49,XXXXX - The Focus Foundation

What is Pentasomy X (Penta X) Syndrome?

Penta X Syndrome is an extremely rare chromosomal disorder that only affects females. While girls normally only have two X chromosomes, girls with Penta X have five X chromosomes. As of 2011, less than 40 cases have been reported.

What causes Penta X?

Chromosomes are the 46 rod-like structures containing your DNA that are organized into 23 pairs per cell. The 23rd pair are your two sex chromosomes: either two X chromosomes for girls (XX) or one X and one Y chromosome for boys (XY).

During a process called meiosis, chromosome pairs separate and the mother’s egg (her reproductive cell) is normally left with a single X chromosome. However, there may be errors made during this process in which the chromosome pairs fail to separate, resulting in a cell with an extra X chromosome (also called non-disjunction). If the error is made again with both of those X chromosomes, the following cell can end up with four X chromosomes. The fifth X comes from an X-carrying sperm that fertilizes the egg. When this happens, the egg will develop into a baby with five X chromosomes, or Penta X syndrome.

What causes Penta X?

Girls with Penta X Syndrome typically have delayed growth, resulting in short stature and trouble gaining weight. During infancy and childhood, girls with Penta X may exhibit motor delays, moderate to severe intellectual disability, and speech and communication difficulties. Some girls may experience delayed puberty as well.

What can I do to help my child with Penta X?

Early intervention is key in providing the best outcome for girls with Penta X. Parents may find genetic counseling, special education, physical therapy, speech therapy, and other symptom-related services to be beneficial for not only the child, but also their families and/or caretakers.


The most common features of girls with Penta X include:

Short stature

Malformations of the skull and craniofacial region

Wide-spaced eyes with upslanting eyelid folds (palpebral fissures)

A flat nasal bridge

Low-set, malformed ears

A short neck with a low hairline

Small head size (microcephaly)

Thin enamel, abnormally shaped molars, and an opening on the roof of the mouth (cleft palate)

Curved inward (clinodactyly) and permanent flexion (camptodactyly) of the “pinkies” or fifth fingers

Hyperextension of the elbows and fusion of the forearm bones (radioulnar synostosis)

Unusually close knees and increased space between the ankles (genua valga)

Overlapping toes and club foot (metatarsus varus)

Heart and/or kidney defects

Deficient development of the ovaries and uterus

Related X & Y Disorder Research

X&Y Variation Disorders encompass individuals who are born with 45, 47, 48, or 49 chromosomes, rather than the standard 46. The Focus Foundation’s efforts are centered on disorders resulting from having 47, 48, and 49 chromosomes. 45, X (also known as Turner’s Syndrome) occurs in one out of 2,000 live female births and is actively and effectively served by The Turner Syndrome Society. Below are more details about X&Y Variations involving 47, 48, and 49 chromosomes:

Only 25% of males with 47,XXY are ever diagnosed during their lifetimes; fewer than 10% of 47,XXY individuals are identified prior to adolescence. This means that millions of affected children remain undiagnosed–often because they are commonly misdiagnosed as simply having speech or motor delays. More than 500,000 people are believed to have 47,XXY disorders in the United States alone, with an equal distribution across all racial and socio-economic groups.

Based on scientific studies, it is important to consider early hormonal replacement therapy (EHRT) for 47,XXY boys (who experience decreased testosterone production during three critical developmental periods) before they are 18 months old. Testosterone treatment given then has been shown to have a positive impact on brain function through 9 years of age…READ MORE

At least 85% of those with 47,XYY are never diagnosed. 47,XYY boys consistently present with language-based Learning Disabilities and difficulties with Motor Planning–both issues that are related to the high rate of dyspraxia and dyslexia associated with the disorder. However, 47,XYY boys are commonly misdiagnosed as simply having speech or motor delays.

Boys with 47,XYY typically reach an average height of between 6’3” and 6’5”…READ MORE

As many as 1 in 900 girls have 47,XXX. Unfortunately, millions of affected girls are undiagnosed. Girls who are prenatally diagnosed and receive early intervention services typically exhibit fewer and less severe cognitive disabilities.

There is an equal distribution of 47,XXX across all racial and socio-economic groups…READ MORE

48,XXXX (also known as Tetrasomy X or Tetra X) is a rare sex chromosome disorder that was first identified in the early 1960s. Since that time, approximately 100 cases have been reported, although less than 50 are described in scientific literature. Due to the scarcity of this female chromosomal variation, it is difficult to define a common phenotypic presentation. A lack of congenital malformations, mild dysmorphology, and varied developmental trajectory suggests that 48,XXXX is largely underdiagnosed…READ MORE

48,XXXY can result from meiotic or mitotic nondisjunction (errors in chromosomal separation) and is often considered a variant of Klinefelter syndrome (47,XXY). However, boys with 48,XXXY often exhibit a more complicated neurodevelopmental profile than boys with 47,XXY…READ MORE

The first case of 49,XXXXY syndrome was reported in the 1970s, and this chromosomal variation remains one of the rarest sex chromosome disorders. 49,XXXXY results from nondisjunction (errors in chromosomal separation) of the X chromosome occurring during both Meiosis I and Meiosis II…READ MORE

Penta X Syndrome is an extremely rare chromosomal disorder that only affects females. While girls normally only have two X chromosomes, girls with Penta X have five X chromosomes. As of 2011, less than 40 cases have been reported.…READ MORE

Klinefelter Syndrome & Other Names You May hear

X & Y Variations is a neurogenetic disorder known by many names, among them: Sex Chromosome Disorders, X & Y Chromosomal Variations, Sex Chromosome Anomaly and Sex Chromosome Aneuploidy Variations. Within the disorder are many sub-categories, which are identified by names including 47 XXY (Klinefelter Syndrome), 49 XXXXY, Tetrasomy X, 49 XXXXXX, Pentasomy X, 48 XXY.

What You Can Do Now

If you have received a prenatal diagnosis indicating that your child has an X & Y chromosomal variation, or feel that your son or daughter is experiencing developmental delays or developmental dysfunction, the following options are designed to help you take the next step in securing appropriate treatment or an early diagnosis.


Take The Child Questionnaire



Learn About Chromosomal Microarray

Chromosomal Testing


Begin Syndrome-specific Therapy