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Brachydactyly type A1(BDA1)

MedGen UID:: 354673
•Concept ID:: C1862151
•: Disease or Syndrome

Synonyms:	Brachydactyly Farabee type; SHORT STATURE WITH NONSPECIFIC SKELETAL ABNORMALITIES 2
SNOMED CT:	Brachydactyly type A1 (715720006); Brachydactyly Farabee type (715720006)
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Related genes: Gene(s) associated with related conditions. For conditions in a hierarchy, the parent condition will list the genes associated with the children conditions.	GDF5, IHH, BMPR1B

HPO:	HP:0009371
Monarch Initiative:	MONDO:0007215
OMIM®:	112500
Orphanet:	ORPHA93388

Definition

Brachydactyly type A1 (BDA1) is an autosomal dominant disorder characterized by shortening of the middle phalanges of the digits of the hand, with or without symphalangism. Mild short stature is often present. Considerable inter- and intrafamilial variability has been observed, with all or only some digits affected, and complete absence of the middle phalanx in some cases. Metacarpals may also be shortened, and clinodactyly, camptodactyly, and ulnar deviation have been reported. Some patients exhibit abnormalities of the feet (Zhu et al., 2007; Lodder et al., 2008; Byrnes et al., 2009; Vasques et al., 2018). Genetic Heterogeneity of Brachydactyly Type A1 BDA1B (607004) has been mapped to chromosome 5. BDA1C (615072) is caused by mutation in the GDF5 gene (601146) on chromosome 20q11. BDA1D (616849) is caused by mutation in the BMPR1B gene (603248) on chromosome 4q22. [from OMIM]

Clinical features

From HPO

Brachydactyly

MedGen UID:: 67454
•Concept ID:: C0221357
•: Congenital Abnormality

Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.

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Broad palm

MedGen UID:: 75535
•Concept ID:: C0264142
•: Congenital Abnormality

For children from birth to 4 years of age the palm width is more than 2 SD above the mean; for children from 4 to 16 years of age the palm width is above the 95th centile; or, the width of the palm appears disproportionately wide for the length.

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Short metacarpal

MedGen UID:: 323064
•Concept ID:: C1837084
•: Anatomical Abnormality

Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.

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Short distal phalanx of finger

MedGen UID:: 326590
•Concept ID:: C1839829
•: Finding

Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.

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Short palm

MedGen UID:: 334684
•Concept ID:: C1843108
•: Finding

Short palm.

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Radial deviation of the 2nd finger

MedGen UID:: 335012
•Concept ID:: C1844709
•: Finding

Displacement of the 2nd finger towards the radial side.

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Clinodactyly of the 5th finger

MedGen UID:: 340456
•Concept ID:: C1850049
•: Congenital Abnormality

Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).

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Short proximal phalanx of thumb

MedGen UID:: 340786
•Concept ID:: C1855091
•: Finding

Hypoplastic (short) proximal phalanx of the thumb. In contrast to the proximal phalanges of the digits 2-5, the proximal phalanx of the thumb is embryologically equivalent to the middle phalanges of the other digits, whereas the first metacarpal is embryologically of phalangeal origin and as such equivalent to the proximal phalanges of the other digits.

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Absent distal interphalangeal creases

MedGen UID:: 350011
•Concept ID:: C1861349
•: Finding

Absence of the distal interphalangeal flexion creases of the fingers.

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Aplasia/Hypoplasia of the middle phalanges of the hand

MedGen UID:: 354674
•Concept ID:: C1862152
•: Finding

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Proportionate shortening of all digits

MedGen UID:: 350606
•Concept ID:: C1862157
•: Congenital Abnormality

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Short proximal phalanx of hallux

MedGen UID:: 396305
•Concept ID:: C1862159
•: Finding

Underdevelopment (hypoplasia) of the proximal phalanx of big toe.

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Aplasia/Hypoplasia of the middle phalanges of the toes

MedGen UID:: 869548
•Concept ID:: C4023976
•: Finding

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Radial deviation of the 3rd finger

MedGen UID:: 869914
•Concept ID:: C4024345
•: Anatomical Abnormality

Displacement of the 3rd finger towards the radial side (i.e., towards the thumb).

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Radial deviation of the 4th finger

MedGen UID:: 870042
•Concept ID:: C4024473
•: Anatomical Abnormality

Displacement of the 4th finger towards the radial side (i.e., towards the thumb).

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Slender metacarpals

MedGen UID:: 870626
•Concept ID:: C4025077
•: Anatomical Abnormality

Decreased width of the metacarpal bones (that is, reduced diameter).

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Thin proximal phalanges with broad epiphyses of the hand

MedGen UID:: 892976
•Concept ID:: C4025079
•: Anatomical Abnormality

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Broad metacarpal epiphyses

MedGen UID:: 870636
•Concept ID:: C4025088
•: Anatomical Abnormality

Increased side-to-side width of the metacarpal epiphyses.

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Flattened metatarsal heads

MedGen UID:: 870783
•Concept ID:: C4025240
•: Anatomical Abnormality

Abnormally flat shape of the heads of the metatarsal bones.

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Short stature

MedGen UID:: 87607
•Concept ID:: C0349588
•: Finding

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

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Distal symphalangism of hands

MedGen UID:: 350607
•Concept ID:: C1862158
•: Finding

The term distal symphalangism refers to a bony fusion of the distal and middle phalanges of the digits of the hand, in other words the distal interphalangeal joint (DIJ) is missing which can be seen either on x-rays or as an absence of the distal interphalangeal finger creases.

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Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVBrachydactyly type A1

Dysostosis with brachydactyly without extraskeletal manifestations
- Brachydactyly type A1

Follow this link to review classifications for Brachydactyly type A1 in Orphanet.

Conditions with this feature

Eiken syndrome

MedGen UID:: 325097
•Concept ID:: C1838779
•: Congenital Abnormality

Eiken syndrome (EKNS) is an autosomal recessive skeletal dysplasia characterized by delayed ossification of bones, epiphyseal dysplasia, and bone remodeling abnormalities. Type A1 brachydactyly (see 112500), supernumerary epiphyses of proximal phalanges and metacarpals, and failure of eruption of primary teeth have also been described. Defining radiologic features include delayed ossification of epiphyses and primary ossification centers of short tubular bones, modeling abnormalities of tubular bones, and angel-shaped phalanges (Jacob et al., 2019). See 603740 for a disorder with similar radiologic features.

See: Condition Record

Thumb stiffness-brachydactyly-intellectual disability syndrome

MedGen UID:: 396073
•Concept ID:: C1861166
•: Disease or Syndrome

A rare, genetic, congenital limb malformation syndrome characterized by bilateral thumb ankylosis, type A brachydactyly and mild to moderate intellectual disability. Patients present thumb stiffness and abnormalities of the metacarpal bones, frequently associated with mild facial dysmorphism and signs of obesity. There have been no further descriptions in the literature since 1990.

See: Condition Record

Eiken syndrome

Thumb stiffness-brachydactyly-intellectual disability syndrome

Recent clinical studies

Etiology

Clinical and Molecular Description of 16 Families With Heterozygous IHH Variants.

Sentchordi-Montané L, Benito-Sanz S, Aza-Carmona M, Pereda A, Parrón-Pajares M, de la Torre C, Vasques GA, Funari MFA, Travessa AM, Dias P, Suarez-Ortega L, González-Buitrago J, Portillo-Najera NE, Llano-Rivas I, Martín-Frías M, Ramírez-Fernández J, Sánchez Del Pozo J, Garzón-Lorenzo L, Martos-Moreno GA, Alfaro-Iznaola C, Mulero-Collantes I, Ruiz-Ocaña P, Casano-Sancho P, Portela A, Ruiz-Pérez L, Del Pozo A, Vallespín E, Solís M, Lerario AM, González-Casado I, Ros-Pérez P, Pérez de Nanclares G, Jorge AAL, Heath KE
J Clin Endocrinol Metab 2020 Aug 1;105(8) doi: 10.1210/clinem/dgaa218. PMID: 32311039

p.E95K mutation in Indian hedgehog causing brachydactyly type A1 impairs IHH/Gli1 downstream transcriptional regulation.

Shen L, Ma G, Shi Y, Ruan Y, Yang X, Wu X, Xiong Y, Wan C, Yang C, Cai L, Xiong L, Gong X, He L, Qin S
BMC Genet 2019 Jan 16;20(1):10. doi: 10.1186/s12863-018-0697-5. PMID: 30651074 Free PMC Article

IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

Vasques GA, Funari MFA, Ferreira FM, Aza-Carmona M, Sentchordi-Montané L, Barraza-García J, Lerario AM, Yamamoto GL, Naslavsky MS, Duarte YAO, Bertola DR, Heath KE, Jorge AAL
J Clin Endocrinol Metab 2018 Feb 1;103(2):604-614. doi: 10.1210/jc.2017-02026. PMID: 29155992

Answering a century old riddle: brachydactyly type A1.

Gao B, He L
Cell Res 2004 Jun;14(3):179-87. doi: 10.1038/sj.cr.7290218. PMID: 15225411

Clinical and radiological assessment of a family with mild brachydactyly type A1: the usefulness of metacarpophalangeal profiles.

Armour CM, Bulman DE, Hunter AG
J Med Genet 2000 Apr;37(4):292-6. doi: 10.1136/jmg.37.4.292. PMID: 10745048 Free PMC Article

See all (5)

Diagnosis

Deletion of 2 amino acids in IHH in a Japanese family with brachydactyly type A1.

Ozaki N, Okuda H, Kobayashi H, Harada KH, Inoue S, Youssefian S, Koizumi A
BMC Med Genomics 2021 Jul 27;14(1):190. doi: 10.1186/s12920-021-01042-6. PMID: 34315464 Free PMC Article

Clinical and Molecular Description of 16 Families With Heterozygous IHH Variants.

Duplication of PTHLH causes osteochondroplasia with a combined brachydactyly type E/A1 phenotype with disturbed bone maturation and rhizomelia.

Flöttmann R, Sowinska-Seidler A, Lavie J, Chateil JF, Lacombe D, Mundlos S, Horn D, Spielmann M
Eur J Hum Genet 2016 Aug;24(8):1132-6. Epub 2016 Jan 6 doi: 10.1038/ejhg.2015.266. PMID: 26733284 Free PMC Article

Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1.

Racacho L, Byrnes AM, MacDonald H, Dranse HJ, Nikkel SM, Allanson J, Rosser E, Underhill TM, Bulman DE
Eur J Hum Genet 2015 Dec;23(12):1640-5. Epub 2015 Mar 11 doi: 10.1038/ejhg.2015.38. PMID: 25758993 Free PMC Article

Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels.

Ma G, Yu J, Xiao Y, Chan D, Gao B, Hu J, He Y, Guo S, Zhou J, Zhang L, Gao L, Zhang W, Kang Y, Cheah KS, Feng G, Guo X, Wang Y, Zhou CZ, He L
Cell Res 2011 Sep;21(9):1343-57. Epub 2011 May 3 doi: 10.1038/cr.2011.76. PMID: 21537345 Free PMC Article

See all (7)

Therapy

IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

Mutation screening in candidate genes in four Chinese brachydactyly families.

Dong S, Wang Y, Tao S, Zheng F
Ann Clin Lab Sci 2015 Winter;45(1):94-9. PMID: 25696018

See all (2)

Prognosis

IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1.

Mutations in GDF5 presenting as semidominant brachydactyly A1.

Byrnes AM, Racacho L, Nikkel SM, Xiao F, MacDonald H, Underhill TM, Bulman DE
Hum Mutat 2010 Oct;31(10):1155-62. doi: 10.1002/humu.21338. PMID: 20683927

See all (3)

Clinical prediction guides

Clinical and Molecular Description of 16 Families With Heterozygous IHH Variants.

IHH Gene Mutations Causing Short Stature With Nonspecific Skeletal Abnormalities and Response to Growth Hormone Therapy.

Two novel disease-causing variants in BMPR1B are associated with brachydactyly type A1.

A large duplication involving the IHH locus mimics acrocallosal syndrome.

Yuksel-Apak M, Bögershausen N, Pawlik B, Li Y, Apak S, Uyguner O, Milz E, Nürnberg G, Karaman B, Gülgören A, Grzeschik KH, Nürnberg P, Kayserili H, Wollnik B
Eur J Hum Genet 2012 Jun;20(6):639-44. Epub 2012 Jan 11 doi: 10.1038/ejhg.2011.250. PMID: 22234151 Free PMC Article

Mutations in GDF5 presenting as semidominant brachydactyly A1.

Byrnes AM, Racacho L, Nikkel SM, Xiao F, MacDonald H, Underhill TM, Bulman DE
Hum Mutat 2010 Oct;31(10):1155-62. doi: 10.1002/humu.21338. PMID: 20683927

See all (7)

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Brachydactyly type A1(BDA1)

Definition

Clinical features

Term Hierarchy

Conditions with this feature

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Molecular resources

Consumer resources

Reviews

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