RAPADILINO syndrome

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Rapadilino syndrome
Other namesRadial and patellar aplasia, Radial and patellar hypoplasia
Autorecessive.svg
Rapadilino syndrome has an autosomal recessive pattern of inheritance.
Specialty Musculoskeletal
Symptoms Underdevelopment or absences of the bones in the forearms, thumbs, and kneecaps, cleft pallet or high-arched, palate, diarrhea, and short stature.
Usual onsetInfancy [1]
DurationLifelong
CausesMutations in the RECQL4 gene [2]
FrequencyLess than 1,000 known cases in the United States [1]

RAPADILINO syndrome is an autosomal recessive disorder characterized by: [3]

Contents

It is more prevalent in Finland than elsewhere in the world. [4] It has been associated with the gene RECQL4. [4] This is also associated with Rothmund–Thomson syndrome [5] and Baller–Gerold syndrome. [6]

Signs and symptoms

The majority of those affected have radial ray abnormalities, which are underdevelopment or absences of the bones in the forearms and thumbs. Kneecaps (patellae) may be underdeveloped or missing. Other characteristics include an opening in the roof of the mouth (cleft palate) or a high-arched palate; a long, slender nose; and dislocated joints. [2]

Many infants with RAPADILINO syndrome suffer feeding difficulties, as well as diarrhea and vomiting. Slow growth and short stature result from the combination of defective bone development and nutrition issues in affected individuals. [2]

Some people with RAPADILINO syndrome have harmless light brown patches of skin which resemble café-au-lait spots. Patients with RAPADILINO syndrome have a slightly higher chance of getting osteosarcoma or lymphoma. Osteosarcoma most commonly occurs during infancy or adolescence in RAPADILINO syndrome patients, while lymphoma develops in early adulthood. [2]

Cause

RAPADILINO syndrome is caused by mutations in the RECQL4 gene. The RECQL4 gene provides instructions for making one member of a protein family called RecQ helicases. Helicases are enzymes that bind to DNA and temporarily unwind the DNA molecule's two spiral strands (double helix). This unwinding is required for DNA replication (copying) in preparation for cell division and for mending damaged DNA. The RECQL4 protein aids in the stabilization of genetic information in cells and is involved in DNA replication and repair. [2]

The most common RECQL4 gene mutation associated with RAPADILINO syndrome causes the RECQL4 protein to be pieced together improperly. This genetic mutation causes the creation of a protein that lacks exon 7 and hence cannot function as a helicase. The absence of helicase function may inhibit normal DNA replication and repair, resulting in widespread genetic damage over time. Although it is unclear how RECQL4 gene mutations cause the specific symptoms of RAPADILINO syndrome, these changes may result in the accumulation of DNA mistakes and cell death. [2]

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References

  1. 1 2 "RAPADILINO syndrome - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 18 July 2023.
  2. 1 2 3 4 5 6 "RAPADILINO syndrome". medlineplus.gov. Retrieved 18 July 2023.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  3. Kaariainen H, Ryoppy S, Norio R (1989). "Rapadlino syndrome with radial and patellar aplasia/hypoplasia as main manifestations". Am J Med Genet. 33 (3): 346–351. doi:10.1002/ajmg.1320330312. PMID   2801769.
  4. 1 2 Siitonen HA, Kopra O, Kääriäinen H, et al. (November 2003). "Molecular defect of RAPADILINO syndrome expands the phenotype spectrum of RECQL diseases". Hum. Mol. Genet. 12 (21): 2837–44. doi: 10.1093/hmg/ddg306 . PMID   12952869.
  5. Yin J, Kwon YT, Varshavsky A, Wang W (October 2004). "RECQL4, mutated in the Rothmund-Thomson and RAPADILINO syndromes, interacts with ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway". Hum. Mol. Genet. 13 (20): 2421–30. doi: 10.1093/hmg/ddh269 . PMID   15317757.
  6. Online Mendelian Inheritance in Man (OMIM): 218600