Table 2.

Other Genes of Interest in the Differential Diagnosis of Floating-Harbor Syndrome (FHS)

Gene(s) 1Differential DisorderMOIClinical Features of Differential Disorder
Overlapping w/FHSDistinguishing from FHS
CCDC8
CUL7
OBSL1 		Three M syndrome AR
  • Triangular face
  • Short 5th fingers
  • Bone age may be slightly delayed.
  • Males may have hypospadias.
  • Severe pre- & postnatal growth restriction (final height 5-6 SD below mean; i.e., 120-130 cm)
  • Relatively large head, hypoplastic midface, thick eyebrows, fleshy nasal tip, long philtrum, prominent mouth & lips, pointed chin
  • Normal intelligence
  • Absence of language impairment
  • Characteristic radiologic findings
  • Short broad neck, prominent trapezii, deformed sternum, short thorax, square shoulders, winged scapulae, & hyperlordosis, prominent heels, loose joints
  • Hypogonadism in males
CREBBP
EP300 		Rubinstein-Taybi syndrome AD
  • Facial features (e.g., low-hanging columella)
  • Broad or angulated thumbs
  • 5th-finger clinodactyly
  • Short stature
  • Round face, downslanted palpebral fissures, small mouth opening
  • Severe intellectual disability
  • Normal bone age
  • Cardiac malformations
FOXP2 FOXP2 speech and language disorders See footnote 2.
  • Dysarthria
  • Hypernasality
  • Severe expressive & receptive language & literacy impairments
Absence of:
  • Short stature
  • Delayed bone age
  • FHS characteristic facies
  • Aggression in childhood

Multiple etiologies 3

Silver-Russell syndrome
(SRS)		See footnote 3.
  • Pre- & postnatal growth restriction
  • Expressive language impairment (much more severe in FHS than in SRS)
  • Body asymmetry
  • Café au lait macules
  • Blue sclera
  • Absence of FHS characteristic facial features & thumb anomalies

AR = autosomal recessive; MOI = mode of inheritance; SD = standard deviation(s); SRS = Silver-Russell syndrome

1.

Genes are listed in alphabetic order.

2.

Recurrence risk for sibs of proband with a FOXP2 speech and language disorder depends on the causative genetic alteration.

3.

Silver-Russell syndrome (SRS) has multiple etiologies including: epigenetic changes that modify expression of genes in the imprinted region of chromosome 11p15.5, maternal UPD7, and (infrequently) autosomal dominant or autosomal recessive inheritance. When a proband has SRS as the result of paternal hypomethylation at IC1 or maternal UPD7, both parents are predicted to be unaffected, the risk to the sibs is not increased over that of the general population, and the risk to offspring is probably low.

From: Floating-Harbor Syndrome

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