Floating–Harbor syndrome

Floating–Harbor syndrome, also known as Pelletier–Leisti syndrome, is a rare disease with fewer than 50 cases described in the literature. It is usually diagnosed in early childhood and is characterized by the triad of proportionate short stature with delayed bone age, characteristic facial appearance, and delayed speech development. Although its cause is unknown, it is thought to result from genetic mutation, and diagnosis is established by the presence of a heterozygous SRCAP mutation in those with clinical findings of FHS.

Signs and symptoms

Below are the common clinical features of those diagnosed with Floating–Harbor syndrome. Patients will show varying degrees of some or all FHS symptoms. Facial abnormalities are the most defining aspects of those diagnosed with this disease.

Cardinal facial features

Triangular face

Deep-set eyes

Short philtrum

Wide mouth with a thin vermilion border of the upper lip

Long nose with a narrow bridge and broad, bulbous base

Low-set ears

Voice quality and language

Dysarthria and verbal dyspraxia with phoneme imprecision

Hypernasality

High-pitched voices

Severe receptive and expressive language impairment across all domains of function

Bodily features

Significant delay in bone age (-2 SD or greater) with normalization between 6–12 years old

Skeletal anomalies: brachydactyly, broad fingertips or clubbing, clinodactyly, short thumbs, prominent joints, clavicle abnormalities

Short adult stature: for females, maximum height was at the 20th percentile; for males, the maximum height was at the 25th percentile, though male height varied more widely

The differential diagnosis of broad thumbs includes Rubinstein-Taybi syndrome, where they are a cardinal feature. FHS is also in the differential, which logically agrees with the thought that the disease is a result of a mutation in SRCAP, as this gene interacts with CBP.

Behavior

Tantrums during infancy

Attention deficit-hyperactivity disorder (ADHD) during school years: impulsivity, inattention, restlessness

Unpredictable, aggressive outbursts

Autistic spectrum disorder (one case)

Asperger syndrome (one case)

Obsessive compulsive disorder (two cases)

Other observations

Intellectual disability: in all cases each individual showed a varying degree of intellectual impairment and learning disability, ranging from borderline normal to moderate intellectual disability

Early entry into puberty is shown in some girls, leading to menorrhagia and irregular periods

Dental problems (caries, malocclusion, dysplastic, small teeth)

Visual impairment

Mechanism

The cause of this condition is unknown but evidence of familial inheritance and sporadic genetic mutation has been linked to cases of FHS. Two possibly familial cases have been reported—one in a mother and son, and the other in a mother and daughter. This suggests an autosomal dominant inheritance but additional cases need to be investigated to establish this. Another report has suggested that the inheritance may be autosomal recessive. In all of these cases, however, the mothers and children were not similarly affected, suggesting a variable clinical expression of the syndrome.