Split Hand/Foot Malformation - An overview

Introduction:

Split Hand/Foot Malformation is a rare genetic disorder that is present from birth, and it is also known as ectrodactyly. This condition is often associated with other syndromes or occurs isolated. Split Hand/Foot Malformation is characterized by limb malformations affecting the autopod. Autopod comes under the classification of limb, which refers to the hand and foot, including the fingers or toes, thumb, and palm or sole. This condition affects the central rays of autopod. It is a genetic condition inherited in an autosomal dominant pattern. This article will discuss Split Hand/Foot Malformation, its symptoms, causes, diagnosis, and treatment in detail.

What Is Split Hand/Foot Malformation?

The Spilt hand/foot malformation affects the autopod. It presents with an abnormal fissure or opening in the middle part of the limb or hand, complete or partial absence of digital, metatarsal, or metacarpal bones in the hand or feet, and fusion of remaining digits. There are two types of Split Hand/Foot Malformation: syndromic and non-syndromic. The syndromic form is often associated with another syndrome, and the non-syndromic condition occurs as an isolated involvement of the limbs. The severity of the symptoms differs for each individual.

What Causes Split Hand/Foot Malformation?

Multiple genetic defects can cause Split Hand/Foot Malformation, making it a genetic heterogeneity. This makes it difficult to diagnose the single genetic fault causing the condition. Split Hand/Foot Malformation is acquired in an autosomal dominant inheritance pattern and rarely by an autosomal recessive and X-linked pattern.

• Generally, a genetic disorder occurs due to an abnormal or harmful alteration in the DNA material. Autosomal inheritance refers to the presence of the altered gene in the 22 numbered pairs of non-sex chromosomes.
• For a genetic disorder, two mutated genes from each parent are necessary to cause the disease; however, in an autosomal dominant pattern, a single copy of the altered gene is sufficient to cause the disease.

Sometimes the condition can occur due to random alterations or mutations in the gene during embryonic development or fertilization. But in most cases, it occurs due to inherited genetic defects. It occurs due to the failure of the median ectodermal ridge (a specialized structure in the developing limb bud) during embryogenesis (human embryonic development).

The non-syndromic forms of Split Hand/Foot Malformation (SHFM) are described in six variant forms, and each variant is associated with an underlying genetic defect. The congenital abnormalities of each variant are:

• SHFM1 is associated with an abnormality in chromosome 7 (one of the 23 pairs of chromosomes).
• SHFM2 is associated with an abnormality in the X chromosome (One of the two sex chromosomes).
• SHFM3 is caused due to alterations in chromosome 10 at position 10q24.
• SHFM4 occurs due to genetic mutations in the gene TP63 (a protein-coding gene).
• SHFM5 is associated with chromosome 2.
• SHFM6 occurs due to genetic mutations in the gene WNT10B (protein-encoding gene).

Syndromic forms of Split Hand/Foot Malformation are often associated with other syndromes (A rare genetic condition affecting the skin, teeth, nails, kidney, hair, and other organs) such as:

• Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome (EEC).
• Ectrodactyly cleft palate syndrome.
• Ectrodactyly-fibular aplasia or hypoplasia syndrome.
• Ectrodactyly-Ectodermal dysplasia Macular-dystrophy syndrome.
• Ectrodactyly-polydactyly.

What Are the Symptoms of Split Hand/Foot Malformation?

The signs and symptoms of Split Hand/Foot Malformation occur in the first four weeks of life or between one to 23 months of age. The severity of the symptoms differs for each individual. The common signs and symptoms of Split Hand/Foot Malformation are:

• Presence of developmental defects that result in the decreased number of fingers or toes in hands and feet.
• An abnormal connection of two or more fingers gives a web-shaped appearance.
• The affected child has a complete absence of hand with no bony structures distal to the two bones of the forearm.
• The affected child may develop aniridia. Aniridia is an eye disorder with partial or complete absence of the iris (the colored tissue that contains the pupil at the center of the eye).
• Sensorineural hearing loss: The affected child may develop hearing loss in or both ears depending on the cochlear nerve abnormalities (auditory nerve responsible for hearing).
• Split-hand deformity: The individual develops split-hand deformity, which involves the absence of the middle parts of the hand, such as the fingers and metacarpals (five long bones of the hand). The severity of this condition may range from the absence of a middle finger to monodactyly (presence of a single digit) in hands.
• Split foot: Affected child may have an absence of the middle portion of the foot, such as the absence of middle toes and parts of the metatarsal bones five long bones of the foot). The severity of the condition ranges from mild deformity of the toes to complete absence of the second and third toes to monodactyl feet.

How Is Split Hand/Foot Malformation Diagnosed?

The clinician performs a detailed history-taking and physical examination of the affected child. The clinician assesses the familial history of the patient. A thorough analysis of the affected child is performed to determine the signs and symptoms of the patient. The most effective way to diagnose this condition is through radiographic investigation and physical examination.

The affected child may be referred for genetic testing to assess the genetic defects.

How Is Split Hand/Foot Malformation Treated?

Management of this condition is based on the symptoms of the affected child. Prosthetics are also recommended for the patients. But the most effective treatment option is surgical management. Surgical intervention such the reconstructive surgery is carried out to improve the appearance and the functional abilities of the affected with deformed limbs.

The parents are referred to genetic counseling to assess their genetic defects and the chances of passing down the condition to their children before planning for a pregnancy. Antenatal diagnosis of the disease can be made during pregnancy through ultrasound radiography.

Conclusion:

Split Hand/Foot Malformation is a rare genetic condition characterized by limb deformities. It is a genetic heterogeneity condition with variable genetic defects causing the condition. It is most commonly inherited in an autosomal dominant pattern and rarely in X-linked and autosomal recessive patterns. The condition causes an abnormal cleft appearance at the center of the hands and missing digits. They are most often associated with other syndromes. The effective treatment method is the surgical intervention to improve the functionalities and appearance of the patient.