BRACHYDACTYLY

Brachydactyly, or shortening of the digits, is a hereditary disorder characterized by abnormal development of the metacarpals, phalanges, or both. It is usually transmitted as an autosomal dominant gene with variable expression.  The digital shortening of brachydactyly is secondary to some early growth disturbance that causes anomalies in or the absence of bony segments of the digits, but it can also be part of another syndrome.¹ In most cases, not all segments are involved simultaneously, but minor anomalies of other bones are also frequently present. ² Aside from the physical characteristics of brachydactyly, other symptoms are typically not present unless they are related to an associated syndrome. For this reason, treatment is not necessary in the majority of brachydactyly cases, especially if no other syndrome is present. In rare cases, physical therapy may be used to improve hand function, while plastic surgery is reserved for improving appearance and function in severe cases.³

Pathophysiology

• As in all congenital anomalies, brachydactyly can occur either as an isolated malformation or as a part of a complex malformation syndrome
  • The number of syndromes associated with brachydactyly is extensive and includes Down’s syndrome and Cushing’s syndrome
  • Brachydactyly may also occur along with other hand malformations, such as syndactyly, polydactyly, reduction defects, or symphalangism³
  • Brachydactyly typically follows an autosomal dominant pattern of inheritance with variable expression and penetrance, but autosomal recessive cases have also been documented; the developmental anomaly is mainly confined to the bones of the hands and feet, although there may be more widespread manifestations of the disorder to the bony skeleton with subtle changes elsewhere in the body^1,3
  • Molecular analysis of isolated forms of brachydactyly has shed some light on the role of certain genes in normal human skeletogenesis and limb formation, which include BMPR1B, HOXD13, ROR2, and CDMP1³

Related Anatomy

• The orinal seven types described by Bell ⁷ in 1951 has been expanded to 11 types of isolated brachydactyly.  These eleven typyes of brachydacyly have been identified with minimal degrees of phenotypic overlap³:
• Type A1: The shortening is confined to the middle phalanx of the fingers and the proximal phalanx of the thumbs
• Type A2: The shortening is confined to the middle phalanx of the index finger and possibly the little finger
• Type A3: The shortening is confined to the middle phalanx of the little finger This type is associated with clinodactyly and lateral angulation of the little finger. This type may occur as part of certain syndromes, particularly mongolism, in which the anomaly is present in 50% of cases
• Type A4: Unusual type of brachydactyly in which brachymesophalangy mainly affects the index and little fingers
• Type A5: Involves the absence of the middle phalanges and nail dysplasia with duplicated terminal phalanx of the thumb
  • Shares similarities with Type B brachydactyly
• Type A6: Brachymesophalangy with mesomelic short limbs and carpal osseous abnormalities
• Type A7: Also known as brachydactyly smorgasbord type
• Type B: The middle phalanx of the fingers is anomalous and the terminal phalanges are often absent, reducing the fingers to short stumps with only a single interphalangeal joint and no finger nails; the thumbs are usually normal but may be flattened and/or split
• Type C: The anomalies in this type are more complex and differ from one finger to another, but it is usually characterized by brachymesophalangy of the index, middle and little fingers, with hyperphalangy of the index and middle finger and shortening of the first metacarpal
  • The fourth finger is usually the longest digit
  • Short metacarpals and symphalangism may also occur
• Type D: The terminal phalanx of the thumbs is short and broad with corresponding hypoplastic nails
• Type E: There is shortening of the metacarpals with wide variability in the number of digits involved
  • The fourth finger is most frequently affected^1,3
  • Brachydactyly can also be classified into the following three groups:
    1. Brachydactyly by simple shortening of the digits, with the number of bones remaining normal
    2. Brachydactyly by ankylosis of the bones of the digit
    3. Brachydactyly by partial loss of bone, either in the metacarpus or phalanges⁴

Exam Findings, Signs and Positive Tests

• A clinical evaluation of both the hands and feet and a family history that takes nonpenetrance into account is extremely important for diagnosing brachydactyly; if possible, a clinical evaluation of at least the first-degree relatives should be performed³
• A prenatal diagnosis is usually not indicated for isolated forms of brachydactyly, but it may be appropriate in syndromic forms
  • Short phalanges may not be clearly evident by fetal ultrasonography early in development, and will only be visible later on, if they are expressed
  • Molecular studies of chorionic villus sampling at 11 weeks of gestation and by amniocentesis after the 14th week of gestation can provide antenatal diagnosis if the causative mutation in the family is known³
• Genetic counseling may also be used and depends on both the pattern of inheritance of the type of brachydactyly present in the family and the presence or absence of accompanying symptoms
  • If the brachydactyly follows an autosomal dominant pattern of inheritance, the chance of recurrence in offspring of affected individuals is 50%
  • If the brachydactyly follows an autosomal recessive pattern of inheritance, the risk of recurrence is 25%³

Work-Up Options

• Radiologic evaluation may be helpful to determine which bones are affected and to diagnose the type of brachydactyly present
  • An X-ray of the hands with a posteroanterior view will show the selective distribution of the hypoplasia and/or aplasia of the middle phalanges³
• If symptoms in other parts of the body are also present, specific studies may be needed depending on the accompanying symptoms
  • A full skeletal X-ray may be performed to determine if the brachydactyly is part of another syndrome
  • Molecular analysis in isolated forms or syndromic cases of brachydactyly should be carried out if results could have consequences for patient care and/or for genetic counseling³

Incidence and Related Conditions

• Most types of isolated brachydactyly are rare, except types A3 and D
  • Type A3 is very common, with a reported prevalence ranging from 3.4-21%
  • Type D is also common, with a prevalence ranging from 0.41-4%
  • Both types A3 and D have a particularly high prevalence in the Japanese population⁵
  • Syndactyly, polydactyly, and/or clinodactyly
  • Reduction defects
  • Symphalangism
  • Lateral angulation of digits
  • Pseudarthrosis
  • Brachymetatarsus IV
  • Sugarman brachydactyly
  • Kirner’s deformity
  • Robinow syndrome
  • Rubinstein-Taybi syndrome
  • Albright hereditary osteodystrophy
  • Brachydactyly type E with hypertension
  • du Pan syndrome

Differential Diagnosis

• Clinodactyly
• Pseudohypoparathyroidism
  • Acrodysostosis
  • Kirner’s deformity
• Camptodactyly

Surgical Complications:

• Infection
• Incomplete correction of the deformity
• Excessive shortening of the digit

• The overall prognosis for affected individuals depends strongly on the nature of the brachydactyly, and may vary from excellent to severely impaired hand function
• If the brachydactyly is part of another syndrome, the prognosis usually depends on the nature of the associated issues present³

• Brachydactyly was the first human condition found to obey the Mendelian manner of inheritance as a dominant characteristic
• Brachydactyly is one of the ten categories of hand malformations classified by Temtamy & McKusick in their original work on the genetics of hand malformations⁵
• The shortening of fingers in brachydactyly is much more rare than other malformations such as polydactyly and ectrodactyly
• The hands are more commonly affected than the feet in most cases of brachydactyly⁴
• Associated conditions include : Hypoplasia of the metacarpals and/or phalanges; aplasia of the metacarpals and/or phalanges; nail dysplasia; broad thumb; synostosis and symphalangism.
• Brachydactyly rarely results in a functiional loss.  Therefore, surgical treatment rarely is required. ⁶
• Brachydactyly Type C is not associated with visceral abnormalities.⁶
• Surgicaal treatment of brachydactyly can worsen the clinical situatiion by causing additiional shortening.

Cited

1. Chen VT. Brachydactyly. Hand 1978;10(2):191-201. PMID: 711003
2. Hoefnagel D, Gerald PS. Hereditary brachydactyly. Ann Hum Genet 1966;29(4):377-82. PMID: 5961825
3. Temtamy SA, Aglan MS. Brachydactyly. Orphanet J Rare Dis 2008;3(15):1750-1172. PMID: 18554391
4. Marshall R. Note on a Family with Brachydactyly. Arch Dis Child 1929;4(24):385-8. PMID: 21031787
5. Temtamy SA, McKusick VA. The genetics of hand malformations. Birth Defects Orig Artic Ser 1978;14(3):i-xviii, 1-619. PMID: 215242
6. Burgess RC. Brachydactyly type C. J Hand Surg Am 2001;26(1):31-9. PMID: 11172365
7. Bell J. On brachydactyly and symphalangism. In Penrose LS, ed. Treasury of human inheritance.  Vol.5. London:  Cambridge University Press, 1951: 1-31.

Reviews

1. Thomas-Teinturier C, Pereda A, Garin I, et al. Report of two novel mutations in PTHLH associated with brachydactyly type E and literature review. Am J Med Genet 2016;170(3):734-42. PMID: 26640227
2. David A, Vincent M, Quere MP, et al. Isolated and syndromic brachydactylies: Diagnostic value of hand X-rays. Diagn Interv Imaging 2015;96(5):443-8. PMID: 25758756

Classics

1. Chen VT. Brachydactyly. Hand 1978;10(2):191-201. PMID: 711003
2. Temtamy SA, McKusick VA. The genetics of hand malformations. Birth Defects Orig Artic Ser 1978;14(3):i-xviii, 1-619. PMID: 215242
3. Bell J. On brachydactyly and symphalangism. In Penrose LS, ed. Treasury of human inheritance.  Vol.5. London:  Cambridge University Press, 1951: 1-31.