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Introduction
3q29 deletion syndrome is a rare genetic disorder caused by the deletion of a specific segment of chromosome 3. Symptoms of this syndrome vary widely: while mild to moderate developmental delay and intellectual disability are commonly observed, some individuals may show no obvious symptoms at all. The condition is usually diagnosed through genetic testing. The main features include delayed speech and global developmental delay, along with distinctive facial characteristics. These may include a long, narrow face, microcephaly (small head), short philtrum, high nasal bridge, and large, posteriorly rotated ears. In infancy, growth failure and feeding difficulties are common, along with hypotonia (low muscle tone) and frequent ear infections. Some children present with congenital heart defects (the most common being patent ductus arteriosus), and rare congenital anomalies such as horseshoe kidney or hypospadias. There is also an increased risk of neurodevelopmental and psychiatric disorders, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), bipolar disorder, and schizophrenia. The deleted chromosomal region contains about 20 genes, many of which are thought to play roles in brain development. However, the precise mechanisms by which these deletions lead to clinical symptoms, and why some individuals remain asymptomatic, are still not fully understood. Children with this syndrome often experience challenges in adaptive behavior, which refers to everyday life skills such as communication, household tasks, money management, and personal care. Research suggests that executive functioning (e.g., goal-setting, problem-solving) may have a stronger influence on adaptive behavior than general cognitive ability. In many cases, expressive communication is relatively strong, whereas difficulties are more often seen in writing skills, social relationships, and coping with stress. Daily living skills are often below average, although variability among individuals is high. From a physical health perspective, heart disease and gastrointestinal problems are frequently reported. About 25% of patients have heart issues, and gastrointestinal symptoms such as gastroesophageal reflux and constipation are also very common. Frequent ear infections and hearing loss may further contribute to speech delay. Early intervention and comprehensive care are very important for children with 3q29 deletion syndrome. Occupational therapy, educational support, and training aimed at improving executive function are effective. Regular psychiatric evaluation and tailored treatment planning are also recommended. Although the impact of the syndrome varies greatly between individuals, ongoing research is expected to improve understanding and lead to better support strategies. If a child is diagnosed with this condition, working closely with healthcare professionals to develop individualized support is essential.
[1] FGF12 – Hereditary Ataxia and Brugada Syndrome
Hereditary Ataxia is a neurological disorder caused by dysfunction of the cerebellum, the brain region that regulates movement, posture, and balance. Genetic degeneration of the cerebellum and spinal cord leads to progressive symptoms such as:
Unsteady, slow gait with frequent falls
Vertigo or balance loss
Poor coordination of hands and fingers, tremor
Slurred or unclear speech, choking
Rarely, diplopia (double vision)
Symptoms may worsen with fatigue or alcohol intake, but over time they become persistent and disabling. Neurological examinations often reveal typical cerebellar signs: wide-based unsteady gait, trunk instability even while seated, and impaired fine motor control (dysmetria).
Diagnosis relies on brain imaging such as MRI or MRS, often showing cerebellar atrophy. As the disease progresses, patients may require mobility aids or wheelchairs, and face complications such as falls, aspiration, or loss of independence.
Treatment is supportive rather than curative. Physiotherapy helps maintain motor function, and medications can reduce tremor or spasticity. Genetic counseling is essential for families, aiding in disease understanding and daily life planning.
Brugada Syndrome is a heart condition caused by abnormal electrical conduction. It is characterized by distinctive ECG findings, especially ST-segment abnormalities in leads V1–V3. Brugada syndrome is associated with life-threatening ventricular arrhythmias and sudden cardiac death, with an average age of onset around 40 years. Cases may occur in infancy or childhood, especially with a positive family history.
Diagnosis is based on ECG features, clinical history, and family history. Molecular diagnosis can confirm pathogenic variants, particularly in genes such as SCN5A.
Treatment includes implantation of an implantable cardioverter defibrillator (ICD) for patients with prior cardiac arrest or syncope. Isoproterenol is used for electrical storm (multiple arrhythmias). Patients should avoid triggers such as certain drugs (e.g., tricyclic antidepressants, some antiarrhythmics), cocaine, and high fever.
FGF12 encodes a fibroblast growth factor that interacts with sodium channels (NaV), regulating cellular excitability. Mutations have also been linked to developmental and epileptic encephalopathy (DEE47), childhood-onset epilepsy, intellectual disability, and microcephaly.
Both hereditary ataxia and Brugada syndrome impose significant psychological and physical burdens on patients and families, making medical and psychological support critical.
[2] RPL35A – Diamond-Blackfan Anemia (DBA5)
Diamond-Blackfan anemia type 5 (DBA5) is a rare disorder caused by mutations in the RPL35A gene, located in the 3q29 region. RPL35A encodes ribosomal protein eL33, a component of the large ribosomal subunit, essential for protein synthesis and particularly critical for the survival and proliferation of hematopoietic cells.
Defects in RPL35A impair rRNA processing and ribosome maturation, leading to reduced protein synthesis, decreased cell proliferation, and increased apoptosis—especially in hematopoietic progenitors, directly contributing to DBA5.
DBA is classified as a congenital hypoplastic anemia. It typically presents in infancy with moderate to severe macrocytic anemia and reduced erythroid precursors in bone marrow. About 30–40% of patients also have growth retardation or congenital anomalies such as craniofacial malformations (e.g., Pierre Robin sequence, cleft palate), limb abnormalities, or urogenital defects.
Over 90% of cases present before age 1, but clinical severity varies widely. Some patients show only mild anemia, while severe cases can lead to non-immune hydrops fetalis in utero. Patients also have an increased risk of malignancies including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and osteosarcoma.
Treatment includes corticosteroids, red blood cell transfusions, and hematopoietic stem cell transplantation (HSCT)—the only curative option for hematologic manifestations. However, steroid therapy has side effects (infection risk, bone density loss, growth suppression), and long-term transfusions cause iron overload requiring chelation therapy.
Regular monitoring with blood tests, bone marrow exams, and cancer screening is essential. Pregnancy in DBA patients requires close monitoring of maternal hematologic status and fetal development.
DBA prevalence is estimated at 1 in 100,000–200,000 live births, with no significant ethnic differences. Phenotypic variability is high, even within the same family.
Comprehensive, multidisciplinary care is required, involving hematologists, geneticists, oncologists, and supportive therapists, with active family involvement.
Further Reading
Unique (RareChromo): 3q29 deletions and microdeletions (English, with photos)
