SDS Info

Clinical Characteristics of Shwachman-Diamond Syndrome

This article is a publication of the Communications Committee of Shwachman-Diamond Canada. It has been edited for medical accuracy by members of the Medical Advisory Board. This article may be copied and distributed provided it is distributed in its entirety. Individual sections should not be abstracted and distributed out-of-context.


Primary features of Shwachman-Diamond Syndrome

  • Hematologic abnormalities
  • Pancreatic defect
  • Skeletal abnormalities
  • Small stature at all ages, poor growth in childhood

Other, less consistent, features of Shwachman-Diamond Syndrome

  • Dental
  • Liver
  • Eating habits
  • Kidney
  • Eye Problems
  • Skin
  • Problems in Infancy
  • Early Development
  • Heart problems

The Genetics of Shwachman-Diamond Syndrome

The Diagnosis of Shwachman-Diamond Syndrome

Further Reading

  • Summary articles
  • Large case series
  • Copyright Information

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Shwachman-Diamond Syndrome (SDS) is a rare genetic disorder. It affects many organs in the body but the effects are variable; different people have different symptoms. On the basis of current knowledge, all people with SDS appear to have a pancreatic defect and hematologic abnormalities. Many have skeletal abnormalities and short stature. There are a very wide variety of additional complications that can affect some individuals with SDS.

It is not known exactly how frequently SDS occurs. Medical researchers estimate that it affects approximately 1 in 50,000 births, but there is no scientific basis for this number because we lack a simple way of establishing the diagnosis. Some physicians think it may be more common than this because certain people with Shwachman syndrome may be mis-diagnosed as having something else. Conversely, some people who have been diagnosed as having SDS may not have it.

This document presents the various clinical characteristics of Shwachman-Diamond Syndrome sorted into two categories: the primary features (those that are likely a direct result of the genetic fault that causes Shwachman-Diamond Syndrome) and the secondary features (those that are less consistently observed; some may be caused by complications arising from the primary features).

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Primary features of Shwachman-Diamond Syndrome

The following features (hematologic abnormalities, pancreatic defect, skeletal abnormalities and small stature) are considered primary features of SDS because they appear to arise directly as a result of the genetic fault. They are also the most commonly observed features.

Hematologic abnormalities:

In the bone marrow, blood cells are produced from very young cells called stem cells. Three types of blood cells are produced: 1) white blood cells, including neutrophils, which fight infection; 2) red blood cells, which carry oxygen to all parts of the body; and 3) platelets, which help the blood to clot. All people with SDS have at least one hematologic abnormality as a result of their bone marrow functioning poorly.

Most people with SDS (98%) have neutropenia (low neutrophil count). In about 2/3 of these, the neutropenia is intermittent (it can come and go and neutrophil counts may be normal between episodes of neutropenia) and in the remaining 1/3, the neutropenia is constant (it is present all the time). People with SDS also have another neutrophil problem. Their neutrophils may not have the ability to find and destroy bacteria properly. This is called “poor neutrophil mobility” and “impaired chemotaxis.

As a result of these neutrophil problems, people with SDS are at risk of getting infections easily and often. Sometimes these infections can be serious, even life threatening, because of the reduced ability to fight infection. Infections can occur in many places including the lungs, ears, sinuses, mouth, throat, blood, bones or skin. Prompt recognition of infection and early treatment is essential.

People with SDS can have other hematological abnormalities as well: 42% have anemia (low red cell count), 34% have thrombocytopenia (low platelet count) and 19% have pancytopenia (all cell counts low). Serious bone marrow complications can develop. One possible complication is bone marrow failure which results in significant under-production of all blood cells (aplastic anemia).

Some SDS patients develop acute myelogenous leukemia (AML). The risk is likely around 20-25%, although individual studies have reported either lower or higher rates. AML is a particularly serious form of leukemia with a low survival rate. It is believed by many hematologists that treatment is more likely to be successful if the leukemia is detected early. For this reason, some doctors recommend regular bone marrow analysis in the hope of detecting early pre-leukemic changes in the bone marrow before full-blown leukemia occurs.

The leading causes of death in people with SDS are infection, leukemia and bone marrow failure.

Pancreatic Defect

The pancreas has two functions: 1) the production of digestive enzymes (the “exocrine” function of the pancreas); and 2) the production of insulin which regulates blood sugar (the “endocrine” portion of the pancreas).

People with SDS have a defective exocrine pancreas. However, the endocrine portion of the pancreas is likely to remain normal for most people with SDS.

The pancreatic “acinar” cells are the cells which produce digestive enzymes. The “normal” pancreas has excess capacity; only 2% of the acinar cells need to be functional in order to produce adequate quantities of enzymes to digest the food one eats. If a person has less than 2% of their exocrine pancreatic capacity, then the patient produces insufficient amounts of digestive enzymes and cannot digest food properly. The medical term for this is pancreatic insufficiency.

Since they have inadequate numbers of functioning acinar cells, people with SDS usually have pancreatic insufficiency in early childhood. However, with increasing age, up to 50% of SDS patients have some improvement in enzyme production and can become pancreatic sufficient. However, the underlying pancreatic defect is still present.

The symptoms of pancreatic insufficiency are bulky, foul smelling or loose stools. These symptoms indicate that the intestines are not absorbing all of the fat and nutrients from food (malabsorption). This can lead to malnutrition and vitamin deficiencies (particularly vitamins A, D, E and K) and other nutritional deficiencies.

Pancreatic insufficiency can be treated by taking replacement enzymes with meals. As well, vitamin supplementation is usually advised. In later childhood, those who show a slight improvement in enzyme production may be able to decrease or even discontinue their replacement enzymes.

Skeletal Abnormalities

Approximately one-half of children with SDS have a skeletal abnormality called “metaphyseal dysostosis” or “metaphyseal dyschondroplasia”. When present, it usually occurs in the hips but can also occur in the knees. This is an abnormality that is visible by x-ray but it does not necessarily cause any symptoms or clinical problems. However, sometimes the part of the bone that grows (the growth plate or “metaphysis”) can be affected. Rarely, the top of the femur (the bone that runs from the hip to the knee) will develop too small an angle to the hip (coxa vara) or the knee joint can be affected causing “knock” knees or “bowed” knees. If present, these problems may require surgery.

Approximately one-half of children with SDS have x-ray changes of the cartilage in the vicinity of the ribcage (costochondral thickening).This does not cause symptoms or clinical problems.

Approximately one-third of children with SDS have rib cage abnormalities including shortened ribs with flared ends and a narrow rib cage. These may, uncommonly, lead to breathing difficulties in the newborn period (severe versions of this are called thoracic dystrophy). This usually resolves as the child gets older.

Other skeletal problems have been reported rarely. These include clinodactyly (bent fingers), osteopenia (thinning of the bone), growth arrest lines, vertebral collapse, slipped femoral epiphysis (dislocation of the end of the femur) and duplicated distal thumb phalanx (an extra thumb).

Small stature at all ages, poor growth in childhood:

Some children with SDS are smaller than average at birth. By age 1 and later, most children with SDS are shorter than average when compared to children of the same age and sex. Over half are below the 3rd percentile for height.

Most children with SDS are not underweight or malnourished after diagnosis and treatment with enzymes. Their weights are appropriate for their heights.

Even after being treated with enzymes and achieving normal nutritional status, most children with SDS will continue to be small. Small stature (being shorter than average) is a primary feature of Shwachman Syndrome and correction of nutritional status and enzyme therapy will not alter this.

One consequence of small size is delayed puberty. Although it is socially difficult for a teenager to reach puberty later than their friends, it is actually good news in terms of their physical growth because this means that the teenager will continue to grow for a longer period of time. Once puberty occurs, there is a growth spurt, but there is also only a limited amount of time that the skeleton can continue to grow.

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Other, less consistent, features of Shwachman-Diamond Syndrome

The features described below are only observed in some people with SDS. Like many genetic syndromes, SDS manifests differently in different people and variation in symptoms from person-to-person is quite substantial; some people have many of these while others have few or none of these secondary features.


Children with Shwachman Syndrome may have poorly developed teeth. The medical term for this is “dental dysplasia”. The cause is unknown but perhaps it is one of the skeletal defects of the disease.

As well, there is increased risk of tooth decay (possibly due to neutropenia), tooth enamel defects (possibly a skeletal defect or possibly caused by plaque leaching calcium from the teeth), delayed teething (possibly due to slow growth) and periodontal disease (possibly due to neutropenia).

As with other conditions involving neutropenia, people with SDS can lose their teeth due to periodontal disease. People with neutropenia should see a dentist at least every 6 months and have their teeth professionally scaled and fluoridized regularly. The periodontal literature also suggests that, during an episode of neutropenia, daily use of an anti-microbial mouthwash called “Peridex” may be helpful.

Discuss with your doctor whether or not antibiotics are needed for routine dental work and surgical procedures.


Liver problems are often observed in people with SDS. These problems are very mild in nature and usually of little consequence.

Liver enzyme (serum transaminase) abnormalities have been observed in approximately 60% of people with SDS. Approximately 15% of people with SDS have been observed to have an enlarged liver (hepatomegaly). Those with hepatomegaly are not necessarily the same people who have liver enzyme abnormalities.

These abnormalities are more common in younger rather than older children and may disappear with age for many patients.

Eating habits

Some children with SDS have larger than normal appetites. This is a symptom of their malabsorption; they are not absorbing all their food and so they eat more to fill their calorie requirements.

Other children are reported to eat very small amounts and are described as picky eaters. To some degree, appetite is determined by growth. A child who is not growing as quickly will eat less food because the body is not demanding food for growth. If weight-for-height is appropriate, then the child is likely consuming adequate amounts of food.

Very rarely, significant feeding difficulties arise requiring tube feeding.


There have been occasional reports of kidney stones in people with SDS. The cause of these may be increased concentrations of a compound called oxalate (which is a salt in certain foods). This is likely caused by malabsorption; the fat in the intestines causes too much oxalate to be absorbed from food in the intestines.

Very rare kidney conditions include renal tubular acidosis (incorrect kidney pH causing biochemical imbalance). One SDS patient was reported to have renal lithiasis (calcium deposits in the kidney) and another patient had an extra ureter (the tube connecting the kidney to the bladder).

Eye Problems

Ptosis (drooping of upper eyelid) has been reported in a few people with SDS. Strabismus (misdirected eye), coloboma (congenital defect of eye tissue) and punctate keratitis (inflamation of the cornea, perhaps due to vitamin A defficiency) have each been observed once in different individuals with SDS. It is not known if these are part of SDS. When present, these conditions are observable very soon after birth.


In early childhood, some children with SDS have skin problems. This can occur on the scalp (cradle cap) or elsewhere. The symptoms may be skin rashes or dry, rough or scaly skin (ichthyosis). This is usually outgrown in early childhood. The cause is unknown; but it may be due to nutritional deficiencies (likely fatty acid deficiency but perhaps vitamin deficiency) caused by malabsorption.

Problems in Infancy

Occasional neonatal problems include breathing and feeding problems. Either of these may be a result of shortened ribs or may be a result of infection.

Often, in infancy, the infant either does not gain weight or even loses weight (failure to thrive). The cause is poor digestion. Therapy which improves the child’s digestion and nutrition intake will cause the child to begin to gain weight at an acceptable rate. However, growth failure is a primary feature of SDS and correction of nutritional status will not alter this.

Early Development

People with SDS have the same range of intelligence as the general population; most have normal IQ, a few are intellectually challenged and a few are intellectually gifted.

Motor delays and/or speech delays have been reported as an occasional problem for children with SDS in early childhood. Some children with developmental delays will show catch up of the delay by school age. However, for others, developmental delays may be an early indicator of later learning difficulties. One medical survey of 88 people with SDS reported that 16% had learning disorders and 3% had attention deficit disorder.

Some SDS parents comment that their children are behaviorally challenging. Because this has not been researched, we do not know the percentage of children who experience this or the cause. There are many factors that can influence development including early childhood infections (such as middle ear infections), nutritional compromise in early childhood and, perhaps, the social effects of having a chronic condition which requires lots of attention and medical support.

Heart problems

There have been a few reports of individuals with enlarged heart (right-sided hypertrophy) as a result of chronic lung disease. As well, a medical article from Finland reported some SDS children with myocardial fibrosis. There are no reported cases of myocardial fibrosis in children with SDS from any other countries. However, myocardial fibrosis is a known, but uncommon, complication in cystic fibrosis.

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The genetics of Shwachman-Diamond Syndrome

Every characteristic of an individual is determined by at least one pair of genes. Each pair of genes is inherited; one from the father and one from the mother. An inherited disease is caused by a faulty gene. SDS is autosomal recessive; in order to have the disease, the genetic fault must occur in both genes. The father and mother each may have one good gene and one faulty gene. They do not have the disease but are carriers of the faulty gene. However, the person with SDS inherited the faulty gene from each parent and therefore has the disease because he/she has two defective genes.

In each pregnancy, parents of children with SDS have a 25% chance of giving birth to a child with SDS (a child who has inherited a faulty gene from both parents). There is a 50% chance that a child will inherit one defective gene and one good gene and be a healthy “carrier” of the defective gene (just as the parents are). There is a 25% chance of a child inheriting two good genes and therefore not carry the faulty gene at all. In each pregnancy, the chance of having another child with SDS is the same; the risk does not change based on how many children the parents have.

Someone with SDS likely will not have children with SDS unless their spouse is also a carrier of this rare genetic fault.

The genetic fault has recently been identified in the laboratory of Dr. Johanna Rommens and Dr. Peter Durie (link to Hospital for Sick Children press release). The actual mechanism whereby each organ is affected is not yet known.

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Diagnosis of Shwachman-Diamond Syndrome

The variation in clinical features makes this a very difficult disease to diagnose.

The diagnosis is generally based on evidence of exocrine pancreatic and hematologic abnormalities. Skeletal abnormalities and short stature are characteristics that can be used to support the diagnosis.

Now that the gene has been identified, it is expected that clinical laboratories will introduce genetic tests in the near future.

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Further Reading

The clinical features of SDS vary substantially from person-to-person and you should not assume that all of the information in this document applies to you or a member of your family. Your own physician can help you determine which aspects of the condition do apply.

Medical publications on any subject can be mis-leading. This is partially because diagnostic standards may vary from place to place and over time. As well, due to the variable nature of this illness, individuals may have very different clinical features than the people discussed in medical publications.

The following recent articles contain complete, up-to-date information about SDS. Some information will change as more becomes known.

Summary articles

Gaskin KI. Hereditary Disorders of the Pancreas. Chapter 29 part 3 in Walker, Dune, Hamilton, Walker, Watkins (ed). Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis, Management, Vol 2; published by BC Decker, Philadelphia 1989.

Lopez MJ, Grand RJ. Hereditary and Childhood Disorders of the Pancreas. Chapter 79 in Sleisenger MH, Fordtran JS, Gastrointestinal Diseases: Pathophysiology/Diagnosis and Management. Published by Sunders, Philadelphia, 1993.

Schreiber RA. Congenital Diseases of the Exocrine Pancreas. Chapter 67 in Wyllie & Hyams (ed) Pediatric Gastrointestinal Disease: Pathophysiology, Diagnosis and Management. Published by Saunders, 1993.

Silverman A and Roy CC. Exocrine Pancreatic Insufficiency. Chapter 27 in Silverman & Roy, Pediatric Clinical Gastroenterology, 3rd edition. Published by Mosby, 1993.

Large case series

Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR. Shwachman Syndrome: Phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar. Journal of Pediatrics 135:81-88, 1999.

Mack DR, Forstner GG, Wilschanski M, Freedman MH, Durie PR. Shwachman Syndrome: Exocrine Pancreatic Function and Variable Phenotypic Expression. Gastroenterology 111: 1593-1602, 1996.

Smith OP, Hann IM, Chessells JM, Reeves BR, Milla P. Haematological abnormalities in Shwachman-Diamond Syndrome. British Journal of Haematology 94: 279-284, 1996.


Boocock, GRB, Morrison, J, Popovic, M, Richards, N, Ellis, L, Durie, PR, Rommens, JM. Mutations in SBDS are associated with Shwachman–Diamond syndrome. Nature Genetics, 2002.

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