de novo status, the possibility of germline mosaicism cannot be completely eliminated. Discuss recurrence risk with your genetic counselor
Loss of a segment of DNA. A deletion may involve a small number of DNA bases within a gene or a larger chromosomal region that includes multiple genes.
A clinical description indicating that the bridge of the nose (the area between the eyes) appears lower or flatter than typical. It is a common dysmorphic feature noted on physical examination and does not typically require treatment on its own.
A term used in rare disease contexts to describe a prolonged process of seeking a diagnosis, often involving multiple evaluations and tests over time.
Services provided under Part C of IDEA for infants and toddlers (birth to age 3) with developmental delays or disabilities. Services and eligibility criteria are state-administered in the U.S. and can include therapy and developmental supports.
A non-invasive test that records electrical activity of the brain using sensors placed on the scalp. EEG findings can support evaluation of seizures and other neurological concerns.
Incomplete or deficient formation of tooth enamel, resulting in enamel that is thinner, softer, or pitted compared to typical. It can affect primary (baby) or permanent teeth and may increase sensitivity and risk of cavities. Regular dental check-ups are commonly part of care for children with this finding.
A neurological condition defined by recurrent unprovoked seizures. Seizures can vary in presentation, including convulsive events, brief lapses in awareness, involuntary movements, or sensory symptoms.
Molecular processes that influence gene activity without altering the underlying DNA sequence. Examples include chemical modifications of DNA and histones and changes to chromatin structure.
Expressive language refers to communicating thoughts or needs (spoken words, sign, writing, or device-based communication). Receptive language refers to understanding language (following directions, comprehending speech, processing meaning). These skills can develop at different rates within the same person.
A legal right under IDEA requiring public schools to provide eligible students with disabilities special education and related services at no cost, designed to meet the student's unique needs.
A descriptive term for inadequate weight gain or growth pattern compared with expected trajectories. It is not a single diagnosis; evaluation focuses on identifying underlying causes such as feeding difficulty, medical conditions, or nutritional issues.
A mutation caused by inserting or deleting a small number of DNA letters, shifting the "reading frame" (the way a cell interprets genetic code). This frequently disrupts the downstream protein sequence, typically resulting in a truncated, non-functional protein or triggering nonsense-mediated decay (the cell's mechanism for destroying faulty messages).
Backflow of stomach contents into the esophagus. Reflux can be physiologic in infancy; GERD is typically used when reflux is associated with symptoms or complications such as feeding difficulty or poor growth.
A segment of DNA that contains information used to make a functional product, commonly a protein. Humans typically have two copies of most genes, one inherited from each parent.
A healthcare professional trained to explain genetic test results, discuss inheritance and recurrence risk, and support decision-making related to genetic conditions.
A situation where a genetic variant is present in a subset of a parent's egg or sperm cells but may be absent (or present at very low levels) in blood or saliva. This can affect recurrence risk even when parental blood testing is negative.
A descriptive term used when a child (typically under age five) shows significant delay in two or more developmental domains such as motor, language, cognitive, social, or daily living skills.
A large public database that aggregates DNA sequencing data from hundreds of thousands of people across diverse ancestries. Clinical labs check gnomAD to determine how frequently a variant appears in the general population; variants that are absent or very rare in gnomAD are more likely to be disease-causing.
Gross motor refers to large-muscle movements (sitting, walking, running). Fine motor refers to small-muscle movements (grasping objects, drawing, handwriting, using utensils).
A genetic mechanism in which a single functional copy of a gene does not produce enough gene product for typical function, so reduced dosage can contribute to a condition.
Having one copy of a gene variant and one unaffected copy. In autosomal dominant conditions, a single heterozygous variant is typically sufficient to cause the condition. Lab reports list "zygosity" to indicate whether one or both gene copies carry the variant.
A palate (roof of the mouth) that is narrower and more steeply arched than typical. It can be associated with feeding, dental, or speech considerations in some individuals.
Proteins around which DNA is wrapped to form chromatin. Chemical modifications to histones can influence how accessible DNA is for gene expression.
An increased distance between the eyes, measured using standard clinical landmarks. The term is descriptive and can be present in many conditions.
Blood glucose level below expected range. Symptoms can vary by age and severity and can include irritability, sweating, shakiness, lethargy, or seizures in severe cases. Evaluation and management depend on clinical context.
Reduced muscle tone, meaning decreased resistance to passive movement when muscles are at rest. Hypotonia can affect posture and motor development and may be associated with feeding or speech-motor difficulties.
A condition where the urethral opening is located on the underside of the penis rather than at the tip. Severity varies. Management may include surgical repair depending on anatomy and function.
A written plan under the Individuals with Disabilities Education Act (IDEA) for an eligible student, describing special education services, goals, and accommodations. The IEP is developed and reviewed by a team that includes parents/guardians and school staff.
Protrusion of tissue (often intestine) through a weak area in the lower abdominal wall into the groin. In children, inguinal hernias are commonly treated surgically.
A diagnosis characterized by limitations in intellectual functioning (such as reasoning, learning, and problem-solving) and adaptive behavior (everyday practical and social skills), with onset during the developmental period. Severity levels are commonly described as mild, moderate, severe, or profound based on functional assessment.
Increased joint range of motion due to connective tissue characteristics. Joint laxity can be associated with sprains, joint pain, fatigue with activity, or fine motor challenges in some individuals.
A rare genetic condition caused by variants in the ANKRD11 gene, characterized by intellectual disability, short stature, distinctive facial features (including widely spaced teeth and broad eyebrows), behavioral differences, and skeletal anomalies. Named using the initials of the first three families described.
An excessive outward curvature of the upper spine, causing the back to appear rounded. Mild kyphosis is common, but pronounced kyphosis may be monitored or managed by an orthopedic specialist depending on severity and progression.
A requirement under IDEA that students with disabilities are educated with nondisabled peers to the maximum extent appropriate, with placement determined by the IEP team based on the student's needs.
A type of genetic variant (including nonsense, frameshift, or splice site changes) that significantly reduces or eliminates normal gene function. Loss-of-function variants are common disease mechanisms in autosomal dominant conditions where one working copy of the gene is insufficient.
Head circumference significantly below average for age and sex, typically defined as more than two standard deviations below the mean. Microcephaly can be present at birth or develop over time.
A smaller than typical lower jaw (mandible). Micrognathia can affect feeding, dental alignment, and in some cases breathing. It may be noted by a dysmorphologist, pediatric dentist, or craniofacial specialist.
A rare cerebrovascular disorder involving progressive narrowing of certain brain arteries and development of small collateral vessels visible on imaging. It can be associated with ischemic events or hemorrhage and is evaluated by specialists.
A historical OMIM designation used in some databases for the condition associated with SETD5 loss of function. OMIM terminology may not reflect current clinical language.
A normal cellular process that detects and destroys messenger RNA (mRNA) molecules containing premature "stop" signals. When a frameshift or nonsense mutation creates an early stop codon, NMD often degrades the faulty mRNA before a harmful, truncated protein can be made, effectively silencing the altered gene copy.
Repetitive involuntary movements of the eyes (horizontal, vertical, or rotary). Nystagmus can affect vision and is evaluated by ophthalmology and, when indicated, neurology.
Clinical services focused on functional participation in daily activities. In pediatrics, OT may address fine motor skills, self-care tasks, play skills, sensory processing supports, handwriting, and adaptive strategies.
The opening between the upper and lower eyelids. Clinicians may describe palpebral fissures as upslanting (angled upward from inner to outer corner) or downslanting (angled downward), which can be a distinguishing craniofacial feature in certain syndromes.
A classification indicating that evidence supports a variant as disease-causing (pathogenic) or strongly suggests it is disease-causing (likely pathogenic). Laboratories commonly use a five-tier system: benign, likely benign, uncertain significance (VUS), likely pathogenic, and pathogenic.
A structured database that collects information about individuals with a condition for research purposes (for example, medical history, symptoms, genetics, and outcomes). Registries are typically voluntary and governed by research protocols.
The observable characteristics of an individual (including physical features, medical conditions, behaviors, and developmental profile) resulting from the interaction of genes and environment. Genetic testing reports describe the individual's phenotype to guide interpretation of variants.
The vertical groove between the nose and upper lip. Clinical notes may describe the philtrum as long or smooth based on appearance.
Clinical services focused on movement, strength, balance, coordination, flexibility, and functional mobility. PT may address gross motor skills and gait patterns.
Presence of an additional finger or toe. The extra digit can range from a small soft-tissue appendage to a fully formed digit. Polydactyly may be preaxial (thumb/big-toe side) or postaxial (pinky-toe side).
The family member whose symptoms prompted genetic testing and from whom the analysis begins. Genetic reports are written from the proband's perspective, and parental samples are tested separately to determine whether a variant is inherited or de novo.
A broad or webbed appearance of the neck caused by extra skin or soft tissue extending from the neck toward the shoulders. It can range from a subtle tightness to a visible skin fold and may be associated with underlying structural differences.
Drooping of the upper eyelid. In some cases, ptosis can affect vision development and may be treated medically or surgically.
The probability that a genetic condition will occur again in a future pregnancy. Recurrence risk depends on inheritance pattern, parental testing results, and other factors assessed by genetics professionals.
Bone density below expected levels for age. Reduced bone mineral density can increase risk of fracture and may be evaluated using imaging such as a DEXA scan when clinically indicated.
Small indentations or pits in the skin located behind or near the ear, formed during fetal development when ear tissue fuses. They are usually harmless but can occasionally be associated with a syndrome or, in some cases, with hearing differences.
A lateral curvature of the spine. Management can include monitoring, bracing, physical therapy, or surgery depending on severity and progression.
A gene that provides instructions for making the SETD5 protein. SETD5 is a chromatin regulator that helps control gene activity, often by working with other proteins that modify histones. It is particularly important during brain development. Haploinsufficiency of SETD5 (having only one functional copy) is the primary disease mechanism. Researchers continue to study the exact biochemical details of how SETD5 functions.
Differences in how the nervous system detects, interprets, and responds to sensory input such as sound, touch, texture, light, or movement. Individuals may be over-responsive, under-responsive, or seek specific sensations.
A change affecting a single DNA base (A, C, G, or T) at a specific position. Depending on location and effect, an SNV can be benign or can alter gene function.
Disruptions in the flow of speech such as repetitions, prolongations, or pauses. Dysfluency can have multiple causes and is evaluated by speech-language pathologists.
Clinical services addressing communication and language. Depending on clinical needs, SLP can include speech sound production, vocabulary, sentence development, pragmatic language, comprehension, and in some settings feeding and swallowing evaluation.
A condition where the eyes do not align in the same direction at the same time. Types include inward turning (esotropia) or outward turning (exotropia). Management may include glasses, patching, medications, or surgery depending on cause and severity.
A condition in which two or more fingers or toes are joined together by skin or bone. It ranges from mild webbing to complete fusion and may involve the hands, feet, or both. Some forms are isolated; others occur as part of a broader syndrome.
Eyebrows that meet in the middle or nearly meet across the bridge of the nose.
A descriptive term for a facial shape that is broader at the forehead/temples and narrower at the chin.
Sequencing performed on the child and both parents, analyzed together. Trio analysis can help determine whether a variant is inherited or de novo and can improve interpretation.
A pattern where performance differs across cognitive domains (for example, stronger skills in one area and weaker skills in another) on standardized assessment.
A difference in DNA sequence compared with a reference sequence. Variants can be benign, uncertain, or disease-causing depending on available evidence.
A classification indicating that current evidence is insufficient to determine whether a variant is disease-causing or benign. VUS classifications can change over time as additional evidence becomes available.
Structural differences in the bones of the spine (vertebrae), which may include variations in shape, number, size, or fusion. Depending on location and severity, vertebral anomalies may be asymptomatic or may affect posture, movement, and spinal cord function.
A genetic test that sequences most protein-coding regions of genes (exons). WES can identify many sequence variants, including missense, nonsense, frameshift, and small insertions/deletions. Reports typically include quality metrics such as mean depth of coverage (how many times each region was sequenced) and the percentage of the target covered at adequate depth. Most labs also perform CNV analysis on the same data to detect deletions and duplications of three or more exons.
The ability to hold and manipulate information over short periods, such as following multi-step instructions or performing mental arithmetic.