Paula and Bobby
Parents of Lillie
What is Trichorhinophalangeal syndrome?
Trichorhinophalangeal syndrome is a very rare, inherited genetic syndrome that affects multiple parts of the body.
The main features and symptoms of the syndrome are craniofacial and skeletal abnormalities.
Trps I TRPS1 TRPS3
What gene changes cause Trichorhinophalangeal syndrome?
Mutations to the TRPS1 gene on chromosome 8 are known to cause the syndrome. The syndrome is inherited in an autosomal dominant pattern.
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.
A few cases of the symptom have been identified as the result of a new gene mutation. 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.
What are the main symptoms of Trichorhinophalangeal syndrome?
The main symptoms, which may vary in their severity between individuals, include hypermobility and abnormalities relating to the bones and joints.
Physical conditions of the syndrome include problems affecting the skin, hair, teeth, nails and sweat glands. Many individuals have sparse, scalp hair and by the time they reach puberty most males with the syndrome are completely bald.
Facial characteristics of the syndrome include a rounded nose, long, flat philtrum, a thin and long upper lip, large ears, small lower jaw, thin eyebrows, sparse eyelashes, a triangular face and a short stature. A curving of the fifth finger is also common.
Possible clinical traits/features:
Flat capital femoral epiphysis, Fine hair, Cone-shaped epiphyses of the proximal phalanges of the hand, Cone-shaped epiphyses of the middle phalanges of the hand, Concave nail, Ivory epiphyses of the distal phalanges of the hand, Coxa magna, Delayed eruption of teeth, Delayed skeletal maturation, Dental malocclusion, Deep philtrum, Avascular necrosis of the capital femoral epiphysis, Carious teeth, Arthralgia, Accelerated bone age after puberty, Abnormally low-pitched voice, Hyperlordosis, Short stature, Intellectual disability, Macrotia, Sparse lateral eyebrow, Leukonychia, Infantile muscular hypotonia, Narrow palate, Long philtrum, Microdontia, Micrognathia, Osteopenia, Pear-shaped nose, Pectus carinatum, Pes planus, Osteoarthritis, Autosomal dominant inheritance, Protruding ear, Slow-growing hair, Thin nail, Recurrent respiratory infections, Short metatarsal, Short metacarpal, Thin upper lip vermilion, Sparse hair, Swelling of proximal interphalangeal joints, Chin with horizontal crease, Scapular winging,
How does someone get tested for Trichorhinophalangeal syndrome?
The initial testing for Trichorhinophalangeal 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 Trichorhinophalangeal syndrome
Trichorhinophalangeal syndrome (TRPS) type I is characterized by distinctive skeletal findings (early-onset hip dysplasia; short stature; brachydactyly, cone-shaped epiphyses), facial features (large nose with broad ridge and tip; underdeveloped alae; long philtrum; and large prominent ears); and ectodermal features (sparse hair). The autosomal dominant disorder is caused by heterozygous mutations in the TRPS1 gene.
There are considerable similarities to Langer-Giedion syndrome (also known as Trichorhinophalangeal syndrome type II). Both conditions may be caused by small deletions of the long arm of chromosome 8 (see Goldblatt et al., 1986, and Fryns et al., 1986); however Ludecke et al., (1995) presented data suggesting the TRP gene mapped more than 1,000 kb proximal to the putative multiple exostoses gene, and that both genes were deleted in Langer-Giedion syndrome.
They also suggested that the genes responsible for intellectual disability map outside this interval because Langer-Giedion patients with very small deletions are mentally normal, whereas TRP type 1 patients with large deletions extending more centromeric have intellectual disability.
Sugio and Kajii (1984) reported a dominant family they thought represented Ruvalcaba syndrome, and Niikawa and Kamei (1986) reported a similar case; however, the latter authors thought these cases had a form of Trichorhinophalangeal syndrome (designated TRP type III). Mutations in TRPI tend to be nonsense mutations, whereas those in TRPIII are missense (Kobayashi et al., 2002), dominant negative mutations (Ludecke et al., 2001). This gene was deleted in all cases with Langer-Giedion syndrome.
Sasaki et al., (1997) reported an 11-year-old girl with a 4 Mb deletion of 8q associated with a paracentric inversion with features of TRP type 1. She did not have intellectual disability. Postaxial polydactyly was present in the hands.
Giedion et al., (1998) reviews the appearance and evolution of cone-shaped epiphyses in Trichorhinophalangeal syndromes type I and II, and cartilage-hair hypoplasia.
Haan et al., (1989) reported a family where a paracentric inversion of chromosome 8 was segregating. Affected individuals had features both of Trichorhinophalangeal syndrome and branchio-oto dysplasia, and it was suggested that the gene for the latter was at either of these breakpoints. Gu et al., (1996) reported further molecular studies on this family indicating a megabase deletion.
Momeni et al., (2000) reported mutations in a gene coding a protein with two potential nuclear localizing signals and an unusual combination of different zinc-finger motifs, including IKAROS-like and GATA-binding sequences, in Trichorhinophalangeal syndrome type I.
Wuyts et al., (2002) reported a boy with multiple exostoses, hypertrichosis, intellectual disability, and epilepsy due to a de novo deletion on chromosome 8q24. Molecular analysis revealed the deletion overlapped with Langer-Giedion syndrome and involved the EXT1 gene and additional genes located distal to EXT1, but probably not encompassing the TRPS1 gene located proximal to EXT1.
Two sibs and their mother were reported by Sidler et al. (2012) with TRPS type 1. The two sibs showed intellectual disability, and all had a TRPS1 mutation. This mutation (p.Arg965His) has previously been reported but without intellectual disability.
A family reported by Hufeland et al., (2014) had four members all with a Perthes-like hip dysplasia. A novel mutation in exon 6 was found.
Gilman et al., (2017) described two unrelated male patients with trichorhinophalangeal type 1 syndrome and avascular necrosis of the femoral head (Legg-Calvé-Perthes disease).
* This information is courtesy of the L M D.
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