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Rare inherited syndromes

Last updated: October 27, 2021

Summarytoggle arrow icon

This card provides an overview of inherited symptom complexes that occur rarely in the general population. These syndromes are caused by inherited genetic defects, which occur either due to chromosomal aberrations or autosomal/sex-linked traits. The presentation differs for each syndrome, with most features arising from developmental, functional, or structural anomalies of various organs. The diagnosis can be confirmed with the help of molecular genetic detection, fluorescence in situ hybridization (FISH), or other genetic/chromosomal studies. Treatment is usually symptomatic.

Fragile X: “X-tra large” ears, testes, and face in these patients.

Overview

Prader misses his Papa, and Angel her Mama”: allele mutation/deletion of paternal origin in Prader-Willi syndrome and maternal in Angelman syndrome.

Prader-Willi syndrome [5][6][7]

Angelman syndrome [7][8][9]

Angels in the HEAVENS”: Happy-go-lucky, Easily Excitable personality, Ataxia, Verbal underdevelopment, Epileptic seizures, abNormal facial features, Severe intellectual disability.

  • Definition: X-linked disorder with progressive loss of intelligence and cognitive abilities such as language, locomotion, and fine motor skills [16]
  • Etiology: X-linked dominant gene mutation in methyl-CpG binding protein 2 gene (MECP2 gene)
    • Usually not an inherited gene defect, but rather a sporadic mutation
    • Mutation usually occurs in the paternal allele; thus, females are almost exclusively affected
    • If affected, male fetuses die in utero or shortly after birth.
  • Clinical features
    • Normal development until the first symptoms appear, which typically happens at 6–18 months of age
    • Symptoms of neurodevelopmental regression, including:
  • Diagnosis: : a combination of typical clinical presentation and gene mutation detection
  • Prognosis: There is not enough data regarding life expectancy beyond the age of 40, as long-term studies are not available and the disease is fairly rare.

Rett Regresses: Normal development is shortly followed by a loss of targeted hand movements and intellectual and verbal disability.

William takes ICEcream from strangers (Intellectual disabilities, Cardiovascular malformations, Elfin-like facial features, comfort with strangers).

  • Definition: inherited syndrome with characteristic facial dysmorphia
  • Etiology: CREBBP gene mutation
  • Clinical features
  • Prognosis
    • Usually poor
    • Infants born with this disorder usually survive only to early childhood

References:[17]

Overview of pulmonary alveolar proteinosis [22][23]
Characteristics Primary PAP Secondary PAP Congenital PAP
Autoimmune PAP Hereditary PAP
Definition
  • Syndromes characterized by the progressive accumulation of surfactant protein in the alveoli
Epidemiology [23]
  • > 90% of all PAP cases
  • Prevalence: 6–7:1,000,000
  • Peak age of onset: 30–40 years
  • ∼ 3% of all cases of PAP
  • 5–10% of all cases of PAP
  • ∼ 2% of all cases of PAP
Etiology
  • Genetic mutations
  • Genetic mutations
Pathophysiology
Clinical features
Diagnostics
Treatment
  • Whole lung lavage: excess surfactant is removed from the lungs via saline solution; may require repeated application
  • Subcutaneous injection or experimental inhalation of GM-CSF may be beneficial in autoimmune PAP, as might treatment with rituximab and/or plasmapheresis
  • Treatment of the underlying condition
Complications

References:[24]

  1. Rubinstein-Taybi Syndrome. https://ghr.nlm.nih.gov/condition/rubinstein-taybi-syndrome. Updated: May 2, 2017. Accessed: May 7, 2017.
  2. Treacher Collins Syndrome. https://www.ncbi.nlm.nih.gov/pubmed/20301704. Updated: January 1, 1993. Accessed: July 2, 2020.
  3. Fragile X Syndrome. https://medlineplus.gov/ency/article/001668.htm. Updated: January 8, 2015. Accessed: May 7, 2017.
  4. Fragile X Syndrome. https://ghr.nlm.nih.gov/condition/fragile-x-syndrome. Updated: December 12, 2017. Accessed: December 16, 2017.
  5. Familial Lipoprotein Lipase Deficiency. https://rarediseases.org/rare-diseases/familial-lipoprotein-lipase-deficiency/. . Accessed: September 20, 2021.
  6. Scott LJ. Alipogene Tiparvovec: A Review of Its Use in Adults with Familial Lipoprotein Lipase Deficiency. Drugs. 2015; 75 (2): p.175-182. doi: 10.1007/s40265-014-0339-9 . | Open in Read by QxMD
  7. Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum. https://www.ncbi.nlm.nih.gov/books/NBK1448/. Updated: May 10, 2012. Accessed: May 7, 2017.
  8. Karimi R, Brumfield T, Brumfield F, Safaiyan F, Stein S. Zellweger syndrome: A genetic disorder that alters lipid biosynthesis and metabolism. The Internet Journal of Pharmacology. 2006; 5 (1).
  9. Rett Syndrome Information Page. https://www.ninds.nih.gov/Disorders/All-Disorders/Rett-Syndrome-Information-Page. . Accessed: May 7, 2017.
  10. Mainardi PC. Cri du Chat syndrome. Orphanet J Rare Dis. 2006; 1 (33). doi: 10.1186/1750-1172-1-33 . | Open in Read by QxMD
  11. Schiffer RB, Rao SM, Fogel BS. Neuropsychiatry: A Comprehensive Textbook. LWW ; 2003
  12. Porter FD. Smith–Lemli–Opitz syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2008; 16 (5): p.535-541. doi: 10.1038/ejhg.2008.10 . | Open in Read by QxMD
  13. Smith-Lemli-Opitz Syndrome.
  14. Pulmonary Alveolar Proteinosis. https://rarediseases.org/rare-diseases/pulmonary-alveolar-proteinosis/. . Accessed: September 20, 2021.
  15. McCarthy C, Avetisyan R, Carey BC, Chalk C, Trapnell BC. Prevalence and healthcare burden of pulmonary alveolar proteinosis. Orphanet J Rare Dis. 2018; 13 (1). doi: 10.1186/s13023-018-0846-y . | Open in Read by QxMD
  16. Prader-Willi Syndrome. https://rarediseases.org/rare-diseases/prader-willi-syndrome/. Updated: January 1, 2018. Accessed: June 22, 2020.
  17. Mascari MJ, Gottlieb W, Rogan PK, et al. The Frequency of Uniparental Disomy in Prader-Willi Syndrome. N Engl J Med. 1992; 326 (24): p.1599-1607. doi: 10.1056/nejm199206113262404 . | Open in Read by QxMD
  18. Prader-Willi Syndrome. https://www.ncbi.nlm.nih.gov/books/NBK1330/. Updated: February 4, 2016. Accessed: May 7, 2017.
  19. Prader-Willi Syndrome. https://medlineplus.gov/ency/article/001605.htm. Updated: April 19, 2016. Accessed: May 7, 2017.
  20. Robb MP. Intro: A Guide to Communication Sciences and Disorders, Second Edition. Plural Publishing ; 2013
  21. Angelman Syndrome. https://www.ncbi.nlm.nih.gov/books/NBK1144/. Updated: May 14, 2015. Accessed: May 7, 2017.
  22. Angelman Syndrome. https://ghr.nlm.nih.gov/condition/angelman-syndrome. Updated: November 28, 2017. Accessed: November 30, 2017.
  23. Isolated Pierre Robin Sequence. https://ghr.nlm.nih.gov/condition/isolated-pierre-robin-sequence. Updated: May 2, 2017. Accessed: May 7, 2017.
  24. Drescher F, Jotzo M, Goelz R, Meyer T, Bacher M, Poets CF. Cognitive and psychosocial development of children with Pierre Robin sequence. Acta Paediatr. 2008; 97 (5): p.653-656. doi: 10.1111/j.1651-2227.2008.00742.x . | Open in Read by QxMD
  25. Bhambhani V, Muenke M. Noonan syndrome. Am Fam Physician. 2014; 89 (1): p.37-43.