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Nephrol Dial Transplant (2002) 17: 2261–2264
Teaching Point
(Section Editor: K. Kühn)
An infant with polydactyly and renal anomalies: early diagnosis
of a rare syndrome
Daniella Magen, Nathan Ish-Shalom1, Abraham Lorber2, Asaad Khoury2 and Israel Zelikovic
Pediatric Nephrology Unit and 2Pediatric Cardiology Unit, Rambam Medical Center, and 1Department of Pediatrics,
Carmel Medical Center, Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, Israel
Keywords: Bardet–Biedl syndrome; Laurence–Moon–
Biedl syndrome; non-allelic heterogeneity; pigmentary
retinopathy; postaxial polydactyly
Case
A 3-week-old male infant was referred for evaluation
of multiple congenital anomalies and failure to thrive.
He is the fourth offspring of first degree cousins of
Arab–Muslim origin. Family history was notable for
obesity, learning difficulties, reduced kidney function
and visual impairment in a 10-year-old brother. The
infant, weighing 3.3 kg, was born after an uneventful
pregnancy at full term by spontaneous delivery. On
admission he appeared malnourished and weighed
3.1 kg. No facial dysmorphism was present (Figure 1).
There was postaxial polydactyly of all four limbs
(Figures 2 and 3). Tachypnea and dyspnea were noted,
and a grade 3u6 systolic heart murmur was heard over
the entire precordium. Blood pressure was normal in
all four extremities. Examination of the external
genitalia revealed micropenis (Figure 4) and palpable
testicles of normal size. Ophthalmologic evaluation
including fundoscopy was unremarkable.
Serum blood urea nitrogen and creatinine levels
were elevated (40 and 0.9 mgudl, respectively). Other
blood chemistries were unremarkable.
Chest X-ray showed cardiomegaly. Echocardiography revealed both atrial and ventricular septal
defects, a hypoplastic aortic arch and a tubular aortic
coarctation. Abdominal sonogram revealed left renal
crossed ectopy (Figure 5). Both kidneys were small
Correspondence and offprint requests to: Daniella Magen, MD,
Pediatric Nephrology Unit, Rambam Medical Center, PO Box 9602,
Haifa 31096, Israel. Email: [email protected]
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for age, hyperechogenic, and showed no corticomedullary differentiation. Brain ultrasonography was
unremarkable.
The combination of postaxial polydactyly and renal,
cardiac and genital malformations in an offspring of
consanguineous parents, in conjunction with a sibling
suffering from obesity, renal failure, mental retardation and visual impairment, have led us to diagnose
Bardet–Biedl syndrome (BBS) in this young infant.
Discussion
BBS is a rare autosomal recessive disorder, characterized by obesity, pigmentary retinopathy, mental retardation, hypogenitalism, postaxial polydactyly and renal
malformations. Other common manifestations include
cardiac malformations, hypertension and diabetes
mellitus.
The syndrome was independently described by
Bardet and Biedl in the 1920s [1,2]. It was later
erroneously coupled with another disorder described
by Laurence and Moon, and was consequently
referred to as Laurence–Moon–Biedl syndrome.
Based on differences in clinical characteristics, BBS
and Laurence–Moon syndrome are now recognized as
separate disorders [3].
The prevalence of BBS, generally considered a rare
disorder, is 1 : 160 000 in Europe. However, its prevalence is markedly increased in highly consanguineous Arab-Bedouin communities in the Middle East
(1 : 13 500), and in Newfoundland, Canada [4].
There is considerable heterogeneity and intrafamilial
variation in the extent and severity of clinical
manifestations of BBS. Obesity, mainly of the trunk
and proximal limbs, is one of the most common
features. It develops in early childhood and is
aggravated with age. Ocular manifestations are also
2002 European Renal Association–European Dialysis and Transplant Association
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D. Magen et al.
Fig. 3. Postaxial polydactyly of both feet, with partial syndactyly of
the second and third toes of the right foot.
Fig. 1. General appearance of the infant. Subcutaneous fat tissue is
sparse. No facial dysmorphism is seen.
Fig. 4. External genitalia with micropenis.
Fig. 2. Postaxial polydactyly of both hands.
common and become apparent between the ages of 4
and 10 years. They include retinal dystrophic changes
leading to abnormal electroretinogram, decreased
night vision, reduced visual acuity and blindness at a
young age. Mild to moderate mental retardation is an
additional feature of the syndrome. The frequency of
mental retardation and its severity vary between
reports. Hypogonadism in affected males is common.
Most affected men have small external genitalia with
primary testicular failure. In females, however, hypogonadism is less frequent, and normal fertility has
An infant with polydactyly and renal anomalies
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Fig. 5. Renal sonogram showing left renal crossed ectopy, with both kidneys located in the right abdomen. The kidneys are small for age
(length 4 cm) and hyperechogenic; mild pelvic dilatation is seen.
been reported. Dysmorphism of extremities, including
postaxial polydactyly, syndactyly or brachydactyly, is
one of the earliest and most common manifestations of
BBS. Renal involvement is observed in most affected
individuals. It consists of structural and functional
abnormalities such as calyceal or pelvic dilatation,
fetal lobulation, and focal and diffuse cortical loss, as
well as tubular dysfunction, hypertension and progressive renal failure [5,6]. Cardiac anomalies in BBS
include various valvular malformations, thickening
or defects of the interventricular septum, and hypertrophic cardiomyopathy [7]. The prognosis of patients
with BBS is generally poor. Their survival and
quality of life depend on the severity of clinical
features, as well as on the quality of the medical care
they receive [8].
BBS is an autosomal recessive disorder characterized
by non-allelic heterogeneity. Genetic analysis has
mapped the disease to several independent loci, all
of which produce similar phenotypes. Linkage analysis
studies have so far identified six distinct loci responsible for the syndrome (BBS types 1 to 6, mapped to
chromosomes 11q13, 16q21, 3p, 15q22.2-q23, 2q31
and 20p12, respectively) [4,9]. To date, only three of
the six possible genes mutated in BBS have been
identified, including: BBS2, which encodes a protein of
unknown function; BBS4, which encodes a protein
with homology to O-linked N-acetyl glucosamine
transferase; and BBS6, which encodes a putative
chaperone protein [10]. The remaining three BBS
genes, as well as the biological functions of the BBS
gene products responsible for the disorder, remain to
be identified. It has been suggested that identification
of the molecular and biochemical pathways involved
in the pathogenesis of BBS may provide clues to the
mechanisms underlying common disorders such as
obesity, diabetes mellitus and mental retardation
[10,11].
Most cases of BBS are diagnosed after the first
decade of life [5]. Diagnosis in early infancy is very
rare. Delay in diagnosis is probably related to the slow
evolving nature of clinical features in this syndrome. In
our case, the constellation of clinical findings in both
infant and older sibling, combined with the family
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history of consanguinity has led to the diagnosis of
BBS in the neonatal period. Early diagnosis of BBS
may significantly improve the quality of medical care
provided to patients with this syndrome and may
increase their survival.
Teaching points
BBS is a rare genetic disorder, inherited as an
autosomal recessive trait. Since in most cases the fullblown clinical picture does not evolve before the end of
the first decade of life, diagnosis of the syndrome
during early infancy is very rare. Nevertheless, this case
illustrates that thorough clinical evaluation coupled
with awareness of this rare syndrome can lead to the
diagnosis of BBS in early life.
References
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