49,XXXXX syndrome

Alternate names

Pentasomy X; Chromosome XXXXX syndrome; Penta-X syndrome; Pentasomy X syndrome; Chromosome X pentasomy

Definition

Pentasomy X is a sex chromosome anomaly caused by the presence of three extra X chromosomes in females (49,XXXXX instead of 46,XX).

File:Foetal karyotype demonstrating pentasomy X.png

Epidemiology

The prevalence is unknown but less than 40 cases have been described in the literature so far.

Cause

• Pentasomy X is generally thought to arise as a result of successive maternal nondisjunction during meiosis.
• The features of the syndrome likely arise due to failure of X-inactivation and the presence of multiple X chromosomes from the same parent causing problems with parental imprinting.
• In theory, X-inactivation should occur and leave only one X chromosome active in each cell. However, failure of this process has been observed in one individual studied.
• The reason for this is thought to be the presence of an unusually large, and imbalanced, number of X chromosomes interfering with the process.

Signs and symptoms

• Pentasomy X is associated with developmental delays, short stature, craniofacial anomalies and musculoskeletal abnormalities. T
• he craniofacial anomalies may include microcephaly, micrognathia, plagiocephaly, hypertelorism, upslanting palpebral fissures, a flat nasal bridge and ear malformations.
• The hands and feet are generally small and camptodactyly, clinodactyly, and radioulnar synostosis are common findings.
• Immunoglobulin anomalies and an increased susceptibility to infection have also been reported. Cardiovascular malformations may also be present.
• External genitalia are generally normal but gonadal dysfunction has been reported.
• Developmental profiles usually show global developmental delay and intellectual disability; however, receptive language skills are usually less severely affected than expressive language abilities.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Low-set, posteriorly rotated ears
• Muscular hypotonia(Low or weak muscle tone)

30%-79% of people have these symptoms

• Camptodactyly of finger(Permanent flexion of the finger)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Global developmental delay
• Hypertelorism(Wide-set eyes)
• Intellectual disability(Mental deficiency)
• Microcephaly(Abnormally small skull)
• Micrognathia(Little lower jaw)
• Plagiocephaly(Flat head syndrome)
• Radioulnar synostosis(Fused forearm bones)
• Short foot(Short feet)
• Short stature(Decreased body height)
• Small hand(Disproportionately small hands)
• Strabismus(Cross-eyed)
• Upslanted palpebral fissure(Upward slanting of the opening between the eyelids)
• Wide nasal bridge(Broad nasal bridge)

5%-29% of people have these symptoms

• Abnormal cardiac septum morphology
• Abnormality of immune system physiology
• Delayed puberty(Delayed pubertal development)
• Hip dysplasia
• Patent ductus arteriosus

Diagnosis

Diagnosis is suspected based on symptoms and confirmed by chromosomal analysis.

Treatment

Treatment is based on symptoms.

NIH genetic and rare disease info

• NIH info on 49,XXXXX syndrome

49,XXXXX syndrome is a rare disease.