Acrocapitofemoral Dysplasia (ACFD)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Acrocapitofemoral Dysplasia

MalaCards integrated aliases for Acrocapitofemoral Dysplasia:

Name: Acrocapitofemoral Dysplasia 58 12 54 60 76 38 30 13 6 45 15 41 74
Acfd 58 54 76
Bone Diseases, Developmental 45


Orphanet epidemiological data:

acrocapitofemoral dysplasia
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;


autosomal recessive

allelic to brachydactyly, type a1
cone-shaped epiphyses appear in early childhood and disappear with premature fusion of growth plate before puberty


acrocapitofemoral dysplasia:
Inheritance autosomal recessive inheritance


Summaries for Acrocapitofemoral Dysplasia

NIH Rare Diseases : 54 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 63446Disease definitionAcrocapitofemoral dysplasia is a recently delineated skeletal dysplasia, characterized clinically by short stature of variable degrees with short limbs, brachydactyly and narrow thorax.EpidemiologyIt has been described in 5 individuals in 2 families.Clinical descriptionAffected patients have normal intelligence. Radiographically, cone-shaped epiphyses are observed in the hands, the proximal part of the femur, and, to a variable degree, at the shoulders, knees, and ankles.EtiologyHomozygousmutations in the Indian hedgehog homolog gene (IHH; 2q33-q35), outside the region where brachydactyly type A-1 mutations are clustered, have been identified in affected patients.Genetic counselingThe condition is transmitted as an autosomal recessivetrait.Visit the Orphanet disease page for more resources.

MalaCards based summary : Acrocapitofemoral Dysplasia, also known as acfd, is related to cholera and autosomal recessive disease. An important gene associated with Acrocapitofemoral Dysplasia is IHH (Indian Hedgehog Signaling Molecule), and among its related pathways/superpathways is Hedgehog signaling pathway. The drugs Benzocaine and tannic acid have been mentioned in the context of this disorder. Affiliated tissues include bone, testes and skin, and related phenotypes are skeletal dysplasia and delayed skeletal maturation

Disease Ontology : 12 An osteochondrodysplasia characterized by skeletal dysplasia, bradydactyly and narrow thorax and has material basis in mutations in the Indian hedgehog homolog gene.

UniProtKB/Swiss-Prot : 76 Acrocapitofemoral dysplasia: An autosomal recessive disorder characterized by short stature of variable severity with postnatal onset. The most constant radiographic abnormalities are observed in the tubular bones of the hands and in the proximal part of the femur. Cone-shaped epiphyses or a similar epiphyseal configuration with premature epimetaphyseal fusion result in shortening of the skeletal components involved. Cone-shaped epiphyses are also present to a variable extent at the shoulders, knees and ankles.

Description from OMIM: 607778

Related Diseases for Acrocapitofemoral Dysplasia

Diseases related to Acrocapitofemoral Dysplasia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cholera 10.4
2 autosomal recessive disease 10.2
3 bone disease 9.7

Symptoms & Phenotypes for Acrocapitofemoral Dysplasia

Human phenotypes related to Acrocapitofemoral Dysplasia:

60 33 (show all 46)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 skeletal dysplasia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002652
2 delayed skeletal maturation 60 33 hallmark (90%) Very frequent (99-80%) HP:0002750
3 short stature 60 33 hallmark (90%) Very frequent (99-80%) HP:0004322
4 micromelia 60 33 hallmark (90%) Very frequent (99-80%) HP:0002983
5 short palm 60 33 hallmark (90%) Very frequent (99-80%) HP:0004279
6 coxa vara 60 33 hallmark (90%) Very frequent (99-80%) HP:0002812
7 hyperlordosis 60 33 frequent (33%) Frequent (79-30%) HP:0003307
8 ovoid vertebral bodies 60 33 frequent (33%) Frequent (79-30%) HP:0003300
9 small nail 60 33 frequent (33%) Frequent (79-30%) HP:0001792
10 genu varum 60 33 frequent (33%) Frequent (79-30%) HP:0002970
11 broad nail 60 33 frequent (33%) Frequent (79-30%) HP:0001821
12 flared iliac wings 60 33 frequent (33%) Frequent (79-30%) HP:0002869
13 cone-shaped metacarpal epiphyses 60 33 frequent (33%) Frequent (79-30%) HP:0006059
14 macrocephaly 60 33 occasional (7.5%) Occasional (29-5%) HP:0000256
15 pectus excavatum 60 33 occasional (7.5%) Occasional (29-5%) HP:0000767
16 scoliosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002650
17 pectus carinatum 60 33 occasional (7.5%) Occasional (29-5%) HP:0000768
18 narrow chest 60 33 occasional (7.5%) Occasional (29-5%) HP:0000774
19 short thorax 60 33 occasional (7.5%) Occasional (29-5%) HP:0010306
20 cone-shaped epiphysis 60 Very frequent (99-80%)
21 enlargement of the distal femoral epiphysis 33 HP:0006438
22 hypoplastic iliac wing 33 HP:0002866
23 brachydactyly 33 HP:0001156
24 disproportionate short-limb short stature 33 HP:0008873
25 short distal phalanx of finger 33 HP:0009882
26 hypoplasia of the ulna 33 HP:0003022
27 short metacarpal 33 HP:0010049
28 hypoplasia of the radius 33 HP:0002984
29 cupped ribs 33 HP:0000887
30 disproportionate short stature 33 HP:0003498
31 relative macrocephaly 33 HP:0004482
32 lumbar hyperlordosis 33 HP:0002938
33 short tibia 33 HP:0005736
34 short humerus 33 HP:0005792
35 abnormality of the femoral neck 60 Very frequent (99-80%)
36 short femur 33 HP:0003097
37 short ribs 33 HP:0000773
38 short femoral neck 33 HP:0100864
39 delayed ossification of carpal bones 33 HP:0001216
40 fibular overgrowth 33 HP:0003099
41 short proximal phalanx of thumb 33 HP:0009638
42 short proximal phalanx of finger 33 HP:0010241
43 cone-shaped capital femoral epiphysis 33 HP:0008789
44 cone-shaped epiphysis of the 1st metacarpal 33 HP:0010017
45 dysplasia of the femoral head 33 HP:0010575
46 small finger 33 HP:0030033

Symptoms via clinical synopsis from OMIM:

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum
pectus carinatum
rib cupping

Skeletal Hands:
short hands
delayed carpal bone age
cone-shaped epiphyses (metacarpals, thumbs, middle and distal phalanges)
short middle and distal phalanges

Skeletal Pelvis:
coxa vara
short femoral neck
cone-shaped epiphyses (proximal femur)
egg-shaped femoral head
short, flared iliac wings

Neurologic Central Nervous System:
normal intelligence

Skin Nails Hair Nails:
broad fingernails
small finger nails

Skeletal Feet:
cone-shaped epiphyses (ankles)

Skeletal Spine:
ovoid vertebral bodies
lumbar hyperlordosis
anterior notching of vertebral bodies

Skeletal Limbs:
genu varum
short limbs
cone-shaped epiphyses (proximal and distal tibia)
varus deformity (humeral head)
large distal femoral epiphyses

Growth Height:
normal birth length
short-limbed dwarfism
short stature, disproportionate

Chest External Features:
narrow thorax

Head And Neck Head:
relatively large head

Clinical features from OMIM:


Drugs & Therapeutics for Acrocapitofemoral Dysplasia

Drugs for Acrocapitofemoral Dysplasia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 379)
# Name Status Phase Clinical Trials Cas Number PubChem Id
Benzocaine Approved, Investigational Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable 1994-09-7, 94-09-7 2337
tannic acid Approved Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable 1401-55-4
Desflurane Approved Phase 4,Not Applicable 57041-67-5 42113
Sevoflurane Approved, Vet_approved Phase 4 28523-86-6 5206
Zoledronic Acid Approved Phase 4,Phase 3,Phase 2 118072-93-8 68740
Tranexamic Acid Approved Phase 4,Phase 3,Not Applicable 1197-18-8 5526
Atenolol Approved Phase 4,Phase 3,Phase 2 29122-68-7 2249
Ethinyl Estradiol Approved Phase 4 57-63-6 5991
Estradiol Approved, Investigational, Vet_approved Phase 4 50-28-2 5757
Desogestrel Approved Phase 4 54024-22-5 40973
Etonogestrel Approved, Investigational Phase 4 54048-10-1 6917715 40976
Polyestradiol phosphate Approved Phase 4 28014-46-2
Fentanyl Approved, Illicit, Investigational, Vet_approved Phase 4,Not Applicable 437-38-7 3345
Anastrozole Approved, Investigational Phase 4,Phase 3,Phase 2 120511-73-1 2187
Letrozole Approved, Investigational Phase 4,Phase 3,Phase 1 112809-51-5 3902
Hydromorphone Approved, Illicit Phase 4,Not Applicable 466-99-9 5284570
Morphine Approved, Investigational Phase 4 57-27-2 5288826
Ropivacaine Approved Phase 4,Not Applicable 84057-95-4 175805 71273
Ketorolac Approved Phase 4 74103-06-3, 66635-83-4 3826
Mecasermin Approved, Investigational Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable 68562-41-4
Teriparatide Approved, Investigational Phase 4,Phase 2 52232-67-4 16133850
Parathyroid hormone Approved, Investigational Phase 4,Phase 1,Phase 2 9002-64-6
Tesamorelin Approved, Investigational Phase 4,Phase 2 218949-48-5
Alendronate Approved Phase 4,Phase 2 66376-36-1, 121268-17-5 2088
Verapamil Approved Phase 4 52-53-9 2520
Perindopril Approved Phase 4,Phase 3 107133-36-8, 82834-16-0 107807
Ethanol Approved Phase 4 64-17-5 702
Acetylcholine Approved, Investigational Phase 4 51-84-3 187
Dopamine Approved Phase 4 62-31-7, 51-61-6 681
Risperidone Approved, Investigational Phase 4 106266-06-2 5073
Methylphenidate Approved, Investigational Phase 4 113-45-1 4158
Pamidronate Approved Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable 40391-99-9 4674
Methyclothiazide Approved Phase 4 135-07-9 4121
Calcium Approved, Nutraceutical Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable 7440-70-2 271
Vitamin D3 Approved, Nutraceutical Phase 4,Phase 1,Not Applicable 67-97-0 5280795 6221
Vitamin D Approved, Nutraceutical, Vet_approved Phase 4,Phase 2,Phase 1,Not Applicable 1406-16-2
Ergocalciferol Approved, Nutraceutical Phase 4,Phase 1,Not Applicable 50-14-6 5280793
38 Deslorelin Investigational, Vet_approved Phase 4,Phase 2 57773-65-6
39 Anesthetics Phase 4,Phase 1,Phase 2,Not Applicable
40 Anesthetics, Inhalation Phase 4,Not Applicable
41 Central Nervous System Depressants Phase 4,Phase 2,Phase 1,Not Applicable
42 Anesthetics, General Phase 4,Not Applicable
43 Platelet Aggregation Inhibitors Phase 4,Phase 2
44 Hormones Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable,Early Phase 1
45 Hormone Antagonists Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1
46 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable,Early Phase 1
47 Vaccines Phase 4
48 Imatinib Mesylate Phase 4 220127-57-1 123596
49 Calcium, Dietary Phase 4,Phase 2,Phase 3,Phase 1,Not Applicable
50 Analgesics Phase 4,Phase 3,Phase 2,Phase 1,Not Applicable

Interventional clinical trials:

(show top 50) (show all 655)
# Name Status NCT ID Phase Drugs
1 Pulmonary Mechanics During Minimally Invasive Repair of Pectus Excavatum Unknown status NCT01486953 Phase 4 Desflurane;Sevoflurane
2 Phase IV Clinical Study of Pegylated Somatropin (PEG Somatropin) to Treat Growth Hormone Deficiency Children Unknown status NCT02314676 Phase 4
3 Pegylated Somatropin (PEG Somatropin) in the Treatment of Children With Growth Hormone Deficiency Unknown status NCT02976675 Phase 4
4 Clinical Study of Pegylated Somatropin to Treat Children Growth Hormone Deficiency Unknown status NCT02908958 Phase 4
5 Immunodeficiency in Cartilage-hair Hypoplasia: Sub-project on Safety of Vaccination Against Chickenpox Unknown status NCT02383797 Phase 4
6 Assessment Of Gh-Igf-1 Axis In Children With Chronic Myelogenous Leukemia (CML) In Remission Unknown status NCT01901666 Phase 4 Growth Hormone
7 Assessing the Impact of Contraceptives on Bone Health Using 41Ca Active, not recruiting NCT02367846 Phase 4 Combined Oral Contraceptive (COC);Contraceptive Vaginal Ring (CVR)
8 Cryoanalgesia vs. Epidural in the Nuss Procedure Completed NCT02721017 Phase 4 Thoracic epidural (ropivicaine, fentanyl)
9 Aromatase Inhibitor Growth Study: Letrozole vs. Anastrozole Recruiting NCT02137538 Phase 4 Letrozole;Anastrozole
10 A Comparison Trial Between PCA and Epidural Analgesia for Pectus Excavatum Repair Terminated NCT02056301 Phase 4 Hydromorphone;Morphine
11 Comparison of IV PCA and Wound Infusion After Repair of Pectus Excavatum Completed NCT01908491 Phase 4
12 Long Term Study of Genotropin (Somatropin) for Short Children Born Small for Gestational Age (SGA) Completed NCT01859949 Phase 4 Genotropin (somatropin)
13 Predictive Value of the Insulin-like Growth Factor-1 (IGF-1) Generation Test for the Growth Response to Growth Hormone Treatment (PRED-IGF) Withdrawn NCT01438801 Phase 4 Nutropin [Somatropin (rDNA origin) for injection]
14 Short Stature Related Distress Completed NCT01246219 Phase 4 GH treatment (Genotropin);1 year treatment with placebo followed by optional 3 years of GH treatment
15 A 4 Year Combination Therapy of Growth Hormone and (GnRH) Agonist in Children With a Short Predicted Height Active, not recruiting NCT00840944 Phase 4 somatropin;triptorelin
16 Biochemical Markers of Growth Response to Growth Hormone Treatment in Children With Idiopathic Short Stature Completed NCT00458263 Phase 4 Somatotropin growth hormone recombinant human
17 Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid Recruiting NCT03735537 Phase 4 Teriparatide Pen Injector;Zoledronic Acid
18 Extension Study of Pegylated Somatropin to Treat Growth Retardation Caused by Endogenous Growth Hormone Deficiency in Children Recruiting NCT03290235 Phase 4 PEG-somatropin
19 Pegylated Somatropin (PEG Somatropin) in the Treatment of Children With Growth Hormone Deficiency Recruiting NCT03249480 Phase 4
20 Body Composition and Adipose Tissue in HIV Recruiting NCT03226821 Phase 4 Tesamorelin
21 Phase IV Clinical Study of Pegylated Somatropin (PEG Somatropin) to Treat Growth Hormone Deficiency Children (Clinical Trial I) Recruiting NCT02380235 Phase 4
22 A Multicentre, Randomised, Open-label, Controlled Study to Evaluate the Effects of Saizen® on Cardiac Function in Growth Hormone Deficient(GHD) Subjects During the Transition Phase From Childhood to Adulthood Completed NCT01157793 Phase 4 r-hGH;r-hGH
23 A Post-Marketing Study of the Immunogenicity of Somatropin (Ribosomal Deoxyribo Nucleic Acid [rDNA] Origin) Injection (Nutropin AQ®) in Children With Growth Hormone Deficiency Completed NCT02311894 Phase 4 Somatropin
24 Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta Completed NCT02303873 Phase 4 Alendronate
25 An Open-label Phase 4 Study to Explore Immunogenicity of the Liquid Formulation of Saizen® in Subjects With Adult Growth Hormone Deficiency (AGHD) Completed NCT01806298 Phase 4 Saizen® solution for injection (referred as Saizen®)
26 Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta Completed NCT01713231 Phase 4
27 Cardiovascular Effects on Growth Hormone Therapy in Adults With Growth Hormone Deficiency Terminated NCT01698944 Phase 4 somatropin
28 Evaluation of the Ease of Use, Preference, and Safety of EutropinPen Inj. Completed NCT03015909 Phase 4 Somatropin
29 Safety and Efficacy of SR-hGH (Sustained-release Human Growth Hormone, Declage Inj.) Completed NCT01605331 Phase 4 sustained-release recombinant human GH (SR-rhGH)
30 Effect of Somatropin on Left Ventricular Mass in Growth Hormone Deficient Adult Patients Completed NCT01562834 Phase 4 somatropin;placebo
31 Growth Hormone and Endothelial Function in Children Completed NCT00373386 Phase 4 growth hormone
32 The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery Completed NCT02188576 Phase 4 high dose TXA;Low dose TXA
33 Comparison of a Needle-free Injection Method With a Needle-syringe Injection Method Completed NCT00990340 Phase 4
34 Growth Hormone and Glucose Metabolism Completed NCT00929799 Phase 4 recombinant human Growth Hormone (Genotropin® )
35 Easypod United States User Trial Completed NCT00689260 Phase 4
36 Liquid Somatropin Formulation in Children With Growth Hormone Deficiency Completed NCT00567385 Phase 4 somatropin
37 Comparison of Two Growth Hormone Dosing Methods in Adults With Growth Hormone Deficiency Completed NCT00490191 Phase 4 Somatropin
38 Comparison of Medical Therapies in Marfan Syndrome. Completed NCT01295047 Phase 4 Atenolol;VERAPAMIL;Perindopril
39 IGF1 Generation Test Completed NCT00145457 Phase 4
40 Endocrine Dysfunction and Growth Hormone Deficiency in Children With Optic Nerve Hypoplasia Completed NCT00140413 Phase 4 Nutropin AQ
41 Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta Completed NCT00131469 Phase 4 Teriparatide (FORTEO);Placebos
42 Comparison of a Bone Product to Bone Dust in Ossification of Small Calvarial Defects. Withdrawn NCT01006148 Phase 4
43 Tranexamic Acid for Craniofacial Surgery Terminated NCT00722436 Phase 4 Tranexamic acid;saline
44 First Year Growth Response Associated Genetic Markers Validation Phase IV Open-label Study in Growth Hormone Deficient and Turner Syndrome Pre-pubertal Children: the PREDICT Pharmacogenetics Validation Study Completed NCT01419249 Phase 4
45 Is There a Sensibility Increased in the Growth Hormone at Child With Prader-Willi Syndrome? Completed NCT01298180 Phase 4 Growth hormone (Genotonorm® or Omnitrope®)
46 Norditropin NordiFlex® Device Compared to the Device Previously Used by Patients or Parents Completed NCT01245374 Phase 4
47 Sub-Paraspinal Block in Nuss Patients. A Pilot Project Completed NCT02169297 Phase 4
48 A Study to Optimize Growth Hormone Dosing in Children With Chronic Kidney Disease by Measuring IGF-1 Levels in Blood Completed NCT00212758 Phase 4 Nutropin AQ
49 GH and Cardiovascular Risk Factors Completed NCT01877512 Phase 4 Change in daily dosage of Growth Hormone
50 Predictive Markers in Chinese Growth Hormone Deficiency (GHD) Children Treated With Saizen® Completed NCT01187550 Phase 4 Recombinant human growth hormone (r-hGH)

Search NIH Clinical Center for Acrocapitofemoral Dysplasia

Cochrane evidence based reviews: bone diseases, developmental

Genetic Tests for Acrocapitofemoral Dysplasia

Genetic tests related to Acrocapitofemoral Dysplasia:

# Genetic test Affiliating Genes
1 Acrocapitofemoral Dysplasia 30 IHH

Anatomical Context for Acrocapitofemoral Dysplasia

MalaCards organs/tissues related to Acrocapitofemoral Dysplasia:

Bone, Testes, Skin, Brain, Pituitary, Thymus, Heart

Publications for Acrocapitofemoral Dysplasia

Articles related to Acrocapitofemoral Dysplasia:

# Title Authors Year
Activation of both acfA and acfD transcription by Vibrio cholerae ToxT requires binding to two centrally located DNA sites in an inverted repeat conformation. ( 15853890 )
Acrocapitofemoral dysplasia: an autosomal recessive skeletal dysplasia with cone shaped epiphyses in the hands and hips. ( 12624140 )
Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips. ( 12632327 )
Sequence analysis of the Vibrio cholerae acfD gene reveals the presence of an overlapping reading frame, orfZ, which encodes a protein that shares sequence similarity to the FliA and FliC products of Salmonella. ( 8063108 )
Structural analysis of the acfA and acfD genes of Vibrio cholerae: effects of DNA topology and transcriptional activators on expression. ( 1644747 )
No ostriches in sight. Just an octopus. An ACFD/AFDC position paper pursuant to the manpower and prelicensure conferences. ( 3545398 )
ACFD supports concept of consumer involvement in accreditation process. ( 1058199 )

Variations for Acrocapitofemoral Dysplasia

UniProtKB/Swiss-Prot genetic disease variations for Acrocapitofemoral Dysplasia:

# Symbol AA change Variation ID SNP ID
1 IHH p.Pro46Leu VAR_015981 rs121917856
2 IHH p.Val190Ala VAR_015986 rs121917857

ClinVar genetic disease variations for Acrocapitofemoral Dysplasia:

# Gene Variation Type Significance SNP ID Assembly Location
1 IHH NM_002181.3(IHH): c.137C> T (p.Pro46Leu) single nucleotide variant Pathogenic rs121917856 GRCh37 Chromosome 2, 219925053: 219925053
2 IHH NM_002181.3(IHH): c.137C> T (p.Pro46Leu) single nucleotide variant Pathogenic rs121917856 GRCh38 Chromosome 2, 219060331: 219060331
3 IHH NM_002181.3(IHH): c.569T> C (p.Val190Ala) single nucleotide variant Pathogenic rs121917857 GRCh37 Chromosome 2, 219922163: 219922163
4 IHH NM_002181.3(IHH): c.569T> C (p.Val190Ala) single nucleotide variant Pathogenic rs121917857 GRCh38 Chromosome 2, 219057441: 219057441

Expression for Acrocapitofemoral Dysplasia

Search GEO for disease gene expression data for Acrocapitofemoral Dysplasia.

Pathways for Acrocapitofemoral Dysplasia

Pathways related to Acrocapitofemoral Dysplasia according to KEGG:

# Name Kegg Source Accession
1 Hedgehog signaling pathway hsa04340

GO Terms for Acrocapitofemoral Dysplasia

Sources for Acrocapitofemoral Dysplasia

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
33 HPO
34 ICD10
35 ICD10 via Orphanet
39 LifeMap
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
56 Novoseek
59 OMIM via Orphanet
63 PubMed
71 SNOMED-CT via Orphanet
73 Tocris
75 UMLS via Orphanet
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