XXXXY is an extremely rare sex chromosomal abnormality occurring in approximately 1 out of 85,000 to 100,000 males.
Due to lack of information and awareness that surrounds a diagnosis of XXXXY it is misunderstood and often mismanaged. It is no surprise, given the vast range of serious medical conditions affecting human beings, that many medical professionals are perhaps only vaguely familiar with X and Y chromosome variations, a health professional and health care provider’s learning are never done.
Prenatal testing is significantly increasing due to its availability and continued advancements and therefore the incidence of prenatal diagnosis of XXXXY is also increasing. Many expectant parents are completely unaware that these tests can also identify X & Y sex chromosome variations. These tests can be obtained via analysis of the mother’s blood known as the Harmony test or NIPT. Many babies or infants with XXXXY if not diagnosed prenatally are diagnosed shortly after birth as a result of a chromosome tests run due to their small genitals. Other signs such as an unusual shaped head, unusually formed ears and broad forehead may also indicate a chromosomal disorder. Although a substantial proportion are diagnosed during their first year after development due to difficulty in taking longer to reach their developmental milestones.
A diagnosis of XXXXY in babies and children assessment and testing is made based upon a thorough clinical evaluation, a detailed patient history, and specialised blood tests for chromosomal analysis that detect the presence of three extra X chromosome (49,XXXXY karyotype). The most common type of testing is a specialised blood test known as karyotyping. Children and adults displaying a combination of speech and language delays, motor delays, difficulty particularly with reading, displaying impulsive and challenging behaviour with attention difficulties and have a tall stature should have a blood karyotyping carried out to confirm or rule out an XXXXY diagnoses.
Health care providers play an integral role in a child and individuals’ life who has XXXXY, they are vital to ensure that rates of early diagnoses significantly increase and are also key to ensure that the several health risks of XXXXY are minimised and managed.
It is important to remember that individuals with an XXXXY diagnosis will be affected in different ways.
Prenatal Diagnoses
What health care professionals should be involved in a prenatal diagnosis of XXXY?
- Health professionals that should be involved are:
- Obstetrician
- GP
- Midwife (depending on the model of care expectant parents choose)
- Maternity hospital
What are common signs and symptoms and health implications for a prenatal diagnosis of XXXY?
Babies with XXXY usually look much like any other baby at birth although some may have slightly unusual facial features, such as skin folds across the inner corners of the eye (epicanthic folds) or wide set eyes (hypertelorism). Some have unusual hand features such as a single palm crease or incurving fifth fingers. In some babies the penis is very small (micro phallus). Babies with XXXY may be smaller than average newborns in height and weight.
Children
What health care professionals should be involved in a child’s life who has XXXY?
Essential health care provider team:
- GP: For regular check-ups, health checks, referrals to appropriate specialists and services and for the development of chronic disease management plans and mental health care plans if required.
- Paediatrician
- Paediatric Endocrinologist
- Maternal and child health Nurse
- Dentist
Likely health care provider and early intervention services team:
- Speech therapist
- Occupation therapist
- Physiotherapist
- Psychologist or Psychiatrist
- Podiatrist
- Early educator support
What are common signs and symptoms for a child with a diagnosis of XXXY?
The appearance of signs and symptoms of XXXY in childhood can vary greatly and range from mild to those that have a significant impact on a child. It is important for health care providers to remember that XXXY is a spectrum condition – its effects vary enormously in both incidence and severity. Many of the signs and symptoms of XXXY also occur in children with other conditions, or children who do not have an underlying diagnosis, which makes detecting XXXY in childhood more difficult. Some of the common and potential signs and symptoms in a child with XXXY are:
- Low muscle tone (hypotonia)
- Reduced muscle strength or tone can sometimes lead to other complications such as sleep apnoea or chronic constipation
- Speech delay/expressive language disorder: language difficulties is extremely widespread, most commonly verbal dyspraxia.
- Mild autism
- Developmental delays e.g. Grabbing objects, crawling, walking, talking etc.
- Learning difficulties: IN particular reading disorders
- Attention deficits/ADHD
- Depression/anxiety: Very high incidence
- Sensory processing challenges: Are very common and may include aversion to loud noises or over stimuli in busy environments
- Micro phallus
- Undescended testes
- Hypogonadism (low levels of testosterone)
- Clinodactyly: Curved pinky finger
- Poor motor development or coordination (dyspraxia)
- Tiredness and fatigue
- Difficulties processing information – especially verbal
- Shy and timid nature
- Poor communication and social skills
- Display challenging behaviour
- Long, thin arms and leg
- Overall IQ may be below their age-matched typical peers
- Abnormal fusion of certain bones in the forearm (radioulnar synostosis)
- An unusually large range of joint movement (hyperextensibility)
- Elbow abnormalities
- Flat feet (pes planus)
- Distinctive facial features (may or may not be evident): including widely spaced eyes (ocular hypertelorism), outside corners of the eyes that point upward (up slanting palpebral fissures), and skin folds covering the inner corner of the eyes (epicanthal folds).
Adolescents and adults
What health care professionals should be involved in an adolescent and adult who has XXXY?
Essential health care provider team:
- GP: For regular check-ups, health check, referrals to appropriate specialists and services and for the development of chronic disease management plans and mental health care plans if required.
- Paediatrician up until 18 years old
- Paediatric Endocrinologist and then Endocrinologist
- Dentist
- Likely health care providers team:
- Speech therapist
- Occupation therapist
- Physiotherapist
- Psychologist or Psychiatrist
- Podiatrist
- Educational support in school and throughout further education
- Individual tutor
- Vocational support
What are common signs and symptoms for an adolescent and adult with a diagnosis of XXXY?
XXXY is often apparent at puberty, when the expected physical changes don’t occur. It is important for health professionals to remember that the appearance of signs and symptoms of XXXY in adolescents and adults can vary greatly and range from mild to those that are more significant, its effects vary enormously in both incidence and severity. Individuals are often misdiagnosed with other conditions prior to receiving a diagnosis of XXXY. Some of the common and potential signs and symptoms in an adolescent and adult with XXXY include:
- Small testicles (hypogonadism) – males with XXXY always have small firm testicles from puberty
- Lack of facial, pubic and underarm hair
- Poor muscle development
- Breast tissue development (gynaecomastia)
- Unexplained weight gain, especially on the stomach or trunk
- Tiredness and fatigue
- Micro phallus
- Undescended testes
- Disproportionately long arms and legs compared to the length of the body
- Taller than average height
- Poor short-term memory
- Poor concentration, ADHD is very common
- Clinodactyly: Curved pinky finger
- Single crease in the palm (simian crease)
- Speech and learning difficulties, most commonly verbal dyspraxia – in some cases this can lead to behavioural problems
- Learning difficulties usually associated with spelling, reading and writing
- Lack of co-ordination (dyspraxia)
- Difficulty expressing themselves
- Difficulties processing information – especially verbal
- Poor social development
- Autistic tendencies
- Display challenging behaviours
- Sadness, lowered mood or depression and anxiety
- Dislikes sports, particularly team sports
- Poor communication and social skills
What are common health implications for a child and individual with a diagnosis of XXXY?
It is essential that health care providers understand the health implications associated with XXXY and recognise that compared with males in the general population, XXXY is associated with an increased risk of certain diseases and conditions. Appropriate follow up, assessments and tests are required to ensure these health implications are identified and treated early. The following health implications may be evident in a child or individual with XXXY:
- Diabetes type 1 and
- Osteoporosis
- Diabetes mellitus
- Lung disease: Chronic bronchitis, asthma
- Breast cancer
- Testicular cancer
- Prostate cancer
- Anaemia
- Infertility
- Mental health concerns: Depression, anxiety or other psychiatric conditions
- Leukaemia
- Non-Hodgkin lymphoma
- Thyroid disease
- Autoimmune diseases: rheumatoid arthritis, psoriasis and inflammatory bowel syndrome (IBS).
- Sleep apnoea
- High cholesterol
- Dental problems: Tooth decay, taurodontism, thin teeth enamel
- Venous conditions: Varicose veins, leg ulcers, deep vein thrombosis (blood clots in veins) and pulmonary embolism (blood clots in the lung)
- Essential tremor and unbalanced gait
Health care providers can have a huge positive impact on a person’s life who has XXXY. An earlier diagnosis provides opportunities for the child and his family to access treatments and interventions that can help overcome any difficulties associated with the condition. A collaborative approach is essential to decrease the stress and burden and health implications for those with XXXY.
Together we can all make an immense positive change to increasing early diagnoses and decreasing the health impacts that XXXY has on a child and individual.
