Introduction
Fetal akinesia deformation sequence (FADS) or Pena-Shokeir phenotype is a rare genetically heterogeneous disorder (a disorder caused by several genes) in which there are decreased intrauterine fetal movements because of the short umbilical cord and developmental abnormalities such as arthrogryposis (multiple joint contractures or stiffness), facial anomalies, intrauterine growth restriction, and pulmonary hypoplasia (incomplete development of lungs). At least 20 specific familial types are recognized based on family history, pregnancy history, natural history, and pathologic studies. It has a prevalence of fewer than one per 1,000,000 births, with an autosomal recessive mode of inheritance.
What Are the Clinical Features of Fetal Akinesia Deformation Sequence?
Most babies are born prematurely. If they survive, they may have growth delay and malabsorption. The transmission pattern of FADS has consistent autosomal recessive inheritance (a genetic trait passed down from parent to child, and usually, parents do not have the condition). Pathogenetic mechanisms include neuropathy (nerve damage), muscular disorders, neuromuscular junction disorders, maternal myasthenia gravis (an autoimmune disorder in which antibodies destroy nerves and muscles, which causes the weakening of skeletal muscles), and restrictive dermopathy (skin disorder).
The clinical features include:
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Pulmonary hypoplasia occurs due to a lack of movement of the diaphragm and intercostal muscles.
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Ulnar deviation of hands in which the joints in the wrist and hand shift so that the fingers bend toward the ulna bone on the outside of the forearm.
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Rocker bottom feet in which the middle of the foot touches the floor while the toes and heels curve upwards.
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Camptodactyly, the fingers are bent in the middle joint and cannot be fully straightened.
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Sparse dermal ridges and an absence of palmar flexion creases.
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The mouth is small with micrognathia, a high-arched palate, and occasionally a cleft palate.
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The face is expressionless with hypertelorism (increased distance between two body parts) and telecanthus (increased distance between the inner corners of your eyelids), and ears are small, poorly folded, and angulated posteriorly.
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Short neck.
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Cryptorchidism (undescended testicle).
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Cardiac defects.
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A short gut syndrome is a condition in which the fetal body cannot absorb enough nutrients from food because of the small intestine size.
What Is the Etiology of Fetal Akinesia Deformation Sequence?
The etiology of the fetal akinesia deformation Sequence includes:
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Neurological Etiology - Defects in motor system pathways of the central or peripheral nervous system, spinal cord, peripheral nerves, and neuromuscular junction and can cause cerebral and cerebellar dysgenesis, spinal tract, myelin, and end plate disturbances, which results in interference with normal movement in utero. In addition, ischemia can cause loss of neuron function, and central hypotonia can cause contractures.
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Myopathic Etiology - Muscle fibers (smooth and cardiac muscles) fail to develop, causing dystrophies and dysplasias. Muscle components can differ, the craniofacial muscle can differ from body muscle, and restrictive dermopathy and skeletal musculature may occur.
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Connective Tissue Etiology - It can cause chondrodysplasias, restrictive skin, joint limitation, laxity, and fetal edema, which can limit the movement of the fetus intrauterine.
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Other Causes Include -
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Ischemia due to vascular compromise, trauma, drugs, infection, hypotension, maternal illness, and thrombophilia.
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Maternal asymptomatic myasthenia gravis, maternal cocaine use, and maternal antibodies can cause loss of movement in the uterus.
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What Is the Diagnosis of Fetal Akinesia Deformation Sequence?
The diagnosis of Fetal Akinesia Deformation Sequence includes:
Prenatal diagnosis using ultrasonography and magnetic resonance imaging (MRI) are used. Abnormalities can be detected as early as 12 weeks of gestation and should include the identification of the following:
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Cystic hygroma (sac-like structure near head or neck area).
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Increased nuchal translucency (fluid behind the fetal’s neck).
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Nuchal edema (tissue swelling in the back of the neck of the fetus).
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Hydrops fetalis (abnormal fluid buildups in some areas of the fetus's body).
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Arthrogryposis.
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Subcutaneous edema.
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Pterygia (growth of the conjunctiva or mucous membrane that covers the white part of the eye) and other structural abnormalities.
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Lack of extremity motions.
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The persistent abnormal posture of the limbs.
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Lack of facial movements.
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Polyhydramnios due to decreased fetal swallowing.
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Pulmonary hypoplasia.
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Short umbilical cord due to decreased fetal movements.
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Intrauterine growth restriction (IUGR).
MRI can be useful in central nervous system findings, which include:
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Agenesis of the corpus callosum.
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Lissencephaly (brain malformation characterized by the absence of folds in the cerebral cortex).
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Hydrocephalus (abnormal buildup of cerebrospinal fluid in the deep cavities of the brain).
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Spinal cord abnormalities.
Genetic analysis of mutations in the neuromuscular junction genes such as CHRNG, CHRNA1, CHRND, CNTN1, RAPSN, DOK7, and SYNE1 should be identified which may be a pathogenetic cause of FADS. Also helps in the differential diagnosis.
What Are the Differential Diagnosis of Fetal Akinesia Deformation Sequence?
The differential diagnosis of fetal akinesia deformation Sequence includes:
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Trisomy 18 syndrome.
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Cerebro-oculo-facial syndrome.
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Congenital myopathies.
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Congenital myasthenia gravis.
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Glycosylation type 1A deficiency.
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Infantile Pick’s disease.
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Lethal Larsen syndrome.
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Lethal pterygium syndromes.
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Lissencephaly III.
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Neu-Laxova syndrome.
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Phosphofructokinase deficiency (glycogenosis VII).
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Potter syndrome.
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Restrictive dermopathy.
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Walker-Warburg syndrome.
What Is the Prognosis of Fetal Akinesia Deformation Sequence?
The fetus diagnosed with FADS has a poor prognosis; most reported cases die in the uterus, at birth, or in the newborn period, mostly because of severe pulmonary hypoplasia. Therefore, termination of pregnancy should be considered after diagnosis. Despite excellent neonatal respiratory support, early death can happen due to the failure of lung maturation and function due to a lack of gastrointestinal maturation, a short functional gut and major feeding difficulties can occur. In addition, genetic (failure of normal gene action) and environmental interference (including maternal medications), with normal developmental processes, may lead to the failure of the embryo or fetus to develop normal movements, and the families should receive adequate counseling.
What Is the Treatment of Fetal Akinesia Deformation Sequence?
If diagnosed in the antenatal period, late termination of pregnancy by comfort care post-delivery or full resuscitative intervention post-delivery can be considered a management option. Despite poor survival after delivery, newborns should receive complete resuscitation, administration of antimicrobials and vasopressors /inotropes, oral, nasal airways, laryngeal airways, endotracheal tube, and fiber optic or video laryngoscope and gastrotomy tube should be given. Even after all the efforts, the newborn may have respiratory distress because of pulmonary hypoplasia, intubation may be difficult because of micrognathia and short neck, and feeding is difficult because of impaired swallowing. Therefore specific treatment is not available, and management is largely supportive. However, even after the continuation of pregnancy, 30 percent of fetuses die in the uterus or die after birth, mainly due to pulmonary hypoplasia.
Conclusion
FADS is a rare genetic disorder with a poor prognosis. Diagnosis can be made with the help of imaging modalities, and can be detected around 12 weeks of gestation. Pregnancy termination should be initiated if diagnosed in the antenatal period. In addition, parents with the affected child should undergo detailed counseling about risks and plans for further pregnancies.
