Table 2.

Disorders to Consider in the Differential Diagnosis of Hand-Foot-Genital Syndrome (HFGS)

Clinical Features Overlapping w/HFGSDifferential Diagnosis
Disorder		Gene(s) /
Genetic Mechanism		MOIClinical Features of Differential Diagnosis Disorder Distinguishing It from HFGS
Thumb hypoplasia, often in addition to other anomalies Fanconi anemia 21 genesAR
AD
XL
  • Bone marrow failure
  • ↑ risk of malignancy
Rothmund-Thomson syndrome RECQL4 AR
  • Rash, poikiloderma
  • Cataracts
  • ↑ risk of malignancy
Holt-Oram syndrome TBX5 ADCardiac malformation
Lacrimo-auriculo-dento-digital syndrome (OMIM 149730) FGFR3
FGF10
FGFR2 		AD
  • Characteristic facial features
  • Dental anomalies
Nager syndrome (OMIM 154400) SF3B4 ADCharacteristic facial features w/ear anomalies
Townes-Brocks syndrome SALL1 ADImperforate or stenotic anus
SALL4-related disorders (incl Duane-radial ray syndrome & acro-renal-ocular syndrome) SALL4 AD
  • Radial ray malformation
  • Duane anomaly
Incomplete müllerian fusion &/or longitudinal vaginal septum
Bardet-Biedl syndrome ≥19 genesAR
  • Obesity
  • Rod-cone dystrophy
Beckwith-Wiedemann syndrome 11p15 epigenetic & genomic alterations 1See
footnote
1.		Somatic overgrowth
Fraser syndrome (OMIM PS219000) FRAS1
FREM2
GRIP1 		AR
  • Ocular involvement
  • Ear anomalies
Meckel syndrome (OMIM PS249000)~13 genesAR
  • Renal cystic dysplasia
  • Biliary abnormalities & liver fibrosis
  • Encephalocele

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; XL = X-linked

1.

Beckwith-Wiedemann syndrome is associated with abnormal regulation of gene transcription in two imprinted domains on chromosome 11p15.5. Most individuals with BWS are reported to have normal chromosome studies or karyotypes. Approximately 85% of individuals with BWS have no family history of BWS; approximately 15% have a family history consistent with parent-of-origin autosomal dominant transmission.

From: Hand-Foot-Genital Syndrome

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