Introduction

Floating-Harbor syndrome (FHS) is a rare genetic condition marked by proportionate short stature, delayed bone growth, delayed speech development, and distinctive facial features. The syndrome gets its name from the two hospitals where it was first identified: the Boston Floating Hospital and Harbor General Hospital in Torrance, California. FLHS is caused by mutations in the SRCAP gene, typically inherited in an autosomal dominant pattern. However, most cases arise spontaneously due to new (de novo) mutations. Management of the condition focuses on addressing symptoms and providing supportive care.^1,2

People with FHS often have distinct facial features and are born with low birth weight, but their head size is usually normal. They tend to be shorter than average and experience delayed bone growth, which typically catches up between the ages of six and 12 years old.

Children with FHS may have certain bone differences, such as short fingers and thumbs, curved fingers, prominent joints, and unusual collarbone shapes. They often face significant challenges with both understanding and using language, and their voices might sound high-pitched and nasal. Mild to moderate intellectual disabilities are also common.

Behavioural and temperamental difficulties are frequently seen in kids with FHS, but the good news is that these issues often get better as they reach adulthood. Other possible symptoms include vision problems like farsightedness or crossed eyes, hearing loss, seizures, acid reflux, kidney issues, and, in children assigned male at birth (AMAB), genital differences such as undescended testicles or abnormal urethra openings.

Understanding and supporting individuals with FHS can make a big difference in managing these various symptoms and improving their quality of life.³

Cognitive and intellectual disabilities in floating harbor syndrome

Children with FHS generally hit their motor milestones on time, but they often face mild to moderate intellectual challenges. One of the biggest obstacles for these kids is communication. They frequently experience delays in expressive language and struggle with speech, sometimes due to issues like palate immobility. It’s also common for children with FHS to have high-pitched, hypernasal voices, and many also deal with conductive hearing loss. Despite these challenges, most children with FHS can attend regular schools, where they receive individualised support to help them succeed. Importantly, they don’t typically lose the skills they acquire as they grow.^3,4

Diagnosis and assessment

FHS is often identified by a mix of distinctive physical features and developmental challenges. Some of the key facial characteristics include a triangular face, deep-set eyes, a short philtrum, and a wide mouth with a thin upper lip. The nose tends to be long with a narrow bridge and broad base, with the tissue between the nostrils hanging low. Low-set ears are also common.

People with FHS often also experience delayed bone development, which usually catches up between the ages of six and 12. Skeletal issues like short fingers, broad fingertips that can look clubbed, curved fingers, short thumbs, and prominent joints are also frequently observed. Adults with FHS typically have shorter-than-average height, ranging from 140 to 155 cm.

Speech and language development can be challenging for individuals with FHS. Many experience unclear speech and have trouble coordinating the movements needed for speaking (verbal dyspraxia). Their voices may sound high-pitched and nasal. Delays in both understanding and expressing language are common.

Intellectual abilities in individuals with FHS vary, but some degree of impairment or learning disability is always present, ranging from mild to moderate.

Diagnosing FHS involves identifying these characteristic symptoms, taking a detailed patient history, and conducting a thorough clinical evaluation, along with various specialised tests. The facial features of FHS can be subtle, especially in infants, and many of the other symptoms overlap with other conditions, making it difficult to diagnose based on clinical observations alone.

Molecular genetic testing can confirm a diagnosis of FHS by detecting mutations in the SRCAP gene, though this testing is only available through specialised laboratories. Prenatal diagnosis may also be possible for families with a known SRCAP gene mutation. This involves analyzing DNA from foetal cells obtained through procedures like amniocentesis or chorionic villus sampling (CVS). Amniocentesis involves taking a sample of the fluid surrounding the foetus, while CVS involves taking tissue samples from the placenta.

For parents with a known genetic abnormality, preimplantation genetic diagnosis (PGD) might be an option. PGD is performed on embryos created through in vitro fertilisation (IVF) to check for the same genetic abnormality. Families interested in this option should consult a certified genetics professional.^1,3

Management and intervention strategies

Treating FHS involves addressing the unique symptoms each person experiences, often requiring input from a range of specialists. This might include doctors who focus on children, nerve and brain issues, bone health, hearing and vision problems, dental care, and speech therapy. By working together, these experts can create a personalised plan to help manage the condition effectively.

Because FHS is so rare, there aren't any standard treatment guidelines. Most of what we know comes from individual case reports or small studies, so we don't have large-scale treatment trials to rely on. Such trials would be invaluable in understanding the long-term safety and effectiveness of different treatments for those with FHS.

It's crucial to start developmental support early to help children with FHS reach their full potential. Many will benefit from occupational, physical, and speech therapy. Special education and vocational training can also make a big difference. Support for parents, including counselling, is important, and genetic counselling can be helpful for families looking to understand more about the condition.

Some children with FHS have been treated with growth hormone therapy, though we don’t have a lot of data on how effective it is or what side effects it might have. If this treatment is being considered, consulting with an endocrinologist is a good step.

For other symptoms, treatment usually follows standard medical practices. For example, if a child has seizures, antiseizure medications might be prescribed. Overall, many individuals with FHS maintain good health and enjoy a good quality of life.

Key treatment points include:

• Early intervention with therapy, special education, and job training to tackle developmental challenges
• Supporting communication, possibly with sign language or other methods if needed
• Managing behaviour with strategies from a specialist, and medication if necessary
• Connecting families to support groups and resources
• Treating specific issues like vision or hearing problems, seizures, kidney issues, and dental complications according to standard medical guidelines
• Considering growth hormone therapy, though this should be done carefully with guidance from an endocrinologist
• Checking for coeliac disease if symptoms suggest it^1,3

Prognosis and long-term outlook

The long-term outlook for people with FHS can differ greatly, especially when it comes to cognitive and intellectual abilities. Some individuals may experience improvements in cognitive skills over time, especially if early intervention strategies are put in place. Intellectual disabilities in FHS can range from mild to moderate, but with the right support, many can make progress in communication and learning as they grow.

Several factors influence the prognosis for someone with FHS. The severity of the condition is a key factor – those with milder symptoms tend to do better. Early diagnosis and intervention are essential because they allow for timely treatments that help manage symptoms and support development. Ongoing support from healthcare providers, educators, and family members is crucial for improving long-term outcomes for individuals with FHS.

Summary

Floating-harbour syndrome (FHS) is a rare genetic condition that causes distinct facial features, developmental delays, and learning difficulties. Children with FHS often face challenges with speech and language, struggling to express themselves clearly. Learning difficulties vary, but with the right help, many can improve their communication and learning over time.

Doctors can confirm FHS through genetic testing, looking for changes in a specific gene. There isn't a standard treatment for FHS because it's so rare, but a team of specialists usually helps manage the symptoms. Early support like physical, occupational, and speech therapy is important to help kids with FHS develop as much as possible.

In some cases, growth hormone therapy is used to help with short stature, but it's not clear how effective it is. Despite the challenges, many people with FHS can live healthy, fulfilling lives, especially if they get the support they need early on.

The outlook for someone with FHS depends on how severe their symptoms are and how early they get help. With the right care, many people with FHS can gain some level of independence and live a good life.

FAQs

How many cases of floating-harbor syndrome are there?

This rare autosomal dominant syndrome, known for causing FGR and short stature in adulthood, has been documented in fewer than 100 patients in the literature.⁵

What is the differential diagnosis of floating-harbor syndrome?

Three M Syndrome:

Genetic Basis: Autosomal recessive disorder linked to mutations in CCDC8, CUL7, or OBSL1 genes.

Common Traits:

• Triangular-shaped face, short fifth fingers, and slight delay in bone age
• Males may exhibit hypospadias
• Marked by severe growth restriction before and after birth, leading to an adult height of 120-130 cm
• Features include a relatively large head, thick eyebrows, fleshy nasal tip, and normal cognitive abilities without language delays

Distinct Features:

• Specific radiologic characteristics like a short, broad neck, winged scapulae, and prominent heels
• Hypogonadism is often observed in males

Rubinstein-Taybi Syndrome:

Genetic Basis: Caused by mutations in the CREBBP or EP300 genes.

Common Traits:

• Similar facial features, including a low-hanging columella, broad or angled thumbs, and short stature

Distinct Features:

• Severe intellectual disabilities, normal bone age, and potential cardiac malformations set it apart from other syndromes

FOXP2 Speech and Language Disorders:

Genetic Basis: Linked to mutations in the FOXP2 gene.

Common Traits:

• Speech difficulties such as dysarthria, hyper nasality, and significant challenges in both expressive and receptive language

Distinct Features:

• No short stature, delayed bone age, or facial characteristics typically associated with Floating-Harbor syndrome

Silver-Russell Syndrome (SRS):

Genetic Basis: Multiple genetic factors can contribute to SRS.

Common Traits:

• Growth restrictions that begin before birth and continue afterwards
• Expressive language difficulties, though usually less severe than in Floating-Harbor syndrome

Distinct Features:

• Physical asymmetry, café au lait spots, blue sclera, and absence of Floating-Harbor syndrome’s facial traits and thumb abnormalities³

What causes floating-harbor syndrome?

Floating-Harbor syndrome (FHS) arises due to mutations in the SRCAP gene. This condition follows an autosomal dominant inheritance pattern, but in most instances, FHS appears spontaneously, caused by a new mutation that wasn’t inherited from either parent.¹