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48,XXYY syndrome

Synonym(s) -
Prevalence Unknown
Inheritance Not applicable
or Unknown
Age of onset Infancy
  • Q98.8
  • C2936741
  • D007713
  • 10048230


Disease definition

The 48,XXYY syndrome represents a chromosomal anomaly of the aneuploidic type characterized by the presence of an extra X and Y chromosome in males.


There is an annual incidence of 1/18,000 to 1/50,000 male births.

Clinical description

The 48,XXYY syndrome can be considered as a variant of Klinefelter syndrome (see term) as it shares the same clinical phenotype (tall stature, infertility, microorchidism, hypergonadotropic hypogonadism) but in addition includes behavioral problems (anxiety, aggressiveness, communication difficulties), psychiatric problems (hyperactivity, depression, etc.) and general minor language and learning troubles (reading difficulty, dyslexia). There is also sometimes minor intellectual deficit (average IQ of 77). A delay in motor development, often associated with hypotonia, is frequently observed. Very minor, non-specific facial dysmorphism (hypertelorism, epicanthal folds, facial assymetry, flat occiput) and other dysmorphic characteristics (clinodactyly, pes planus, prominent elbows with cubitus varus, etc.) are more frequently observed than in Klinefelter syndrome. Congenital heart defects and skeletal anomalies (radioulnar synostosis) can also be present. Neurological (epilepsy), dental (thin enamel, delay in eruption of teeth, taurodontism), ophthalmological (strabismus) and digestive (gastro-esophageal reflux) problems are frequent during childhood. With age, other symptoms can appear, such as tremor, scoliosis, obesity, type 2 diabetes and/or respiratory problems (asthma, respiratory infections).


The most probable etiology is the non disjunction of homologous chromosomes (during the first meiotic division) or sister chromatids (during the second meiotic division) during spermatogenesis. There is no known factor responsible or predisposing to this syndrome.

Diagnostic methods

The metaphase karyotype allows for the confirmation of a clinical diagnosis.

Differential diagnosis

Differential diagnoses include the other aneuploidies, such as Klinefelter (47,XXY) syndrome, 48,XXXY syndrome and 49,XXXXY syndrome (see these terms).

Antenatal diagnosis

Antenatal diagnosis is possible by performing amniocentesis.

Genetic counseling

The risk of recurrence is very low, with cases of 48,XXYY being sporadic.

Management and treatment

Management needs to be performed by a multidisciplinary team and includes the correction of heart defects and skeletal anomalies, as well as the management of sensory (ophthalmological examination), neurological, hormonal (testosterone-based hormone therapy), metabolic (thyroid and diabetes monitoring), respiratory, psychological and psychiatric care and of digestive problems. Regular dental follow-up is also recommended.


Patients have an essentially normal life expectancy but will need to attend regular medical visits, in particular for their respiratory and endocrine problems and their predisposition to infections. Patients should also be followed-up by a psychiatrist (in childhood and adulthood).

Expert reviewer(s)

  • Dr Carole CORSINI
  • Pr Pierre SARDA

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