RAPADILINO syndrome

Rapadilino syndrome
Other names: Radial and patellar aplasia, Radial and patellar hypoplasia,Absent thumbs, dislocated joints, long face with narrow palpebral fissures, long slender nose, arched palate[1]
Rapadilino syndrome has an autosomal recessive pattern of inheritance.
SpecialtyMusculoskeletal
SymptomsUnderdevelopment or absences of the bones in the forearms, thumbs, and kneecaps, cleft pallet or high-arched, palate, diarrhea, and short stature.
Usual onsetInfancy[2]
DurationLifelong
CausesMutations in the RECQL4 gene[3]
FrequencyLess than 1,000 known cases in the United States[2]

RAPADILINO syndrome is an autosomal recessive disorder characterized by:[4]

It is more prevalent in Finland than elsewhere in the world.[5] It has been associated with the gene RECQL4.[5] This is also associated with Rothmund–Thomson syndrome[6] and Baller–Gerold syndrome.[7]

Signs and symptoms

Most people with RAPADILINO syndrome have underdeveloped or absent bones in the forearms and thumbs. Kneecaps may be underdeveloped or absent. Other characteristics include a cleft or high-arched palate, a long, narrow nose, and dislocated joints.[3]

Many infants with RAPADILINO suffer feeding difficulties, as well as diarrhea and vomiting. A combination of poor bone development and nutritional deficiencies can cause slow growth and short stature.[3]

Some RAPADILINO syndrome patients have harmless light brown patches of skin that resemble café-au-lait spots. Patients with RAPADILINO syndrome are more likely to develop osteosarcoma or lymphoma. In those with RAPADILINO syndrome, osteosarcoma typically develops during childhood or adolescence, whereas lymphoma develops in early adulthood.[3]

Cause

RAPADILINO syndrome is caused by RECQL4 gene mutations. The RECQL4 gene gives instructions to produce a member of a protein family known as RecQ helicases. Helicases are enzymes that temporarily bind to DNA and unwind the DNA molecule's two spiral strands. This unwinding is needed for DNA replication to prepare for cell division and for mending damaged DNA. The RECQL4 protein is involved in DNA replication and repair as well as the stability of genetic information in cells.[3]

The most frequent RECQL4 gene mutation linked to RAPADILINO syndrome causes the RECQL4 protein to be misassembled. This genetic mutation causes the formation of a protein that lacks exon 7, therefore cannot function as a helicase. In the lack of helicase function, normal DNA replication and repair may be impaired resulting in widespread genetic damage. Although it is unknown how RECQL4 gene mutations produce RAPADILINO syndrome's specific symptoms, these changes may result in the accumulation of DNA errors and cell death.[3]

Diagnosis

CT scan showing mediastinal enlargement and bilateral infiltrates.

Differential diagnosis

The DDx is based on the following:[8]

Treatment

The management of RAPADILINO syndrome is done via nutritional and orthopedic means[8]

References

  1. ↑ "GARD Rare Disease Information - Rapadilino syndrome - National Organization for Rare Disorders". rarediseases.org. 16 June 2022. Archived from the original on 13 May 2022. Retrieved 22 July 2023.
  2. 1 2 "RAPADILINO syndrome - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Archived from the original on 30 June 2023. Retrieved 18 July 2023.
  3. 1 2 3 4 5 6 "RAPADILINO syndrome". medlineplus.gov. Archived from the original on 19 July 2023. Retrieved 18 July 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  4. ↑ 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.
  5. 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.
  6. ↑ 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.
  7. ↑ Online Mendelian Inheritance in Man (OMIM): 218600
  8. 1 2 RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: RAPADILINO syndrome". www.orpha.net. Archived from the original on 19 July 2023. Retrieved 22 July 2023.
Classification
External resources


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