• Clinical science

Rare inherited syndromes


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. 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 syndrome

Fragile X → X-tra large → big ears, testes, face


Prader-Willi syndrome and Angelman syndrome

Prader misses his Papa: In Prader syndrome, the Paternal allele is mutated/deleted. In AngelMan syndrome, the Maternal allele is mutated/deleted.

Prader-Willi syndrome

Angelman syndrome

  • Clinical features
    • Delayed mental development and acquisition of motor skills in infants and young children
    • In more than 80% of cases, pronounced epileptic seizures
    • Microcephaly
    • Ataxia, tremulous movements of the limbs
    • Truncal hypotonia, limb hypertonia, hyperreflexia
    • Difficulty sleeping
    • Intellectual disability
    • Characteristic happy demeanor with frequent laughing (inappropriate laughter)
    • Hyperexcitability, short attention span
    • Fascination with water
  • Treatment
  • Prognosis: Life expectancy is typically normal.


Zellweger syndrome (cerebrohepatorenal syndrome)


Pierre Robin sequence (Pierre Robin syndrome)


Cri-du-chat syndrome (cat cry syndrome)

  • Definition: rare syndrome caused by a chromosome 5 aberration.
  • Epidemiology: sex distribution: > (2:1)
  • Etiology: microdeletion of the short arm at chromosome 5 (46,XX or XY, 5p‑).
  • Clinical features
    • Cat-like, high-pitched crying in affected infants
    • Cardiac abnormalities (VSD)
    • Intellectual disability (moderate to severe)
    • Single palmar crease
    • Dysmorphic facial features (e.g., microcephaly, epicanthal folds, broad nasal bridge, downward-slanting palpebral fissures, moon facies, widely spaced eyes)
    • Skeletal abnormalities
  • Treatment
    • Symptomatic treatment
    • Early psychological and physical assistance
  • Prognosis: A normal life expectancy is possible, but depends on the accompanying symptoms and therapeutic assistance.


Rett syndrome

  • Definition: X-linked disorder with progressive loss of intelligence and cognitive abilities such as language, locomotion, and fine motor skills
  • Etiology: X-linked dominant gene mutation (in methyl-CpG binding protein 2 [MECP2] gene)
    • Usually not an inherited gene defect, but rather a sporadic mutation. The mutated copy of the MECP2 gene is often associated with the paternal allele, as it occurs randomly during spermatogenesis → primarily females are affected
  • Clinical features
    • Affects females almost exclusively
    • Normal development and then onset between 7–24 months of age
  • Diagnosis: : a combination of typical clinical presentation and gene mutation detection

Rett syndrome Regresses: After normal development, loss of targeted hand movements and intellectual and verbal disability occurs!


Williams syndrome

To remember important clinical features of William-Beuren syndrome, think: William takes ICEcream from strangers (Intellectual disabilities, Cardiovascular malformations, Elfin-like facial features, comfort with strangers).


Smith-Lemli-Opitz syndrome


Albright hereditary osteodystrophy (Martin-Albright syndrome)


Noonan syndrome


Silver-Russell syndrome