Simpson-Golabi-Behmel syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at August 26, 2016
StartDiseasesSimpson-Golabi-Behmel syndrome

Simpson–Golabi–Behmel syndrome (SGBS) was named for two American geneticists, Joe Simpson and Mahin Golabi, and an Austrian geneticist, Annemarie Behmel. The disorder has been known by several names, including Golabi-Rosen syndrome, Gigantism-dysplasia syndrome, and Simpson dysmorphia syndrome.

Contents

Definition & Facts

There are currently only 130 diagnosed cases of Simpson-Golabi-Behmel syndrome worldwide, with approximately 250 cases reported to date. Cardiovascular disease is the suspected cause of the 50 percent mortality rate in infancy of males who have the disease, but those with milder forms can live in to adulthood.

It is a rare congenital disorder which affects mostly male patients; however some female genetic carriers show evidence of the condition. Classified as an overgrowth syndrome, it is often diagnosed at birth, presenting itself with larger than normal infants who display unusual physical traits and debilitating disabilities.

In the year 2000, a clinic for Simpson-Golabi-Behmel syndrome was established by Dr. Michael R. Debaun and Dr. Scott Saunders at the St. Louis Children's Hospital. Dr. Debaun, a pediatrician specializing in oncology and epidemiology, created a registry for patients diagnosed with SGBS.

The registry allows the physicians to further their research by giving them the resources to keep in touch with the families and their pediatricians as the children age and new complications become evident. Currently, the registry contains only 17 families. With the results of their research, the team has developed a test confirming the gpc3 mutation, believed to be present in 30-40 percent of SGBS patients.

Symptoms & Complaints

The physical characteristics of patients with Simpson-Golabi-Behmel syndrome include a unique facial appearance with a large protruding jaw, enlarged tongue, and a wide nose.

Other facial deformities may include cleft lip and clef palate, improperly aligned teeth, and widely spaced eyes.

SGBS can cause abnormal development of the extremities. Patients may present with broad hands and feet with shortened and wide toes and fingers.

SGBS causes unique symptoms involving the chest and abdomen as well, including infants born with extra nipples, defects in the muscle tissue of the abdomen, and hernias. Other symptoms include:

  • Neonatal hypoglycemia. This occurs when an infant's blood sugar level is below 40mg.
  • Developmental disabilities. Patients with SGBS may present with a varying degree of intellectual disabilities, but this symptom does not occur in every case. Some patients with SGBS grow to adulthood with normal cognitive abilities.
  • Advanced bone age. Bone age tells us how quickly a child's skeletal system is maturing. An advanced bone age in relation to the age of the child may be an indicator of SGBS.
  • Talipes. Also known as club foot, this is a congenital deformity, giving the appearance that the ankle has been rotated inward and affects either one foot or both. Children with this deformity appear to be walking on their ankles. Corrective surgery may be required to improve patient mobility.
  • Hypotonia. Commonly referred to as “floppy baby syndrome,” hypotonia is a marked lack of muscle tone, giving the infant an almost rag doll-type of appearance. Infants may have difficulty feeding, show signs of shallow breathing and be prone to dislocation of hip, dislocation of jaw, and neck dislocations. Hypotonia can be an indicator of SGBS as well as other congenital diseases. Its cause can be either neurological or non-neurological.
  • Seizures. These episodes of rhythmic spasms appear differently in infants than what we're accustomed to seeing in adults. Infant seizures are shorter and more subtle, making them more difficult to identify. Parents should pay close attention to sudden stiffening of arms and legs, sudden, irregular movement of the upper body and a measurable change in responsiveness.
  • Tumors. An increased risk for abdominal tumors is an indicator of SGBS. Wilms' tumor, a tumor of the kidney, hepatoblastoma - a tumor found in the liver, and gonadoblastoma, a tumor-like growth that is usually benign (non-cancerous) are types typically found in patients with Simpson-Golabi-Behmel syndrome.

Causes

Simpson-Golabi-Behmel syndrome is caused by a genetic mutation inherited from the parents. It is considered an X-linked genetic disorder because the mutations occur on the X-chromosome which is one of two sex chromosomes.

Diagnosis & Tests

SGBS can be diagnosed prenatally if the family knows that the genetic mutation causing the syndrome has already been identified among other family members. Testing for the syndrome can begin as early as 16 weeks of gestation. This is accomplished through a prenatal ultrasound, making the detection of abnormal fetal growth possible.

Testing may also indicate the accumulation of fluid in the scalp, lungs or abdomen. Detection of abnormal enlargement of the abdominal organs can also become evident during the ultrasound. The mother may be checked for elevated serum alpha-fetoprotein levels, another indicator of SGBS.

If the disease is suspected at birth, diagnosis is made from clinical results obtained from genetic testing for specific mutations, family history, ultrasounds, and X-rays to identify skeletal abnormalities as well as the testing of renal function.

Treatment & Therapy

Treatments for SGBS will vary widely, dependent upon the specific complications for each case. These may include surgeries to correct physical deformities and to repair internal organs or speech therapy to overcome difficulty caused by an enlarged tongue. Patients with developmental difficulties can benefit from special education and occupational therapy.

Physical therapy may be implemented to improve mobility when limbs and musculoskeletal system are affected. Cardiac function should be monitored regularly by a cardiologist, due to the prominence of congenital heart defects in patients with Simpson-Golabi-Behmel syndrome. During the first five years of life, patients should be regularly screened for the development of kidney tumors, because of the increased risk. Recommended testing to detect tumors includes abdominal ultrasound and urinalysis.

Prevention & Prophylaxis

Due to Simpson-Golabi-Behmel syndrome being caused by a genetic defect, the only course of prevention is the testing of both the male and female parent prior to conception. If the male has the mutation or the female is a carrier, there is an increased chance that the child will be born with SGBS.