Table 4.

Disorders to Consider in the Differential Diagnosis of Alström Syndrome

DisorderGene(s)MOIClinical Features
Overlapping w/Alström syndromeDistinguishing from Alström syndrome (AS)
Bardet-Biedl syndrome (BBS)>21 genes 1AR 2
  • Rod-cone dystrophy
  • Central obesity
  • Hypogonadism
  • Renal dysfunction
  • Older mean age of onset of visual problems in BBS (8.5 yrs in BBS vs birth - 2 yrs in AS)
  • Polydactyly is common in BBS (not described in AS).
  • Cognitive impairment is common in BBS (normal intelligence in most persons w/AS).
  • Hearing problems are infrequent (~5%) in BBS.
  • Diabetes mellitus is less frequent (5%-10%) in BBS.
Achromatopsia (ACH) ATF6
CNGA3
CNGB3
GNAT2
PDE6C
PDE6H 		AR
  • Infantile nystagmus
  • Photophobia
  • Severely ↓ visual acuity
  • Poor or no color discrimination
  • Only the retina is affected in ACH. 3
Retinal findings:
  • Common in ACH; not reported in AS: central outer retinal atrophy/cavitation
  • Common in AS; less common in ACH: retention of central inner retinal layers (foveal immaturity)
Absent in ACH:
  • Cardiomyopathy, obesity, SNHL, T2DM, liver disease, & renal dysfunction
Leber congenital amaurosis / early-onset severe retinal dystrophy (LCA/EOSRD)>30 genes 4AR
AD
  • Retinal degeneration
  • ↓ visual acuity
  • Onset typically in 1st yr of life
  • Nystagmus
  • Photophobia
  • Absence of other organ system involvement in LCA/EOSRD
  • Characteristic oculo-digital sign (repeated eye rubbing, poking, & pressing of eyes) in LCA/EOSRD
Early-onset dilated cardiomyopathy (DCM) (See Dilated Cardiomyopathy Overview.)>25
  • Dilated cardiomyopathy
  • Renal dysfunction (in syndromic forms due to mt defect)
Skeletal muscle disease w/↑ creatine kinase in most syndromic forms of DCM (not observed in AS)
Mitochondrial disorders 5See footnote 5.AR
AD
Mat
  • Cardiomyopathy
  • Sensorineural deafness
  • Optic atrophy
  • Pigmentary retinopathy
  • Diabetes mellitus
  • CNS involvement & muscle weakness may occur in mt disorders (not reported in AS).
  • Late-childhood or adulthood presentation in mt disorders (vs AS, which usually presents in 1st yr of life)

AD = autosomal dominant; AR = autosomal recessive; AS = Alström syndrome; MOI = mode of inheritance; Mat = maternal; mt = mitochondrial; SNHL = sensorineural hearing loss

1.

At least 21 genes are associated with BBS: BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, CEP290, WDPCP, SDCCAG8, LZTFL1, BBIP1, and IFT27.

2.

In some families, pathogenic variants in more than one BBS-related gene may result in a clinical phenotype of BBS. However, such families are difficult to identify and by previous estimations may account for less than 10% of all BBS.

3.
4.

To date, variants in 24 genes account for 70%-80% of individuals with LCA/EOSRD (see Leber Congenital Amaurosis / Early-Onset Severe Retinal Dystrophy Overview: Table 2).

5.

Mitochondrial disorders are a heterogeneous group of complex disorders that may be caused by pathogenic variants in mitochondrial DNA or nuclear DNA (see Mitochondrial Disorders Overview).

From: Alström Syndrome

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