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Floating Harbor syndrome

This is part of Rare diseases.

Diagnosis: Floating Harbor syndrome

Synonyms: Pelletier-Leisti syndrome

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Publication date: 2012-06-25
Version: 2.0

ICD 10 code

Q87.8

The disease

Floating Harbor syndrome is characterised by delayed skeletal maturation, short stature, typical facial features and delayed speech development.

The syndrome is named after the two hospitals at which children with these symptoms were first described in 1973: G. Pelletier and M. Feingold worked at Boston Floating Hospital, and J. Leisti and associates worked at Harbor General Hospital in Los Angeles.

Occurrence

It is not known how many people in Sweden have Floating Harbor syndrome. Fewer than 50 cases are described in the international medical literature, but the syndrome is most likely more prevalent than the figure indicates. Approximately 10 people in Sweden have been diagnosed with the syndrome.

Cause

Floating Harbor syndrome is caused by a mutation in a gene on chromosome 16 (16p11.2). This gene, known as SRCAP, governs the production (codes for) the protein SRCAP, which is one of several proteins that activate CBP (cyclic AMP-binding protein). Mutations in the CBP gene, which regulates the production of CBP, causes another disorder: Rubinstein-Taybi syndrome. Separate information on Rubinstein-Taybi syndrome is available in the rare disease database of the Swedish Board of Health and Welfare.

The fact that CBP activity is affected by SRCAP is considered a likely explanation of why the symptoms of Floating Harbor syndrome resemble those of Rubinstein-Taybi syndrome.

Heredity

The inheritance pattern of Floating Harbor syndrome is autosomal dominant. This means that one of the parents has the disease, and so has one normal gene and one mutated gene. Sons and daughters of this parent have a 50 per cent risk of inheriting the disease. Children who do not inherit the mutated gene do not have the disease and do not pass it down.

Figure: Autosomal dominant inheritance

Although there are cases in which several members of the same family have the syndrome, most cases are caused by a new mutation. This means that a genetic change occurs for the first time in the individual, and is not inherited from either parent. Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult with this mutation risks passing on the mutated gene to his/her children.

Symptoms

Children with the syndrome are shorter and weigh less than normal at birth. Characteristic facial features can sometimes be distinguished at birth but become more evident at around the age of three or four. The face is triangular, the nose prominent, the lips thin and the distance between nose and lips (the philtrum) short. The eyes are often deep-set and the ears rotated posteriorly. Fingers and toes may be shorter than normal and the little finger crooked (clinodactyly). The skull may have a triangular shape (trigonocephaly) as the middle (metopic) suture along the midline of the forehead, from the fontanel to the bridge of the nose, has closed prematurely.

These children very often have difficulties sucking, managing to eat only for short periods, and they often vomit copiously during meals. Feeding takes a long time and these children do not gain weight as expected.

Skeletal maturity is often substantially delayed. By the time they are seven the skeletal growth and bone maturity of these children may be up to four years delayed, and therefore they are shorter than their peers. Motor skills may also develop late, which means that these children learn to walk later than others. Many have unstable joints, the joints of the hip being particularly affected.

Children have major problems forming sounds and expressing themselves, which contributes to delayed speech development, although their comprehension skills are normal. During childhood the voice is often rather shrill. Bite abnormalities can occur and there are reports of some abnormalities in tooth enamel.

Heart defects may also be identified, the most common being constriction of the pulmonary valve (pulmonary stenosis).

Abnormalities in the appearance of nails as well as excessive hair growth may also occur.

Many people with the syndrome are also thought to be sensitive to gluten, a protein present in wheat, rye and barley. This intolerance (celiac disease) may damage the small intestine. The symptoms are poor weight gain, vomiting and diarrhoea or constipation, fatigue and irritability. All children with this syndrome should be examined for celiac disease.

Abnormalities in the urinary tract may present so that, for example, the urethra opens on the underside of the penis (hypospadia) or kidneys are positioned abnormally.

Approximately 50 per cent of individuals with Floating Harbor syndrome have mild cognitive impairment. Individuals with cognitive impairment require more time to understand and learn new skills. They may also have difficulties organising new information, adapting to new situations, and seeing how things or events relate to each other.

Diagnosis

The diagnosis is based on short stature, distinct physical features, and delayed speech and language development.

DNA-based diagnosis is often possible. Foetal diagnosis and embryo diagnosis are possible if the mutation in the family has been identified. At the time of diagnosis, the family should be offered genetic counselling.

Treatment/interventions

There is no cure for Floating Harbor syndrome, and interventions are directed at treating the symptoms. If the child has an abnormally shaped skull, surgery is required at an early age to open the sutures of the skull so that the brain has room to grow and the head can develop more normally. Many children with the syndrome have metal springs inserted surgically under the skin between the bony plates of the skull.

Delayed weight gain and vomiting can cause great anxiety to the parents and it is important that they receive practical and psychological support. A dietician can provide information on different foods and dietary supplements, and a speech therapist offers advice on how to stimulate oral motor skills in order to improve the processes of chewing and swallowing. For some of the smallest children tube feeding through the nose may be necessary.

Severe narrowing of the pulmonary valve may require immediate intervention, either using balloon dilation (angioplasty) or surgery. In less acute cases, surgery or other treatment may be carried out some time during the first few years of the child’s life.

Abnormalities of the urinary tract and genitals must be investigated. Investigations and treatment may be carried out at clinics for paediatric surgery.

Growth deficiency can sometimes be treated with growth hormones.

In cases of celiac disease the child’s diet should be gluten-free, containing no wheat, rye or barley. A gluten-free diet can usually contain oats while wheat, rye and barley can be replaced with gluten-free flour and grains. The gluten-free diet is a life-long necessity.

It is important that children have contact with the dental services from an early age for assessment, treatment and information about oral health. Additional preventive care may also be necessary. Abnormalities in dental alignment may require dental braces. If the individual has undergone heart surgery, for example heart valve replacement, antibiotics may be required before dental procedures which can cause bleeding. This treatment will prevent bacteria from the mouth from causing cardiac infections (endocarditis).

In order to stimulate development and compensate for disabilities some children will need habilitation support. Early contact should then be established with a habilitation team, which includes professionals with special expertise in how disability affects everyday life, health and development. Support and treatment take place within the medical, educational, psychological, social and technical fields. Help includes assessment, treatment, the provision of aids, information on the specific disability, and counselling. It may also include information about support offered by the local authority as well as advice on the way accommodation and other environments can be adapted to the child’s needs. Parents and siblings can also receive support. The family may also need help coordinating interventions.

Play stimulates and gives the child practice in speaking, language and communication. In order to aid development as much as possible the child’s linguistic and communication abilities are assessed. Educational and linguistic support are then adjusted to the individual child’s requirements and developmental level. Many children need to be given an early opportunity to communicate using alternative and complementary methods of communication (augmentative and alternative communication – AAC).

Some children require contact with a physiotherapist for an assessment of their motor skills and possible treatment.

The measures focus on existing needs, may vary over time and occur in collaboration with individuals close to the child.

Children and young people of short stature should be treated in a way appropriate to their age and in the same way as their same-age peers. Even when they are very young these children may be aware that they are shorter than their friends of the same age. Some may require continued psychological support through childhood. Having been allowed to be like other children, and not to have been overprotected, are important for developing good self-esteem in adulthood. Children with the syndrome and their families may find it very meaningful to meet other people in the same situation.

Adults with the syndrome require continued habilitation and support, adapted to their individual, daily needs. This may take the form of support and care in accommodation offering specialist services and daily activities.

Practical advice

There are gluten-free products, including flours, crispbread, biscuits and pasta. Potato flour, maize and rice flour, buckwheat, millet, quinoa and polenta (ground maize) are examples of naturally gluten-free foodstuffs.

National and regional resources in Sweden

Diagnosis and treatment take place at regional hospital paediatric clinics.

Resource personnel

Professor of Paediatrics Sten Ivarsson, Research Centre for Paediatric Endocrinology, CRC, Lund University, Skåne University Hospital, SE-205 02 Malmö, Sweden. Tel: +46 40 39 11 12, email: stenanders.ivarsson@gmail.com.

Courses, exchanges of experience, recreation

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Organizations for the disabled/patient associations

FUB, The Swedish National Association for Children, Young People and Adults with Intellectual Disabilities, Gävlegatan 18 C, Box 6436, SE-113 82 Stockholm, Sweden. Tel: +46 8 508 866 00, fax: +46 8 508 866 66, email: fub@fub.se, www.fub.se.

The Association for Individuals with Growth Restriction Disorders, DHR, email: fkv@telia.com, www.fkv.se

The Swedish Celiac Disease Association, Västra vägen 5B, SE-169 61 Solna, Sweden. Tel: +46 8 730 05 01, email: info@celiaki.se, www.celiaki.se.

There is an international association for people with Floating Harbor syndrome, with families from about ten countries. See www.floatingharborsyndromesupport.com, email: littlefock@gmail.com.

Courses, exchanges of experience for personnel

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Research and development (R&D)

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Information material

An information leaflet on Floating Harbor syndrome summarising the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2012-2-19). Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.

Literature

Arpin S, Afenjar A, Dubern B, Toutain A, Cabrol S, Héron D. Floating-Harbor syndrome: report on a case in a mother and daughter, further evidence of autosomal dominant inheritance. Clin Dysmorphol 2012; 21: 11-4.

Bastaki L, El-Nabi MM, Azab AS, Gouda SA, Al-Wadaani AM, Naguib KK. Floating-Harbor syndrome in a Kuwaiti patient: a case report and literature review. East Mediterr Health J 2007; 13: 975-979.

Feingold M. Thirty-two year follow-up of the first patient reported with the Floating-Harbor syndrome. Am J Med Genet A 2006 1; 140: 782-784.

Hood RL, Lines MA, Nikkel SM, Schwartzentruber J, Beaulieu C, Nowaczyk MJ et al. Mutations in SRCAP, encoding SNF2-related CREBBP activator protein, cause Floating-Harbor syndrome. Am J Hum Genet 2012; 90: 308-313.

Ioan DM, Fryns JP. Floating-Harbor syndrome in two sisters: autosomal recessive inheritance or germinal mosaicism? Genet Couns 2003; 14: 431-433.

Lacombe D, Patton MA, Elleau C, Battin J. Floating-Harbor syndrome: description of a further patient, review of the literature, and suggestion of autosomal dominant inheritance. Eur J Pediatr 1995; 154: 658-661.

Leisti J, Hollister DW, Rimoin DL. The Floating-Harbor syndrome. Birth Defects Orig Artic Ser 1975; 11: 305.

Pelletier G, Feingold M. 1973. Case report 1. In: Bergsma D, editor. Syndrome identification. Vol 1. White plains, NY: National Foundation-March of Dimes, pp 8-9.

Peñaloza JM, García-Cruz D, Dávalos IP, Dávalos NO, García-Cruz MO, Pérez-Rulfo D et al. A variant example of Floating-Harbor syndrome? Genet Couns 2003; 14: 31-37.

Robinson PL, Shohat M, Winter RM, Conte WJ, Gordon-Nesbitt D, Feingold M et al. A unique association of short stature, dysmorphic features, and speech impairment (Floating-Harbor syndrome). J Pediatr 1988; 113: 703-706.

White SM, Morgan A, Da Costa A, Lacombe D, Knight SJ, Houston SJ et al. The phenotype of Floating-Harbor syndrome in 10 patients. Am J Med Genet A 2010; 152A: 821-829.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: floating-harbor syndrome

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Professor Sten Ivarsson, Skåne University Hospital, Malmö.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Publication date: 2012-06-25
Version: 2.0
Publication date of the Swedish version: 2012-05-16

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.