About bulldog syndrome

What is bulldog syndrome?

Simpson dysmorphia syndrome types 1 and 2 are two forms of a rare, X-linked recessive, inherited disorder characterized by unusually large fetuses (prenatal overgrowth) and unusually large babies (postnatal overgrowth). In addition, affected individuals have characteristic facial features, more than two nipples (super-numerary nipples), and multisystemic malformations that may vary from child to child. Chief among these are cardiac malformations, mild to moderate mental retardation, cleft palate, and more than the five fingers and/or toes (polydactyly).

Symptoms associated with the more common form, Simpson dysmorphia syndrome type 1 (SDYS1), are less severe than those presented in SDYS2.

Individuals usually reach an above-average height. The general distinguishing features typically become less apparent in adulthood.

What are the symptoms for bulldog syndrome?

Simpson-Golabi-Behmel Syndrome Type 1

Many different parts of the body can be affected when a person has SGBS. Not every person with SGBS has the same symptoms, and none have all of these symptoms.


  • General Muscle Weakness and low muscle tone (hypotonia) in 61% of people
  • Large size (macrosomia)


  • Abnormal shape of the skull due to early bone fusion (craniosynostosis)
  • Large jaw (macrognathia) in more than half of affected people
  • Large sized head (macrocephaly) in the majority of affected people
  • Specific facial feature that don’t look like other family members
    • Large forehead
    • Large and thick nose and lips
    • Large tongue with a groove in the middle going from the front to the back in the majority of people
    • Opening in the roof of the mouth (cleft palate) in 1 out of 4 people
    • Split opening in the lip (cleft lip) in 1 out of 4 people

Central Nervous System

  • Attention deficit hyperactivity disorder
  • Build-up of fluid in the brain (hydrocephalus)
  • Disorder that causes breathing to pause or slow down during sleep (obstructive sleep apnea)
  • Intellectual disability in about half of people
  • Seizure disorder (epilepsy)

Speech and Language

  • Speech disorder in the majority of people


  • Any type of abnormality of the heart in about 1 out of 3 of people


  • A weak area or defect in the belly that allows organs to push through (abdominal wall defect) in 1 out of 3 people
  • Abnormal opening in the muscle between the chest and abdomen that helps with breathing and is present at birth (congenital diaphragmatic hernia) occurs rarely
  • Extra nipples (supernumerary nipples) in half of people
  • Kidney abnormalities in 33% of people
    • Large kidney (nephromegaly) in half of people
    • Large liver (hepatomegaly) in half of people
    • Large spleen (splenomegaly)
  • Organs that are larger than they should be (organomegaly) in most people


  • Opening of where the urine comes out (urethra) on the underside of the penis instead of at the tip (hypospadias)
  • Testes that do not descend properly and are still inside the body (cryptorchidism)


  • Abnormalities of the hands and feet
    • Broad thumbs
    • Extra fingers or toes (polydactyly)
    • Large hands
    • Short fingers and toes (brachydactyly) in half of people
    • Underdevelopment of the pointer finger (index finger hypoplasia)
    • Webbed or conjoined 2nd and 3rd fingers (syndactyly of the 2nd-3rd fingers)
  • Chest deformity in less than half of people
  • Rib malformations
  • Scoliosis in one out of ten people


  • A 10% risk for certain tumors including:
    • Adrenal neuroblastoma (a cancer found in the adrenal glands on top of the kidneys)
    • Gonadoblastoma (a tumor with cells from the early testes or ovaries)
    • Hepatoblastoma (cancerous liver tumor)
    • Hepatocellular carcinoma (most common form of liver cancer)
    • Medulloblastoma (a brain cancer that starts in the brain at the base of the skull)
    • Wilms tumor (a kidney cancer seen in children)


  • Birth before 37 weeks (prematurity) in half of people
  • Low blood sugar as a newborn (neonatal hypoglycemia) in 1 in 4 people
  • More amniotic fluid than there should be (polyhydramnios) in the majority of people

Simpson-Golabi-Behmel Syndrome Type 2

SGBS type 2 is more serious and rarer than type 1. Boys with SGBS type 2 usually die a few months after birth. Most affected boys are born with extra fluid in multiple parts of the body (hydrops fetalis) and they also can have problems with their bones, distinct facial features, issues with organs and other medical problems.

What are the causes for bulldog syndrome?

SGBS type 1 is caused by harmful changes (mutations) in the genes GPC3 and GPC4, located on the X chromosome. SGBS type 2 is caused by mutations in the genes OFD1 and PIGA, also located on the X chromosome. They are genetic disorders that are inherited in a recessive X-linked pattern.

The gene glypican 3 (GPC3) contributes to the control of growth and changes in this gene may lead to overgrowth. It is thought that organs of the body such as the heart and liver reach normal size when the GPC3 protein is available in large enough quantities. Concentration is sufficient when GPC3, the growth inhibiting factor, balances the growth promoting factors, such as insulin-like growth factor 2, IGF2.

SGBS is inherited in an X-linked pattern. X-linked genetic disorders are conditions caused by a mutation in a gene on the X chromosome. Mutations are changes in the way that genes, the body’s instructions, are written that cause the genes to not work in the way they should. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. Some female carriers of SGBS have symptoms, but if they do their symptoms are normally mild. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.

What are the treatments for bulldog syndrome?

The treatment for SGBS is based on the type of symptoms that each individual patient has. In the newborn period, right after birth, the baby’s blood sugar levels should be monitored to make sure they are not too low (hypoglycemia). The baby should also be checked to see if they are having problems breathing (airway obstruction). If the baby has any problems with their kidneys (renal anomalies) then their kidney function should also be monitored. Physical examinations should be done to check for a sideways curvature of the spine (scoliosis) during periods of time when the child is growing quickly. Social and intellectual development should also be monitored routinely.

Individuals with cleft palate require the coordinated efforts of a team of specialists. Pediatricians, dental specialists, surgeons, speech therapist, and psychologists must systematically and comprehensively plan treatment and rehabilitation. The palate may be repaired surgically or covered by an artificial device that closes or blocks the opening. Speech and language development need to be assisted by a speech therapist during the preschool years.

For a complete list of different specialists to see based on the specific concern, reference the GeneReviews (listed under Internet sources) for Simpson-Golabi-Behmel Syndrome Type I.

Genetic counseling is recommended for patients and their families

What are the risk factors for bulldog syndrome?

SGBS is present from birth (congenital) and can be diagnosed in a baby, even though some of the features might not appear until a child is older. All males who have a mutation in one of the genes for SGBS will have the condition. It is not known what percentage of carrier females have symptoms. As of 2014, there were 250 known cases of SGBS type 1. As of 2019, there have been 8 symptomatic female carriers reported.

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