Paula and Bobby
Parents of Lillie
Floating-Harbor syndrome (FLHS)
What is Floating-Harbor syndrome (FLHS)?
Floating-Harbor syndrome is a genetic condition that presents with unique facial features and characteristics.
Other main symptoms include proportionate short stature, delayed bone age and delayed speech development.
It is named for the hospitals in California where it was first described.
What gene changes cause Floating-Harbor syndrome (FLHS)?
Mutations in the SRCAP gene located on chromosome 16 are responsible for the syndrome. Most cases are the result of a de novo mutation, but occasionally the syndrome may be caused by the inheritance of the deletion from one affected parent.
In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation which occurs during the reproductive process.
In the case of autosomal dominant inheritance just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.
What are the main symptoms of Floating-Harbor syndrome (FLHS)?
The symptoms of the syndrome include mild intellectual disability and delayed speech development.
In infancy individuals with the syndrome may show delayed bone age, but this usually corrects anywhere from 6-12 years of age.
Physical conditions of the syndrome include a triangular face, low hairline, deep-set eyes, long eyelashes, a large nose that becomes more prominent with age, a short philtrum and thin lips.
Individuals may also have short fingers, clubbing, a curved fifth finger and sometimes a high-pitched voice.
Possible clinical traits/features:
Cryptorchidism, Delayed skeletal maturation, Limitation of joint mobility, Deeply set eye, Conductive hearing impairment, Downturned corners of mouth, Coarctation of aorta, Clinodactyly of the 5th finger, Malformation of the heart and great vessels, Constipation, Cone-shaped epiphyses of the phalanges of the hand, Congenital posterior urethral valve, Broad columella, Expressive language delay, Smooth philtrum, Prominent nose, Brachydactyly, Camptodactyly of finger, Varicocele, Telecanthus, Triangular face, Strabismus, Short philtrum, Umbilical hernia, Mesocardia, Hypertrichosis, Hypermetropia, Malabsorption, Hypospadias, Cognitive impairment, Short stature, Underdeveloped nasal alae, Hypoplasia of penis, Hydronephrosis, Hirsutism, Autosomal dominant inheritance, Posteriorly rotated ears, Persistent left superior vena cava, Wide mouth, Recurrent otitis media, Short neck, Thin vermilion border, Trigonocephaly, Long eyelashes, Low posterior hairline, Low-set, posteriorly rotated ears, Joint laxity
How does someone get tested for Floating-Harbor syndrome (FLHS)?
The initial testing for Floating-Harbor syndrome can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Floating-Harbor Syndrome
Floating-Harbor syndrome is characterized by short stature, delayed bone age, delayed speech development, and typical craniofacial features. This autosomal-dominant syndrome is caused by mutations in the SRCAP gene. The majority of affected individuals have a de novo mutation.
This is probably a distinct, but difficult to diagnose, short stature syndrome. The first two patients were seen at the Boston Floating and Harbor General Hospitals, hence the name. In one, the birth weight was slightly reduced, but in both, subsequent height has always remained below the 3rd centile. The facial phenotype can be difficult to diagnose in young children (Hersh et al., 1998). The nose is broad, the mouth is large, and the ears are low-set and posteriorly rotated. The skull is long from front to back, and affected children have mild developmental delay, especially of language. The neck is short but with a low/normal posterior hairline. The eyes are deep-set but normally placed. Bone age is markedly delayed. Some cases in the literature are certainly doubtful (eg: case 1 of Patton et al., 1991; the case of Majewski and Lenard, 1991) - see Lipson (1991) for further comments.
All cases have been sporadic. However, Lacombe et al., (1995) reported a convincing case whose mother had some features of the condition (although the facial features in adulthood were not convincing).
Robinson et al., (1988) described further patients and provide a good review.
White et al., (2010) reported a series of 10 patients and reviewed the reported cases. They highlight the behavioral features, such as hyperactivity, short attention span and aggressive behavior; as incapacitating were the problems of speech and language.
Murray Feingold (2006) provides a 32-year follow-up on the first reported patient. At 37 years old, the patient was in good health, but with some arthritis in the hips and back. He works in a supermarket bagging groceries and can read a few words. He is short, has some ptosis, and his ears are slightly posteriorly rotated. His nasal configuration has not changed. His neck is short, and he has a low posterior hairline. His thumbs are short and broad.
Wieczorek et al., (2001) reported two convincing cases where one had only mild short stature (-2 SD) at the age of 11 years, and the other responded successfully to growth hormone therapy.
Wiltshire et al., (2005) described a patient who responded less to growth hormone treatment and who developed a tethered cord during treatment. They speculated about a relation between the growth hormone treatment and tethered cord development.
Renal abnormalities (renal cysts, hypertension) have been reported in a patient with a SRCAP mutation (Reschen et al., 2012). A long-term follow-up of a patient with a mutation was provided by Nagasaki et al., (2014).
Precocious puberty was reported in a girl by Stagi et al., (2007), and middle ear abnormalities resulting in conductive deafness by Hendrickx et al., (2010).
Chudley and Moroz (1991) and Houlston et al., (1994) reported cases with celiac disease.
Note the case reported by Yagi et al., (2016) with stippled epiphyses.
Lazebnik et al., (1996) reported a case with a tetralogy of Fallot, but no clinical photographs were published.
The diagnosis in the sibs reported by Fryns et al., (1996) is uncertain, and the same applies to the mother and offspring pair reported by Ioan and Fryns (2003). The mother and child reported by Penalozaet et al., (2003) are also in doubt.
A mother and daughter were reported by Arpin et al., (2012). No X-rays were available, and mother had in addition a seizure disorder. The facial features were unremarkable.
Ala-Mello and Peippo (1996) reported a case with a supernumerary upper incisor and an exceptionally high-pitched voice. In a follow-up study of this patient (Ala-Mello and Peippo, 2004), eventual height was calculated to be normal.
Milani et al. (2018) described a four year old female patient with Floating-Harbor syndrome associated with a novel SRCAP mutation and characterized by Perthes disease.
A patient with a 12q15-q21.1 microdeletion reported by Lopez et al., (2012) had some features of Floating-Harbor syndrome, but when other patients with that diagnosis were looked at, 12q15-q21 deletions were not found.
* This information is courtesy of the L M D.
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