XXXY Syndrome

What is XXXY Syndrome?

XXXY Syndrome is an abnormal chromosomal condition affects only male individuals. The name of the syndrome indicates extra sex chromosomes is the main clinical presentation of this disorder.

In a normal individual, 46 chromosomes are present. But extra two sex chromosomes present in XXXY syndrome make the chromosomal count 48. Therefore in some medical literature, the XXXY syndrome is also termed as 48 XXXY syndrome1.

XXXY Syndrome  Unique

Incidence Rate

The XXXY syndrome is not frequently occurring disorder. The rate of incidence calculation showed that the ratio varies from 1: 17,000 to 1:50,000 boys are affected with XXXY chromosome2.

Difference between other Sex Chromosomal disorder from XXXY syndrome

There variant type of extra sex chromosome related disorders and they are 47 XXY syndromes, 48 XXXY syndrome, and 49 XXXXY syndromes. Clinical representation of these disorders is inter-related. The symptoms related to dysmorphic features are mild in 47 XXY syndrome, but those features are severe and widespread in 49 XXXXY syndrome.

The intermediate dysmorphic features of these both syndrome are present in 48 XXXY syndrome and commonest sex Chromosomal disorder in comparison of other two1.

XXXY syndrome Vs Klinefelter syndrome

The physical and behavioral distinctiveness make 48, XXXY syndrome different from Klinefelter syndrome. Klinefelter syndrome is also known as 47, XXY because of only one extra sex chromosome. Children with Klinefelter syndrome having delayed speech ability, reading difficulty and unable to understand spelling and face the social problem.

The children having Klinefelter syndrome have lower IQ level in contrast with normal children at same age group, specifically language difficulty due to delay speech. Decreased testosterone secretion level during puberty, though no sexual complication appears.

In XXXY syndrome two extra chromosomes influence more physical, cognitive and behavioral deformed features than Klinefelter syndrome. Delayed motor skill, speech, and social development are more intense due to somatic deformities and mental retardation in XXXY syndrome2,3.


The following sign and symptoms are associated with 48, XXXY syndrome.

  • Impaired cognitive function
  • Fertility issues
  • Internal genital functioning anomalies
  • Speech problem due to nervous system disorder
  • Dental enamel abnormality
  • Structural deformity in shoulder
  • Breathing problem
  • Attention deficit hyperactivity disorder
  • Autism

All the sign and symptoms are slowly progressive from birth to subsequent life span and that can be better to explain it in different sequential paragraphs4.

Time of birth

Infants with XXXY syndrome are quite normal at the time of birth with some minor unusual facial features, like folded skin across the inner angle of the eyes, broad eyes, incurved fifth figures. The external genital feature of the baby is same, but in some infants may not have descended testicle (only one affected) or testicles (both affected).

In some cases, penis size is also decreased than normal babies. Usually the birth weight, height and head circumference of XXXY syndrome children are less than normal babies.

Feeding habit and growth factor

The babies with XXXY syndrome do not face any problem in feeding and can normally feed. But the risk of reflux or backward movement of feeds and related feeding issues can appear as oral-motor functioning is not properly coordinated.

Slim physical structure with a slight belly and decrease muscle development usually appear in XXXY syndrome affected children. In the affected male, the fat distribution is quite similar to female after adolescences and thus belly and waist fat are more in XXXY syndrome affected male.


Usually, puberty starts at normal age with sufficient testosterone level. the physiological changes during puberty like penis size enhancement, facial and body hair growth, voice alterations all are developed gradually.

But at a certain point, testosterone level become decrease and that causes testicles and penis do not completely enlarge, secondary sexual organ are not fully developed.

Enlarged Breast

Some males with XXXY syndrome have enlarged breast, though it is not harmful, but create social embarrassment. Treatment can resolve the problem.

Bone problem

Low level of testosterone often cause lowering of bone density and that leads to osteoporosis.

Dental problem

The dental abnormality occurs due to enlargement of the inner chamber of the teeth and that is termed as taurodontism. Some XXXY syndrome male does not have permanent teeth or get enamel abnormality and defective incisors shape3.


The exact cause of XXXY syndrome is not fully clear. Some experts believe that the XXXY syndrome is not inherited and erratic cell division causing defective mutation of the chromosomes.

The extra chromosome may come from mother or father, though there is no chance of both parents are involved. Normally X chromosome from female partner and Y chromosome from male partner together formed fertilize an egg for a baby boy.

But in XXXY syndrome, either Y-bearing sperm fertilize XXX chromosome bearing egg or XXY sperm fertilizes X chromosome of the egg. The increased age of female partner may be a concerning point for chromosomal defective childbirth, though the definite cause is not known3,4.


XXXY Syndrome is a non-curable disorder, but certain intervention can reduce complications and helpful to face their problem positively.

  • Intensive speech and communication therapy can improve speaking ability and also improve social life.
  • Occupational therapy can improve their functional ability
  • Social skills training programs are extremely useful as these provide an understanding of social signal and correct responses.
  • Stainless steel crowns are applied for taurodontism treatment. Consultation with dentist is also important to treat other dental related problem
  • Consultation with an endocrinologist is very important for management of genital issues and bone disorder. The doctor may suggest treating with testosterone for solving some problems related to declining of testosterone level and loss of bone density.
  • Physiotherapy can improve somatic deformities and useful for delay mobility.
  • A metabolic disorder like obesity and the related problem can be managed with consulting experts.
  • Neurological disorders also require medical treatment depending upon the symptoms3,4,5.


The survival rate of XXXY Syndrome affected individuals are same as a normal individual. Early diagnosis and different interventions can improve patient quality of life. A Periodic visit to the clinic and proper follow-up is required for life long to monitor the patient condition and maintain their healthy life4,5.


  1. XXXY Syndrome; Encyclopedia of Child Behavior and Development; pp 1584-1585; Online available at
  2. 48, XXXY Syndrome; Online available at
  3. XXXY Syndrome; Understand Chromosome Disorder Unique;; Online available at
  4. 48, XXXY Syndrome; Genetic and Rare Disease Information center; Online available at
  5. 48,XXXY syndrome;; Online available at

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