What medical care may a child with CdLS need?

What medical care may a child with CdLS need?


Paediatric Medical Care

CdLS is usually recognised from birth by an experienced children’s doctor (paediatrician or clinical geneticist). Paediatricians or clinical geneticists play a key part in the clinical care of a child with CdLS. Once an infant or child has been diagnosed with CdLS, they will need to be assessed for common structural abnormalities of the body associated with the syndrome. These may require management or surveillance.

Individuals with CdLS may have heart and/or kidney malformations (birth defects) (49). Every infant and young child diagnosed with CdLS should have a heart and kidney assessment by an echocardiogram (heart scan) and kidney ultrasound respectively. If malformations are found, the child may need to be referred to a specialist to help with management. If the diagnosis is made in adolescence, these tests may not be necessary if related symptoms have not been reported (R10).

Rarely, some children with CdLS may show neurological symptoms such as seizures. Seizures are caused by an abnormal discharge of electrical activity in the brain. A test of electrical activity in the brain (electroencephalogram, or EEG) can assess for seizures. Routine brain imaging (e.g. CT or MRI scans) is usually not recommended unless indicated to be of clinical use.

Treatment and surveillance of malformations in children with CdLS are the same as for typically developing children. However, the procedure of intubation (inserting a tube through the mouth into the airway during medical procedures) has been difficult in many children with CdLS. Children may also have an adverse allergic reaction to some anaesthetic medications (such as Midazolam or Versed), though complications from most anaesthetic medications are rare (52,53).

Growth in Childhood

Birth weights in CdLS are significantly lower than the average birth weight and children with CdLS are almost always short in stature. Young children tend to have a below average weight when compared to others their age, although obesity can occur in later life. A small head size is also often common in individuals with CdLS. Growth charts are available that are specific to individuals with CdLS (54). CdLS-specific growth charts should be used to monitor the growth of every child with CdLS (R11).

Growth in CdLS is influenced by the specific gene implicated in the development of CdLS (10,24). Individuals with CdLS caused by a change in SMC1A tend to show more growth than individuals with CdLS caused by a change in NIPBL (3). If growth is lower than expected in CdLS, there may also be gastrointestinal (stomach/intestines) problems, thyroid gland dysfunction (leading to dysfunction in bodily functions such as metabolism, growth and development) or growth hormone disturbances.
The release of growth hormone (important for growth, body structure and metabolism) is normal in most children with CdLS (55). However, a case study with one child with CdLS (NIPBL mutation) with low growth hormone levels experienced a growth increase after being administered growth hormone injections (56). The benefits of increased growth from growth hormone supplementation should be weighed against the burden of daily injections and the lack of positive impact of an increased adult height on quality of life for most individuals with CdLS.

Feeding and Dental Difficulties

From infancy to adulthood, feeding difficulties are very common in individuals with CdLS. Preferably, individuals with CdLS should be fed orally (by mouth). However, feeding difficulties may sometimes result in feeding times becoming unsafe, stressful and taking many hours out of the day. In these circumstances, doctors may temporarily supplement an individual’s feeding with a gastrostomy tube (57). A gastrostomy tube delivers food straight into an individual’s stomach. It is important that dieticians (experts on diet and nutrition) are involved (R12, R13).

Feeding difficulties can be caused by several physical issues such as a cleft palate, micrognathia (undersized jaw) or dental issues (57). Cleft palate is where there is a gap or split in the roof of the mouth. It is present from birth and occurs in 20% of individuals with CdLS. After being diagnosed with CdLS, all individuals should have the roof of their mouth closely examined to assess for cleft palate. If an individual has a cleft palate, they should be referred for specialist assessment (R14).

Dental problems in CdLS may include:

  • Delayed secondary tooth eruption
  • Small or absent teeth
  • Malposition (abnormal positioning of teeth)
  • Malocclusion (misalignment between the lower and upper teeth when the jaw closes)
  • Overcrowding of teeth
  • Tooth decay or cavities
  • Periodontal disease (infection affecting the gums of the mouth)
  • Bruxism (teeth grinding)

Dental problems may worsen due to poor oral hygiene, especially in individuals with CdLS who have marked intellectual disability. Sometimes, individuals with CdLS may not brush their teeth regularly or thoroughly enough. This may lead to early onset dental decay and periodontal (gum or mouth) disease(59). It is important to ensure regular dental assessment and cleaning to prevent early dental decay. A healthy diet can also help to keep teeth in good condition (61,60 ; R15).

Motor Development

Motor development refers to the development of a child’s bones and muscles the child’s ability to move around and manipulate the environment. Motor development can be divided into gross motor development (involving the larger muscles) and fine motor development (involving the small muscles of the body).

Motor development in CdLS is almost always delayed and developmental milestones should be monitored closely (R16). There is some evidence to suggest children with CdLS caused by a SMC1A gene mutation may reach milestones (e.g. sitting, walking and first words) at a younger age than children with CdLS caused by changes in the NIPBL gene (3). By five years of age, most children with CdLS caused by a change in NIPBL are able to sit, walk independently and start to speak.

Vaccinations should be given to every child with CdLS according to national guidelines (R17). It is common for individuals with CdLS to have recurrent respiratory infections which can affect the sinuses, throat, airways or lungs. Respiratory infections in CdLS are thought to be influenced by differences in anatomy (how the airways have formed), hypotonia (low muscle tone and strength) and poorer co-ordination of swallowing and coughing.
Some individuals with CdLS may have an immunodeficiency. This is where the body’s immune system has a lower ability to fight infection. If the child with CdLS has unusually frequent or severe infections, the GP or paediatrician can make a referral to assess for an immunodeficiency (62).

Thrombocytopenia (low platelet count) can also occur in CdLS. Platelets are blood cells which help the blood to clot to stop bleeding (e.g. when a person falls and grazes their knee). Specific testing is not needed for thrombocytopenia in CdLS and individuals tend to not show symptoms (63,63).

Pain and Behaviour

Pain in CdLS can be caused by dental problems, bladder and upper respiratory tract (including ears and sinuses) infections, gastro-oesophageal reflux disease (GORD) and/or hip abnormalities. GORD is a condition in which a weakness in the muscles above the stomach allows stomach acid to move upwards into the oesophagus. Due to limited communicative abilities, individuals with CdLS may be unable to report pain and it may be difficult to identify the cause (65). Pain in CdLS can lead to substantial behavioural difficulties.

Scales have been developed to help identify pain in individuals who have difficulties communicating. If it is suspected that a person with CdLS is in pain, the Face, Legs, Activity, Cry, Consolability (FLACC) scale is a useful tool that can assist in identifying pain (66). The FLACC scale can help to identify different sources and symptoms of pain in a person with CdLS (R18).

Puberty

Most individuals with CdLS will go through puberty, though puberty is usually mildly delayed. The average age of puberty onset in CdLS is 15 years of age in boys and 13 years of age in girls (2). A small number of females with CdLS will never menstruate. For those who do menstruate, the menstrual cycle will often be irregular. Most girls with CdLS will develop breast tissue.

Some females with CdLS may have a bicornuate (heart-shaped) womb. There are no extra difficulties with conception or in early pregnancy for women with a bicornuate womb, however, there is a slightly higher risk of miscarriage and premature birth.

Boys with CdLS may have undescended testicles, a small penis and/or hypospadias (where the opening through which urine passes is not at the tip of the penis) (2). Only a small number of boys with CdLS have hypospadias. Undescended testicles are very common in males with CdLS. There are risks associated with not having corrective surgery, including a heightened risk of developing testicular cancer, hernias, and twisting of the testicle. Usually there is no lowering of voice at puberty for boys with CdLS (2).

Teenagers with CdLS can become overweight or develop obesity. This is often related to the consumption of high calorie food in combination with limited physical activity (2). Regular evaluation of weight is important.

Paediatric Follow-Up

Preferably, all individuals with CdLS should be followed up by a paediatrician or clinical geneticist experienced in CdLS. Follow-up varies between countries but is frequent in infancy and early childhood, and make occur annually to once every 3–5 years in adolescence and adulthood. In case of problems, the schedule should be adapted to include more frequent follow-up visits (R19).

Medical Care in Adulthood

Most people with CdLS reach adulthood because of improved care, especially in the first year of life. Several individuals with CdLS have lived to 50+ years of age (23,67). Many medical disciplines tend to be involved in the medical care of adults with CdLS. As many disciplines are involved, it is important that there is co-ordination in care.

Can individuals with CdLS have children?

A small number of women with CdLS have given birth. Often, mothers have only been diagnosed after their child has been diagnosed with CdLS (3,36,41,68). Few men with CdLS have fathered a child, though there is little data about fertility in males with CdLS (69,70 70). Sexual education should be offered to individuals with CdLS and education should be appropriate to the level of understanding. Contraceptive options are the same as for the general population (R20).

For some women with CdLS it may be preferable to control or prevent menstruation. There are several contraceptives that can do this. Hysterectomies are not recommended as a primary method of contraception in CdLS. A hysterectomy is a surgical procedure to remove the womb and means the woman can no longer become pregnant. However, a woman with CdLS may have a hysterectomy to treat unusually heavy periods which do not respond to treatment (R21).

Premenstrual syndrome (physical and emotional symptoms occurring before a period) and menstrual period pain occur in women with CdLS and can be associated with behavioural changes. Treatment options are the same as in the general population. It is not known if women with CdLS undergo menopause.

Weight Management in Adulthood

Some adults with CdLS are overweight and may be obese (49,59). Close attention should be paid to ensuring a healthy, low calorie diet and physical activity is encouraged (R22).

A very small number of adults with CdLS develop type 2 diabetes (2). Type 2 diabetes is a common condition that causes high sugar (glucose) levels in the blood, resulting in excessive thirst and tiredness. Individuals who are overweight have a higher risk of developing type 2 diabetes.

How are the Organs Affected in Adults with CdLS?

Organ involvement in adults with CdLS is similar to that seen in children with CdLS. Heart defects are common in CdLS and around 1 in 4 children with CdLS are born with a heart condition. These are usually detected in infancy or childhood. Typically, heart defects do not cause unexpected complications in adulthood. A small number of individuals with CdLS may have hypertension (high blood pressure) or heart failure (where the heart is unable to pump blood around the body properly) (2,73). A very small number of individuals with CdLS have been reported to have a heart attack or stroke (73).

It has been identified that a number of individuals with CdLS have structural differences in their kidneys. Even so, kidney failure has only been reported in 1% of individuals with CdLS (73). The kidneys are responsible for filtering waste products from the blood, alongside regulating blood pressure, electrolyte balance and red blood cell production. When there are structural differences in the kidneys, they may not be able to function properly. Kidney function should be monitored regularly in children and adults with CdLS who have structural kidney malformations (R23).

Prostate enlargement has been found in 10% of men with CdLS by the age of 41 years. The prostate is a small gland located between the penis and the bladder. Enlargement of the prostate can cause difficulty with urination. Prostate enlargement is common in men aged over 50 in the general population (75). Prostate enlargement in men with CdLS should be assessed earlier and treated according to national guidelines for the general population (R24).

Risk of Cancer in CdLS

There is no increased risk of cancer at a young age in CdLS in comparison to the general population. It is unclear whether there is an increased risk of cancer for middle-aged and older individuals with CdLS. Cancer of the oesophagus has been reported in three individuals with CdLS who had Barrett’s oesophagus. This can be caused by Gastro-oesophageal reflux disease (GORD) which is common in CdLS. GORD is a condition in which a weakness in the muscles above the stomach allows stomach acid to travel into the oesophagus. Over many years, stomach acid can cause changes in cells lining the oesophagus. This is called Barrett’s oesophagus. These abnormal cells are at increased risk of becoming cancerous.

Women with CdLS should be offered cervical and breast cancer screening according to national guidelines for the general population (77,78) (R25, R26).

Causes of Death in CdLS

The most common causes of death in infants with CdLS are congenital diaphragmatic hernia (hole in the diaphragm) and respiratory (breathing) problems. In children with CdLS, the most common causes of death are heart defects and respiratory and gastrointestinal (stomach/intestines) problems (73).

Causes of death in adults with CdLS relate to gastrointestinal, pulmonary (lung) and cardiac (heart) systems, as well as infections or anaesthesia (medically induced loss of sensation) (2,67,73,79).

Several countries use emergency medical cards which report the main clinical data of the patient. The use of these emergency cards should be considered for every person with CdLS (R27). Emergency cards can report the most frequent and potentially life-threatening medical complications of CdLS.

summary section

Paediatric Medical Care:

R10: Every infant and young child with CdLS should be assessed for cardiac (heart) and renal (kidney) malformations subsequent to diagnosis.


R11: The growth of every child with CdLS should be monitored by using CdLS-specific growth charts.


R12: In every CdLS individual with prolonged and marked feeding difficulties, the multidisciplinary assessment (from healthcare workers across many disciplines) should consider (temporary) placement of a gastrostomy (surgical opening through the abdomen into the stomach) as a supplement to oral feeding.


R13: In individuals with CdLS who have recurrent respiratory infections, reflux and/or aspiration (breathing foreign objects into airways) should be ruled out.


R14: The palate should be closely examined at diagnosis. In case of symptoms of a (submucous) cleft palate, referral for specialist assessment is indicated.


R15: Dental assessment and cleaning should take place regularly; a more thorough dental examination or treatment under anaesthesia may be necessary.


R16: Developmental milestones should be closely monitored.


R17: Vaccinations should be given to every child with CdLS according to national guidelines.


R18: As pain can easily remain unrecognised in a child with CdLS, all care providers should be aware of the different manifestations and the possible sources of pain. Specific tools to assess pain are recommended.


R19: Regular follow-up of every child with CdLS is needed, preferably by a paediatrician or clinical geneticist experienced in treating individuals with CdLS; schedules depend on local practices and possibilities.

summary section

Medical Care in Adulthood:

R20: Sexual education appropriate to the level of understanding should be offered, and contraception management should follow local standard for the general population.


R21: Hysterectomy is indicated if abnormally heavy bleeding at menstruation is present and does not respond to medical treatment.


R22: Specific attention to diet and stimulation of activities are recommended as obesity can occur.


R23: Renal (kidney) function should be regularly monitored in children and adults with CdLS who have structural renal malformations.


R24: Prostate enlargement in men with CdLS should be treated according to national guidelines for the general population.


R25: Women with CdLS should be offered breast cancer screening according to national guidelines for the general population.


R26: Routine gynaecologic care including cervical screening should be performed in women with CdLS, according to national guidelines for the general population.


R27: The use of emergency cards should be considered for every person with CdLS.

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