What Does the General Pediatrician Do When There Are Concerns for a Rare Disease?

Patient Presentation

An 8-year-old male came to clinic for his health supervision visit. He was doing well overall including school where he got special help for some reading problems. His mother also complained that he still had nocturnal enuresis about once per week. It was not bothering him but she didn’t like doing all the extra laundry. The family history was positive for his father who had nocturnal enuresis until about 10 years old. His mother had just recently found out she was a carrier for Bardet-Biedl syndrome. She said she didn’t have any personal problems including normal eyesight but that she knew there were renal problems associated with it and wondered if he needed to see a urologist because of the enuresis and possible Bardet-Biedl syndrome. The review of systems was negative.

The pertinent physical exam showed a happy male with growth parameters at 95% for weight and 50% for height. He had normal vital signs including blood pressure and vision screening of 20/20 bilaterally. His physical examination was normal including his eye, genital, and neurological examination.

The diagnosis of a healthy male with probably primary nocturnal enuresis was made. The laboratory evaluation showed a normal urinalysis. The pediatrician also made a referral to a urologist because of the mother’s concern about Bardet-Biedl syndrome after discussing with her that this was an autosomal recessive disorder and was unlikely. However the child did also have some learning problems and was at 95% for weight both of which could be signs of the syndrome. The urologist ordered a renal ultrasound which was normal and started the child on a bedwetting alarm.

Bardet-Biedl syndrome (BBS) is a rare disorder. It is usually considered an autosomal recessive disorder but there is significant intra-familial variability. There are multiple genes (~20 currently) involved and it is believed that the phenotypic variability is due to “…differences in the total mutational load across different BBS associated genes….” It is a ciliopathy where mutation changes in proteins in the cilias causes problems in the cilia’s functioning particularly signaling. Cilia are important in signaling to maintain tissue and cellular homeostasis. Obviously screening of affected family members would be important, particularly siblings as they would have ~25% chance of being affected. Genetic counseling for future pregnancies is also important.

BBS is usually diagnosed with a patient having 4 primary features or 3 primary and 2 secondary features. Polydactyly will be present at birth but the other problems usually develop over the first 2 decades.

  • Primary features
    • Rod-cone dystrophy -> 90% affected, usually before adulthood and is usually the reason for most morbidity
    • Obesity (central) – 72-92% affected, less severe in childhood but increases with age
    • Polydactly – 63-81% affected
    • Learning problems/Mental retardation – 50-61% affected with various learning problems, speech, intellectual disabilities and behavior problems
    • Hypogonadism – 59-98% affected, males generally have micropenis and/or small testes and often are infertile, females have various forms of hypoplasia
    • Renal abnormalities – 20-53% affected, renal concentrating defects without other functional or structural abnormalities are the most common problem, dysplasia and glomerular disease also occur
  • Secondary
    • Atopy
    • Diabetes – 6-48% affected
    • Hepatic fibrosis

    • Brachyactyly/syndactyly
    • Dental abnormalities
    • Facial dysmorphism
    • Anosmia/hyposmia

    • Behavior problems
    • Neuro-motor problems – 46-86% affected
    • Speech deficits – 54-81% affected
    • Hearing loss – 11-12% affected

    • Cardiac problems
    • Hypertension – 30-60% affected
    • Respiratory problems

    • Hypothyroidism

Differential diagnosis includes several syndromes that have obesity as a presentation including:

  • Alstrom syndrome
  • Biemond syndrome type II
  • Joubert syndrome
  • Laurence-Moon syndrome
  • McKusick-Kauyman syndrome
  • Meckel syndrome
  • Prader-Willi syndrome
  • Senior-Loken syndrome

A review of primary nocturnal enuresis can be found here.

A review of diurnal enuresis can be found here.

A review of common causes of blindness in children can be found here.

Learning Point
The patient and family will almost always know more about the specific uncommon disease than the pediatrician. However, general pediatricians’ know about human bodies, physiology and treatment principles. They know how to monitor patients, how to evaluate other family members, interpretate medical vocabulary and the medical literature, and how to help families understand legitimate differences of opinion as to evaluation, management and treatment. General pediatricians may need help from medical specialists to work with the family to meet all of these needs. General pediatricians can also be helpful in supporting the family with a new diagnosis or ongoing chronic disease. This could include referrals to community services, school services and mental health services. The general pediatrician often treats the other siblings and parents often have many concerns about the potential problems for other family members. Being available for families to ask questions, and navigate multiple systems are important aspects of what a general pediatrician can do for families. The general pediatrician can also be a sounding board regarding “how far” to go with the evaluation or trying a new treatment regime as they often have an ongoing relationship and understand the families’ values regarding health care and what may be functional to do in their own home.

Questions for Further Discussion
1. How would the potential management change for an autosomal dominant or variable penetrance genetic disorder?
2. What is the pediatrician’s role in genetic testing?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Retinal Disorders, Kidney Diseases and Birth Defects.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Novas R, Cardenas-Rodriguez M, Irigoín F, Badano JL. Bardet-Biedl syndrome: Is it only cilia dysfunction? FEBS Lett. 2015 Nov 14;589(22):3479-91.

Khan SA, Muhammad N, Khan MA, Kamal A, Rehman ZU, Khan S. Genetics of human Bardet-Biedl syndrome, an updates. Clin Genet. 2016 Jul;90(1):3-15.

Agrawal H, Dokania G, Allen HD. Visual Diagnosis: Visual Impairment, Polydactyly, and Obesity: Red Flags in a Child. Pediatr Rev. 2018 May;39(5):e21-e23.