Hand-foot-genital syndrome

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Hand-Foot-Genital Syndrome
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This condition is inherited in an autosomal dominant manner
Specialty Medical genetics   OOjs UI icon edit-ltr-progressive.svg

Hand-foot-genital syndrome (HFGS) is characterized by limb malformations and urogenital defects. Mild bilateral shortening of the thumbs and great toes, caused primarily by shortening of the distal phalanx and/or the first metacarpal or metatarsal, is the most common limb malformation and results in impaired dexterity or apposition of the thumbs. Urogenital abnormalities include abnormalities of the ureters and urethra and various degrees of incomplete Müllerian fusion in females and hypospadias of variable severity with or without chordee in males. Vesicoureteral reflux, recurrent urinary tract infections, and chronic pyelonephritis are common; fertility is normal. [1] [2]

Contents

Cause

Hand-foot-genital syndrome is inherited in an autosomal dominant manner. The proportion of cases caused by de novo mutations is unknown because of the small number of individuals described. If a parent of the proband is affected, the risk to the siblings is 50%. When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low. Each child of an individual with HFGS has a 50% chance of inheriting the mutation. Prenatal testing may be available through laboratories offering custom prenatal testing for families in which the disease-causing mutation has been identified in an affected family member. [1]

Diagnosis

Diagnosis is based on physical examination including radiographs of the hands and feet and imaging studies of the kidneys, bladder, and female reproductive tract. HOXA13 is the only gene known to be associated with HFGS. Approximately 60% of mutations are polyalanine expansions. Molecular genetic testing is clinically available.[ citation needed ]

Additional findings

Additional findings that may be present in HFGS according to the latest research are: [2]

Radiographic findings

Urogenital Defects

Females may have the following:

Males may have the following:

Treatment

Related Research Articles

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A finger is a limb of the human body and a type of digit, an organ of manipulation and sensation found in the hands of humans and other primates. Normally humans have five digits, the bones of which are termed phalanges, on each hand, although some people have more or fewer than five due to congenital disorders such as polydactyly or oligodactyly, or accidental or medical amputations. The first digit is the thumb, followed by index finger, middle finger, ring finger, and little finger or pinkie. According to different definitions, the thumb can be called a finger, or not.

Polydactyly Physical anomaly involving extra fingers or toes

Polydactyly or polydactylism, also known as hyperdactyly, is an anomaly in humans and animals resulting in supernumerary fingers and/or toes. Polydactyly is the opposite of oligodactyly.

Thumb First digit of the hand

The thumb is the first digit of the hand. When a person is standing in the medical anatomical position, the thumb is the outermost digit. The Medical Latin English noun for thumb is pollex, and the corresponding adjective for thumb is pollical.

Metacarpal bones

In human anatomy, the metacarpal bones or metacarpus, form the intermediate part of the skeletal hand located between the phalanges of the fingers and the carpal bones of the wrist which forms the connection to the forearm. The metacarpal bones are analogous to the metatarsal bones in the foot.

Upper limb

The upper limb or upper extremity is the region in a vertebrate animal extending from the deltoid region up to and including the hand, including the arm, axilla and shoulder.

Phalanx bone

The phalanges are digital bones in the hands and feet of most vertebrates. In primates, the thumbs and big toes have two phalanges while the other digits have three phalanges. The phalanges are classed as long bones.

The development of the urinary system begins during prenatal development, and relates to the development of the urogenital system – both the organs of the urinary system and the sex organs of the reproductive system. The development continues as a part of sexual differentiation.

Vaginal atresia is a condition in which the vagina is abnormally closed or absent. The main causes can either be complete vaginal hypoplasia, or a vaginal obstruction, often caused by an imperforate hymen or, less commonly, a transverse vaginal septum. It results in uterovaginal outflow tract obstruction. This condition does not usually occur by itself within an individual, but coupled with other developmental disorders within the female. The disorders that are usually coupled with a female who has vaginal atresia are Rokitansky-Mayer- Küster-Hauser syndrome, Bardet-Biedl syndrome, or Fraser syndrome. One out of every 5,000 women have this abnormality.

In human anatomy, the extensor pollicis longus muscle (EPL) is a skeletal muscle located dorsally on the forearm. It is much larger than the extensor pollicis brevis, the origin of which it partly covers and acts to stretch the thumb together with this muscle.

Flexor pollicis brevis muscle

The flexor pollicis brevis is a muscle in the hand that flexes the thumb. It is one of three thenar muscles. It has both a superficial part and a deep part.

Dorsal interossei of the hand

In human anatomy, the dorsal interossei (DI) are four muscles in the back of the hand that act to abduct (spread) the index, middle, and ring fingers away from hand's midline and assist in flexion at the metacarpophalangeal joints and extension at the interphalangeal joints of the index, middle and ring fingers.

HOXA13

Homeobox protein Hox-A13 is a protein that in humans is encoded by the HOXA13 gene.

Muscles of the hand

The muscles of the hand are the skeletal muscles responsible for the movement of the hand and fingers. The muscles of the hand can be subdivided into two groups: the extrinsic and intrinsic muscle groups. The extrinsic muscle groups are the long flexors and extensors. They are called extrinsic because the muscle belly is located on the forearm. The intrinsic group are the smaller muscles located within the hand itself. The muscles of the hand are innervated by the radial, median, and ulnar nerves from the brachial plexus.

Hand Extremity at the end of an arm or forelimb

A hand is a prehensile, multi-fingered appendage located at the end of the forearm or forelimb of primates such as humans, chimpanzees, monkeys, and lemurs. A few other vertebrates such as the koala are often described as having "hands" instead of paws on their front limbs. The raccoon is usually described as having "hands" though opposable thumbs are lacking.

Cooks syndrome

Cooks syndrome is a hereditary disorder which is characterized in the hands by bilateral nail hypoplasia on the thumb, index finger, and middle finger, absence of fingernails (anonychia) on the ring finger and little finger, lengthening of the thumbs, and bulbousness of the fingers. In the feet, it is characterized by absence of toenails and absence/hypoplasia of the distal phalanges. In the second study of this disorder, it was found that the intermediate phalanges, proximal phalanges, and metacarpals were unaffected.

Thumb hypoplasia is a spectrum of congenital abnormalities of the thumb varying from small defects to absolute retardation of the thumb. It can be isolated, when only the thumb is affected, and in 60% of the cases it is associated with radial dysplasia. Radial dysplasia is the condition in which the forearm bone and the soft tissues on the thumb side are underdeveloped or absent.

Triphalangeal thumb

Triphalangeal thumb (TPT) is a congenital malformation where the thumb has three phalanges instead of two. The extra phalangeal bone can vary in size from that of a small pebble to a size comparable to the phalanges in non-thumb digits. The true incidence of the condition is unknown, but is estimated at 1:25,000 live births. In about two-thirds of the patients with triphalangeal thumbs, there is a hereditary component. Besides the three phalanges, there can also be other malformations. It was first described by Columbi in 1559.

Radial dysplasia

Radial dysplasia, also known as radial club hand or radial longitudinal deficiency, is a congenital difference occurring in a longitudinal direction resulting in radial deviation of the wrist and shortening of the forearm. It can occur in different ways, from a minor anomaly to complete absence of the radius, radial side of the carpal bones and thumb. Hypoplasia of the distal humerus may be present as well and can lead to stiffness of the elbow. Radial deviation of the wrist is caused by lack of support to the carpus, radial deviation may be reinforced if forearm muscles are functioning poorly or have abnormal insertions. Although radial longitudinal deficiency is often bilateral, the extent of involvement is most often asymmetric.

Muscles of the thumb

The muscles of the thumb are nine skeletal muscles located in the hand and forearm. The muscles allow for flexion, extension, adduction, abduction and opposition of the thumb. The muscles acting on the thumb can be divided into two groups: The extrinsic hand muscles, with their muscle bellies located in the forearm, and the intrinsic hand muscles, with their muscles bellies located in the hand proper.

Hecht Scott syndrome is a rare genetic disease that causes congenital limb formation. The main characterisation is the aplasia or hypoplasia of bones of the limb. It is currently presenting in less than 1 in 1,000,000 newborns. It has been known to be more commonly present in males. It was first diagnosed in 2005 by Courtens et al. who recognised the malformations with his present case and four others that were similarly described in literature.

References

  1. 1 2 Innis, Jeffrey W; Pagon, RA; Bird, TD; Dolan, CR; Stephens, K (2006). "Hand-Foot-Genital Syndrome". GeneReviews. PMID   20301596.
  2. 1 2 Goodman FR, Bacchelli C, Brady AF, Brueton LA, Fryns JP, Mortlock DP, Innis JW, Holmes LB, Donnenfeld AE, Feingold M, Beemer FA, Hennekam RC, Scambler PJ (2000). "Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome". Am J Hum Genet. 67 (1): 192–202. doi:10.1086/302961. PMC   1287077 . PMID   10839976.
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