Translate this page into:
A syndromic puzzle: Diagnosing Bardet–Biedl syndrome in adulthood
, Shilpa Terrence1, Nazia Bhati1
-
Received: ,
Accepted: ,
How to cite this article: Surabhi N, Rajadhyaksha G, Sharma A, Sadigale V, Terrance S, Bhati N. A syndromic puzzle: Diagnosing Bardet– Biedl syndrome in adulthood. Med India. 2026;5:53-6. doi: 10.25259/MEDINDIA_44_2025
Abstract
An Indian male in his mid-20s presented with breathlessness, pedal edema, and abdominal distension. Clinical examination revealed dysmorphic features, including a broad nasal bridge, a short neck, an upward slanting palpebral fissure, micrognathia with an underdeveloped chin, a flat fascial profile, and low set ear, along with minimal secondary sexual characteristics. Electrocardiogram showed incomplete right bundle branch block and P pulmonale, while echocardiography revealed severe pulmonary hypertension, myxomatous mitral valve with prolapse of the anterior leaflet, and severe tricuspid regurgitation. Further evaluation identified right renal agenesis and hypergonadotropic hypogonadism. Ophthalmological examination was normal. The constellation of features led to a clinical diagnosis of Bardet-Biedl Syndrome. This case emphasizes the importance of clinical suspicion and multidisciplinary evaluation in diagnosing syndromic disorders.
Keywords
Hypogonadism
Pulmonary hypertension
Myxomatous mitral valve
Renal agenesis
Syndromic diagnosis
INTRODUCTION
This case represents a rare instance of adult-onset clinical diagnosis of Bardet–Biedl syndrome (BBS) in a resource-limited setting, where genetic testing was unavailable. BBS is a rare autosomal recessive ciliopathy characterized by multisystem involvement, including retinal dystrophy, polydactyly, obesity, hypogonadism, renal anomalies, and cognitive impairment.[1,2]Diagnosis is typically based on a combination of primary and secondary features. Although BBS is typically identified in childhood, delayed diagnosis into adulthood can occur due to its heterogeneous phenotype and variable expressivity. The absence of classical findings such as retinal dystrophy further complicates recognition. This case adds to the scientific literature by highlighting the diagnostic value of clinical criteria in settings where next-generation sequencing is inaccessible and underscores the importance of considering BBS in adults presenting with unexplained cardiopulmonary abnormalities alongside syndromic physical features.
BBS with significant cardiopulmonary involvement – severe pulmonary hypertension and valvular abnormalities – is infrequently reported. This case reinforces the expanding phenotypic spectrum of BBS and emphasizes the need for multidisciplinary evaluation to identify such atypical features.
CASE REPORT
A male in his mid-20s presented with progressive breathlessness, bilateral pedal edema, and abdominal distension over several weeks. There is no medical history of poor scholastic performance. There is no additional family history or genetic information available.
Clinical findings
The patient exhibited dysmorphic features, including rounded facies, broad nasal bridge, short neck, upward-slanting palpebral fissures, micrognathia with underdeveloped chin, flat facial profile, and low-set ears in Figures 1 and 2. Gynecomastia and underdeveloped secondary sexual characteristics were noted, which are apparent in Figure 3, including absence of facial and body hair, Tanner stage 3 development, and bilateral cryptorchidism. Syndactyly was present in both feet, with soft-tissue webbing between the second and third toes [Figure 4]. Radiographic evaluation confirmed the absence of bony fusion, indicating soft-tissue syndactyly [Figure 5]. Anthropometry showed short stature (145 cm) and body mass index 28.5, with central obesity (waist–height ratio 0.58). Systemic examination revealed elevated jugular venous pressure (JVP), bilateral pitting pedal edema, basal crepitations, and abdominal distension with an umbilical hernia.
Investigations
Investigations revealed that blood parameters and hormone profiles, which are illustrated in Table 1. Electrocardiogram demonstrated incomplete right bundle branch block, left anterior hemiblock, and P pulmonale. Echocardiography showed a myxomatous mitral valve with anterior mitral tip prolapse, along with severe tricuspid regurgitation and severe pulmonary hypertension. Ultrasound examination of the abdomen revealed the absence of the right kidney, suggestive of right renal agenesis. Ophthalmological examination was normal, with no evidence of rod-cone dystrophy.
| No. | Investigation | Value | Normal value |
|---|---|---|---|
| 1. | HbA1c | 5.88 | <5.7 |
| 2. | Cortisol | 13.12 | 6–18 ug/dL |
| 3. | FSH | 25.18 | 4.5–12.44 mIU/mL |
| 4. | LH | 17.63 | 1.7–8.6 mIU/mL |
| 5. | Testosterone | 2.67 | 2.9–8.89 (Male - 20–40 years) |
| 6. | TSH | 0.79 | 0.27–4.2 uIU/mL |
| 7. | Triglyceride | 238 | <150 mg/dL |
| 8 | Total cholesterol | 233 | <200 mg/dL |
| 9 | HDL | 35 | >40 mg/dL |
| 10 | LDL | 138 | <100 mg/dL |
HbA1c: Glycated hemoglobin, FSH: Follicle-stimulating hormone, LH: Luteinizing hormone, TSH: Thyroid-stimulating hormone, HDL: High-density lipoprotein, LDL: Low-density lipoprotein.
Diagnostic challenges
Limited access to genetic testing due to financial constraints and availability. Diagnosis relied entirely on clinical criteria.
Different diagnosis
Given the multisystemic involvement, the initial differential diagnoses included Alstrom syndrome, McKusick– Kaufman syndrome, Joubert syndrome, and Senior–Loken syndrome.
The combination of renal anomaly, hypogonadism, characteristic facies, short stature, and cardiopulmonary findings met the established clinical diagnostic criteria for BBS (four primary features and at least two secondary features), as illustrated in Table 2.[3-5]
| Features | Frequency (%) |
|---|---|
| Primary features | |
| Rod-cone dystrophy | 93 |
| Polydactyly | 63–81 |
| All four limbs: 21 | |
| Upper limbs only: 9 | |
| Lower limbs only: 21 | |
| Obesity | 72–92 |
| Genital anomalies | 59–98 |
| Renal anomalies | 53 |
| Learning difficulties | 61 |
| Secondary features | |
| Speech delay | 54–81 |
| Developmental delay | 50–91 |
| Diabetes mellitus | 6–48 |
| Dental anomalies | 51 |
| Congenital heart disease | 7 |
| Brachydactyly/syndactyly | 46–100/8–95 |
| Ataxia/poor coordination | 40–86 |
| Anosmia/hyposmia | 60 |
Treatment
The patient was initiated on furosemide (Lasix) with 40 mg bd for symptomatic management of fluid overload. He responded well with a reduction in edema and dyspnea. Multidisciplinary evaluation was initiated with endocrinology, cardiology, and nephrology input. Hormonal replacement therapy and long-term follow-up were planned. The patient was discharged on a diuretic (torsemide 10 mg od), aspirin 75 mg, and atorvastatin 20 mg. Genetic counseling was advised, though genetic testing was not pursued due to resource constraints.
Outcome and follow-up
The patient showed symptomatic improvement with diuretic therapy. He was advised to undergo regular follow-up for monitoring of cardiac function, renal parameters, and endocrine health. Hormonal therapy was initiated, and he remains under evaluation for long-term reproductive and renal management. Genetic evaluation remains pending due to financial constraints. On follow-up visit, the patient was asymptomatic, and no adverse reactions to the therapeutic intervention were observed.
DISCUSSION
This case highlights the value of clinical diagnostic criteria in identifying BBS in resource-limited settings where genetic testing is inaccessible. It demonstrates an uncommon adult presentation with significant cardiopulmonary involvement, expanding awareness of the syndrome’s phenotypic variability. The multidisciplinary evaluation strengthens the accuracy and relevance of the clinical diagnosis. The absence of genetic confirmation limits definitive diagnosis and restricts a deeper understanding of the underlying molecular variant. Long-term follow-up data are incomplete, preventing assessment of disease progression and therapeutic impact. Being a single case, generalizability is inherently limited.
BBS is named after Georges Bardet and Arthur Biedl. Laurence–Moon-BBS is no longer considered a valid term, as patients of Laurence and Moon had paraplegia but no polydactyly and obesity, which are the key elements of the BBS.[3,4] The frequency of the syndrome is estimated to be 1:1,60,000. Less than 15 cases have been reported from India. BBS is a genetically heterogeneous ciliopathy with diverse phenotypic expression. At least 20 BBS genes have already been identified, and all of them are involved in primary cilia functioning.[2] Diagnosis is established by identifying a combination of major and minor criteria, Table 2, in a resource-limited setting.[1,3-5] Although retinal dystrophy is a hallmark feature, its absence does not exclude the diagnosis. This case was notable for cardiopulmonary involvement, including severe pulmonary hypertension and valvular dysfunction, which are less frequently described but clinically significant. The presence of right renal agenesis, hypogonadism, cryptorchidism, and typical facies met the clinical criteria for BBS. Timely diagnosis enabled appropriate symptomatic management.
CONCLUSION
Bardet–Biedl syndrome can be effectively diagnosed using clinical criteria in resource-limited settings where genetic testing is unavailable. This case highlights an unusual adult presentation with significant cardiopulmonary involvement, expanding the known phenotypic spectrum of the disease. Early recognition and a multidisciplinary approach are essential for timely management and prevention of complications.
Author contributions:
NS: Contributed to study conceptualization, drafting of the manuscript, data collection, and patient management, and approved the final version of the manuscript for publication; GR: Contributed to manuscript preparation and study visualization, supervised the overall study, participated in project administration, and was involved in reviewing and editing the manuscript; AS: Contributed to manuscript preparation was responsible for study methodology and software-related data, performed formal analysis, and was involved in reviewing and editing the manuscript; VS and ST: Were responsible for study resources, investigation, and data curation; NB: Contributed to study conceptualization and visualization.
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understands that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.
Financial support and sponsorship: Nil.
References
- New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J Med Genet. 1999;36:437-46.
- [CrossRef] [PubMed] [Google Scholar]
- Phenotypic variability of Bardet-Biedl syndrome: focusing on the kidney. Pediatr Nephrol. 2012;27:7-15.
- [CrossRef] [PubMed] [Google Scholar]
- Unusual presentation of multiple endocrine neoplasia type 2A in a patient with the C634R mutation of the RET-protooncogene. Ann Endocrinol (Paris). 2008;69:523-5.
- [CrossRef] [PubMed] [Google Scholar]