FLPIS
MCID: FLP001
MIFTS: 37

Filippi Syndrome (FLPIS)

Categories: Bone diseases, Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Filippi Syndrome

MalaCards integrated aliases for Filippi Syndrome:

Name: Filippi Syndrome 57 12 20 58 72 36 29 6 70
Type 1 Syndactyly-Microcephaly-Intellectual Disability Syndrome 12 20 58
Scott Craniodigital Syndrome with Mental Retardation 57 12 72
Syndactyly, Type I, with Microcephaly and Mental Retardation 57 72
Flpis 57 72
Syndactyly, Type I, with Microcephaly and Intellectual Disability 39

Characteristics:

Orphanet epidemiological data:

58
filippi syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
filippi syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Filippi Syndrome

GARD : 20 Filippi syndrome is present at birth and impacts the development of the head, face, and limbs. Signs and symptoms include a small head ( microcephaly ), webbing of the fingers and toes ( syndactyly ), intellectual disability, growth delay, and distinctive facial features (high and broad nasal bridge, thin nostrils, small chin or micrognathia, and a high frontal hairline). Other features may can include vision problems, extra fingers and toes, and seizures. Because Filippi syndrome is very rare, it is not known how this condition changes over time. Filippi syndrome is caused by a genetic variant in the CKAP2L gene and is inherited in an autosomal recessive pattern. Diagnosis is based on the symptoms, clinical exam, and may be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms.

MalaCards based summary : Filippi Syndrome, also known as type 1 syndactyly-microcephaly-intellectual disability syndrome, is related to scott bryant graham syndrome and chromosome 2q35 duplication syndrome, and has symptoms including seizures and dystonia. An important gene associated with Filippi Syndrome is CKAP2L (Cytoskeleton Associated Protein 2 Like). The drugs Paclitaxel and Cyclophosphamide have been mentioned in the context of this disorder. Affiliated tissues include tongue, and related phenotypes are intellectual disability and dysphasia

Disease Ontology : 12 A syndrome characterized by short stature, microcephaly, syndactyly, intellectual disability, pre- and postnatal growth failure, and facial dysmorphism that has material basis in homozygous or compound heterozygous mutation in CKAP2L on chromosome 2q14.1.

OMIM® : 57 Filippi syndrome is characterized by short stature, microcephaly, syndactyly, intellectual disability, and facial dysmorphism consisting of bulging forehead, broad and prominent nasal bridge, and diminished alar flare. Common features include cryptorchidism, speech impairment, and clinodactyly of the fifth finger, Some patients exhibit visual disturbances, polydactyly, seizures, and/or ectodermal abnormalities, such as nail hypoplasia, long eyelashes, hirsutism, and microdontia (summary by Hussain et al., 2014). (272440) (Updated 05-Apr-2021)

KEGG : 36 Filippi syndrome is a rare autosomal-recessive disorder characterized by mild to severe mental retardation, syndactyly of the fingers and toes, microcephaly, pre and postnatal growth retardation, and unusual facies. Syndactyly of hands and feet seems to be the hallmark of the syndrome; 3-4 finger syndactyly being the most common. The facial appearance, including prominent nasal bridge with hypoplastic alae nasi, is similar in all patients. It has been shown that loss-of-function mutations in CKAP2L are a major cause of Filippi syndrome.

UniProtKB/Swiss-Prot : 72 Filippi syndrome: A rare disorder characterized by microcephaly, pre- and postnatal growth failure, syndactyly, and distinctive facial features, including a broad nasal bridge and underdeveloped alae nasi. Some affected individuals have intellectual disability, seizures, undescended testicles in males, and teeth and hair abnormalities.

Related Diseases for Filippi Syndrome

Diseases related to Filippi Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 scott bryant graham syndrome 29.7 NT5DC4 CKAP2L
2 chromosome 2q35 duplication syndrome 10.4
3 microcephaly 10.4
4 cleft palate, isolated 9.9
5 polydactyly 9.9
6 woods syndrome 9.9
7 alacrima, achalasia, and mental retardation syndrome 9.9
8 chitayat syndrome 9.9
9 brachydactyly 9.9
10 autosomal recessive disease 9.9
11 multiple congenital anomalies/dysmorphic syndrome-intellectual disability 9.9

Graphical network of the top 20 diseases related to Filippi Syndrome:



Diseases related to Filippi Syndrome

Symptoms & Phenotypes for Filippi Syndrome

Human phenotypes related to Filippi Syndrome:

58 31 (show top 50) (show all 60)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 dysphasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002357
3 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
4 wide nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0000431
5 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
6 cryptorchidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000028
7 specific learning disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001328
8 clinodactyly of the 5th finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0004209
9 prominent nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0000426
10 underdeveloped nasal alae 58 31 hallmark (90%) Very frequent (99-80%) HP:0000430
11 wide nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0000445
12 aphasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002381
13 severe short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0003510
14 echolalia 58 31 hallmark (90%) Very frequent (99-80%) HP:0010529
15 mutism 58 31 hallmark (90%) Very frequent (99-80%) HP:0002300
16 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
17 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
18 delayed skeletal maturation 58 31 frequent (33%) Frequent (79-30%) HP:0002750
19 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
20 prominent forehead 58 31 frequent (33%) Frequent (79-30%) HP:0011220
21 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
22 downslanted palpebral fissures 58 31 frequent (33%) Frequent (79-30%) HP:0000494
23 bilateral single transverse palmar creases 58 31 frequent (33%) Frequent (79-30%) HP:0007598
24 short philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0000322
25 broad forehead 58 31 frequent (33%) Frequent (79-30%) HP:0000337
26 limitation of joint mobility 58 31 frequent (33%) Frequent (79-30%) HP:0001376
27 aplastic/hypoplastic toenail 58 31 frequent (33%) Frequent (79-30%) HP:0010624
28 broad columella 58 31 frequent (33%) Frequent (79-30%) HP:0010761
29 small nail 58 31 frequent (33%) Frequent (79-30%) HP:0001792
30 limb dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0002451
31 clinodactyly of the 5th toe 58 31 frequent (33%) Frequent (79-30%) HP:0001864
32 paraplegia 58 31 frequent (33%) Frequent (79-30%) HP:0010550
33 enlarged epiphyses 58 31 frequent (33%) Frequent (79-30%) HP:0010580
34 hypotonia 31 frequent (33%) HP:0001252
35 ventricular septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001629
36 finger syndactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0006101
37 thin vermilion border 58 31 occasional (7.5%) Occasional (29-5%) HP:0000233
38 supernumerary nipple 58 31 occasional (7.5%) Occasional (29-5%) HP:0002558
39 hypodontia 31 occasional (7.5%) HP:0000668
40 ambiguous genitalia 31 occasional (7.5%) HP:0000062
41 sparse hair 31 occasional (7.5%) HP:0008070
42 hypertrichosis 31 occasional (7.5%) HP:0000998
43 seizure 31 occasional (7.5%) HP:0001250
44 seizures 58 Occasional (29-5%)
45 muscular hypotonia 58 Frequent (79-30%)
46 visual impairment 31 HP:0000505
47 short stature 58 Frequent (79-30%)
48 microdontia 31 HP:0000691
49 growth delay 58 Frequent (79-30%)
50 postnatal growth retardation 31 HP:0008897

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
cerebellar atrophy
mental retardation
dystonic movements
dystonic tongue protrusion
more
Skeletal Skull:
microcephaly

Genitourinary Internal Genitalia Male:
cryptorchidism
ambiguous genitalia (rare)

Head And Neck Face:
short philtrum
broad forehead
hairy forehead

Head And Neck Nose:
broad nasal bridge
hypoplastic alae nasi
prominent columella

Growth Weight:
low weight

Skeletal Hands:
fifth-finger clinodactyly
bilateral cutaneous syndactyly of third and fourth fingers

Skeletal Feet:
bilateral cutaneous syndactyly of second, third, and fourth toes
hypoplasia of fifth toes (in some patients)

Head And Neck Head:
microcephaly

Head And Neck Eyes:
optic atrophy
proptosis
poor vision
retrobulbar venous varix

Growth Other:
intrauterine growth retardation
postnatal growth retardation

Cardiovascular Heart:
ventricular septal defect

Head And Neck Teeth:
small teeth
abnormally shaped teeth
hypodontia (rare)
serrated incisors (rare)

Head And Neck Mouth:
thin lips
straight mouth

Cardiovascular Vascular:
retrobulbar venous varix

Skin Nails Hair Hair:
abnormal hair growth pattern
sparse hair (rare)
hypertrichosis (rare)

Clinical features from OMIM®:

272440 (Updated 05-Apr-2021)

UMLS symptoms related to Filippi Syndrome:


seizures; dystonia

Drugs & Therapeutics for Filippi Syndrome

Drugs for Filippi Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Paclitaxel Approved, Vet_approved 33069-62-4 36314
2
Cyclophosphamide Approved, Investigational 50-18-0, 6055-19-2 2907
3 taxane
4 Albumin-Bound Paclitaxel

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Early Detection of Taxane-Induced Neuropathy in Women With Breast Cancer Completed NCT02549534

Search NIH Clinical Center for Filippi Syndrome

Genetic Tests for Filippi Syndrome

Genetic tests related to Filippi Syndrome:

# Genetic test Affiliating Genes
1 Filippi Syndrome 29 CKAP2L

Anatomical Context for Filippi Syndrome

MalaCards organs/tissues related to Filippi Syndrome:

40
Tongue

Publications for Filippi Syndrome

Articles related to Filippi Syndrome:

(show all 26)
# Title Authors PMID Year
1
Mutations in CKAP2L, the human homolog of the mouse Radmis gene, cause Filippi syndrome. 57 6 61
25439729 2014
2
Filippi syndrome: further clinical characterization. 57 6 61
18553552 2008
3
Filippi syndrome: two cases with ectodermal features, expanding the phenotype. 61 57 6
15365457 2004
4
Filippi syndrome with mild learning difficulties. 61 6 57
8867657 1996
5
Filippi syndrome: a specific MCA/MR complex within the spectrum of so called "craniodigital syndromes". Report of an additional patient with a peculiar mpp and review of the literature. 57 61
12416644 2002
6
Two brothers with atypical syndactylies, cerebellar atrophy and severe mental retardation. 61 57
12558115 2002
7
Filippi syndrome: report of three additional cases. 57 61
10533026 1999
8
Filippi syndrome: a new case with skeletal abnormalities. 61 57
7473664 1995
9
Craniodigital syndromes: report of a child with Filippi syndrome and discussion of differential diagnosis. 57 61
7717418 1995
10
Craniodigital syndrome of Scott: clinical and neuroradiological features of a new case. 57
17715284 2007
11
Postnatal short stature, microcephaly, severe syndactyly of hands and feet, dysmorphic face, and mental retardation: a new syndrome? 57
1316441 1992
12
The craniodigital syndrome of Scott: report of a second family. 57
2174209 1990
13
Unusual facial appearance, microcephaly, growth and mental retardation, and syndactyly. A new syndrome? 57
4073130 1985
14
A new craniodigital syndrome with mental retardation. 57
4323269 1971
15
Expanding the phenotype of Filippi Syndrome: a patient with early onset puberty. 61
30921095 2019
16
CKAP2L mutation confirms the diagnosis of Filippi syndrome. 61
29473684 2018
17
Mosaic CREBBP mutation causes overlapping clinical features of Rubinstein-Taybi and Filippi syndromes. 61
26956253 2016
18
Filippi Syndrome: Report of a Rare Case. 61
26813917 2015
19
A 2q24.3q31.1 microdeletion found in a patient with Filippi-like syndrome phenotype: a case report. 61
24924433 2014
20
Intellectual disability, unusual facial morphology and hand anomalies in sibs. 61
23949889 2013
21
A case of Filippi syndrome with atypical limb defects in a 3-year-old boy and a review of the literature. 61
23863342 2013
22
Multiple dental and skeletal abnormalities in an individual with filippi syndrome. 61
24222867 2013
23
How many entities exist for the spectrum of disorders associated with brachydactyly, syndactyly, short stature, microcephaly, and intellectual disability? 61
21416592 2011
24
Expanding the phenotype of Filippi syndrome: a report of three cases. 61
10532170 1999
25
An additional case of craniodigital syndrome: variable expression of the Filippi syndrome? 61
9377808 1997
26
Short stature, microcephaly, characteristic face, syndactyly and mental retardation: the Filippi syndrome. Report on a second family. 61
8395190 1993

Variations for Filippi Syndrome

ClinVar genetic disease variations for Filippi Syndrome:

6 (show all 11)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CKAP2L NM_001304361.2(CKAP2L):c.-280-59_-11del Deletion Pathogenic 162388 rs1553442237 GRCh37: 2:113514463-113514791
GRCh38: 2:112756886-112757214
2 CKAP2L NM_152515.5(CKAP2L):c.751del (p.Ser251fs) Deletion Pathogenic 162387 rs727502804 GRCh37: 2:113514197-113514197
GRCh38: 2:112756620-112756620
3 CKAP2L NM_152515.5(CKAP2L):c.554_555del (p.Lys185fs) Deletion Pathogenic 162389 rs727502805 GRCh37: 2:113514393-113514394
GRCh38: 2:112756816-112756817
4 CKAP2L NM_152515.5(CKAP2L):c.2T>C (p.Met1Thr) SNV Pathogenic 162385 rs548949031 GRCh37: 2:113522174-113522174
GRCh38: 2:112764597-112764597
5 CKAP2L NM_152515.5(CKAP2L):c.571dup (p.Ile191fs) Duplication Pathogenic 162384 rs727502802 GRCh37: 2:113514376-113514377
GRCh38: 2:112756799-112756800
6 CKAP2L NM_152515.5(CKAP2L):c.78_79insTT (p.Gly27fs) Insertion Pathogenic 162386 rs727502803 GRCh37: 2:113520105-113520106
GRCh38: 2:112762528-112762529
7 NT5DC4 , CKAP2L NM_152515.5(CKAP2L):c.1822+1G>A SNV Pathogenic 984719 GRCh37: 2:113500282-113500282
GRCh38: 2:112742705-112742705
8 CKAP2L NM_152515.5(CKAP2L):c.548_551CAAA[1] (p.Asn184fs) Microsatellite Likely pathogenic 804387 rs778989224 GRCh37: 2:113514393-113514396
GRCh38: 2:112756816-112756819
9 CKAP2L NM_152515.5(CKAP2L):c.1385A>T (p.Glu462Val) SNV Uncertain significance 1030263 GRCh37: 2:113513563-113513563
GRCh38: 2:112755986-112755986
10 CKAP2L NM_152515.5(CKAP2L):c.162T>G (p.Ile54Met) SNV Uncertain significance 775178 rs201346406 GRCh37: 2:113514786-113514786
GRCh38: 2:112757209-112757209
11 CKAP2L NM_152515.5(CKAP2L):c.199C>A (p.Pro67Thr) SNV Uncertain significance 1034319 GRCh37: 2:113514749-113514749
GRCh38: 2:112757172-112757172

Expression for Filippi Syndrome

Search GEO for disease gene expression data for Filippi Syndrome.

Pathways for Filippi Syndrome

GO Terms for Filippi Syndrome

Sources for Filippi Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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