Hand-Foot-Genital Syndrome
Encyclopedia
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.
, 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.
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.
Radiographic findings
Urogenital Defects
Females may have the following:
Hallux
In tetrapods, the hallux is the innermost toe of the foot. Despite its name it may not be the longest toe on the foot of some individuals...
, 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
Apposition
Apposition is a grammatical construction in which two elements, normally noun phrases, are placed side by side, with one element serving to define or modify the other. When this device is used, the two elements are said to be in apposition...
of the thumbs. Urogenital abnormalities include abnormalities of the ureters and urethra
Urethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
and various degrees of incomplete Müllerian fusion
Müllerian duct
Müllerian ducts are paired ducts of the embryo that run down the lateral sides of the urogenital ridge and terminate at the Müllerian eminence in the primitive urogenital sinus. In the female, they will develop to form the Fallopian tubes, uterus, cervix, and the upper two-third of the vagina; in...
in females and hypospadias
Hypospadias
Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus...
of variable severity with or without chordee
Chordee
Chordee is a condition in which the head of the penis curves downward or upward, at the junction of the head and shaft of the penis. The curvature is usually most obvious during erection, but resistance to straightening is often apparent in the flaccid state as well. In many cases but not all,...
in males. Vesicoureteral reflux
Vesicoureteral reflux
Vesicoureteral reflux is an abnormal movement of urine from the bladder into ureters or kidneys. Urine normally travels from the kidneys via the ureters to the bladder...
, recurrent urinary tract infections, and chronic pyelonephritis
Pyelonephritis
Pyelonephritis is an ascending urinary tract infection that has reached the pyelum or pelvis of the kidney. It is a form of nephritis that is also referred to as pyelitis...
are common; fertility is normal.
Diagnosis, genetic basis and inheritance
Diagnosis is based on physical examination including radiographs of the hands and feet and imaging studies of the kidneys, bladderBladder
Bladder usually refers to an anatomical hollow organBladder may also refer to:-Biology:* Urinary bladder in humans** Urinary bladder ** Bladder control; see Urinary incontinence** Artificial urinary bladder, in humans...
, and female reproductive tract. HOXA13
HOXA13
Homeobox protein Hox-A13 is a protein that in humans is encoded by the HOXA13 gene.- Function :In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is...
is the only gene known to be associated with HFGS. Approximately 60% of mutations are polyalanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
expansions. Molecular genetic
Molecular genetics
Molecular genetics is the field of biology and genetics that studies the structure and function of genes at a molecular level. The field studies how the genes are transferred from generation to generation. Molecular genetics employs the methods of genetics and molecular biology...
testing is clinically available.
Hand-foot-genital syndrome is inherited in an autosomal dominant manner. The proportion of cases caused by de novo
De novo
In general usage, de novo is a Latin expression meaning "from the beginning," "afresh," "anew," "beginning again." It is used in:* De novo transcriptome assembly, the method of creating a transcriptome without a reference genome...
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.
Additional findings that might be present
Additional findings that may be present in HFGS according to the latest research are :- Limited metacarpophalangeal flexion of the thumb or limited ability to oppose the thumb and fifth finger
- Hypoplastic thenar eminences
- Medial deviation of the great toe (hallux varus), a useful diagnostic sign when present
- Small great toenail
- Fifth-finger clinodactylyClinodactyly-References:...
, secondary to a shortened middle phalanx - Short feet
- Altered dermatoglyphicsDermatoglyphicsDermatoglyphics is the scientific study of fingerprints. The term was coined by Dr. Harold Cummins, the father of American fingerprint analysis, even though the process of fingerprint identification had already been in use for several hundred years. All primates have ridged skin...
of the hands; when present, primarily involving distal placement of the axialAxialAxial may mean:* Along the same line as an axis of rotation in geometry* A type of modal frame in music* One of several anatomical directions in an animal body* Axial age, the period from 800 to 200 BC in China, India and the western world...
triradius, lack of thenar or hypothenar patterning, low arches on the thumbs, thin ulnar loops (deficiency of radial loops and whorls), and a greatly reduced ridge count on the fingers
Radiographic findings
- HypoplasiaHypoplasiaHypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
of the distal phalanx and first metacarpal of the thumbs and great toes - Pointed distal phalangesDistal phalangesThe distal or terminal phalanges are the terminal limb bones located at the tip of the digits...
of the thumb - Lack of normal tuftingTuftingTufting is a type of textile weaving in which a thread is inserted on a primary base.It is an ancient technique for making warm garments, especially mittens. After the knitting is done, short U-shaped loops of extra yarn are introduced through the fabric from the outside so that their ends point...
of the distal phalanges of the great toes - Fusions of the cuneiformCuneiformCuneiform can refer to:*Cuneiform script, an ancient writing system originating in Mesopotamia in the 4th millennium BC*Cuneiform , three bones in the human foot*Cuneiform Records, a music record label...
to other tarsal bones or trapeziumTrapeziumThe word trapezium has several meanings:* - a quadrilateral with one pair of parallel sides ....
-scaphoid fusion of the carpals - Short calcaneus
- Occasional bony fusions of the middle and distal phalanges of the second, third, fourth, or fifth toes
- Delayed carpal or tarsal maturation
- Metacarpophalangeal profile reflecting shortening of the first metacarpal, the first and second phalanges, and the second phalanx of the second and fifth digits
Urogenital Defects
Females may have the following:
- Vesicoureteral refluxVesicoureteral refluxVesicoureteral reflux is an abnormal movement of urine from the bladder into ureters or kidneys. Urine normally travels from the kidneys via the ureters to the bladder...
secondary to ureteric incompetence - Ectopic ureteral orificesOrifice of ureterThe orifices of the ureters are placed at the postero-lateral angles of the trigonum vesicae, and are usually slit-like in form.In the contracted bladder they are about 2.5 cm. apart and about the same distance from the internal urethral orifice; in the distended viscus these measurements may be...
- Trigonal hypoplasiaHypoplasiaHypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
- HypospadiacHypospadiasHypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus...
urethraUrethraIn anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine... - SubsymphysealSymphysisA symphysis is a fibrocartilaginous fusion between two bones. It is a type of cartilaginous joint, specifically a secondary cartilaginous joint.1.A symphysis is an amphiarthrosis, a slightly movable joint.2.A growing together of parts or structures...
epispadiasEpispadiasAn epispadias is a rare type of malformation of the penis in which the urethra ends in an opening on the upper aspect of the penis. It can also develop in females when the urethra develops too far anteriorly... - Patulous urethra
- Urinary incontinence
- Small hymenal opening
- Various degrees of incomplete Müllerian fusion with or without two cervices or a longitudinal vaginal septumVaginal septumA vaginal septum is a congenital partition within the vagina; such a septum could be either longitudinal or transverse.-Longitudinal septum – double vagina:...