|Year : 2019 | Volume
| Issue : 2 | Page : 125-127
Type (0) spinal muscular atrophy associated with fractures at birth
Ashish Jain, Brajesh Kumar Jha, Abhishek Chopra
Department of Neonatology, LNJP and Allied Hospital, Maulana Azad Medical College, New Delhi, India
|Date of Web Publication||25-Apr-2019|
Dr. Ashish Jain
601 A, Sukhsagar Apts, Plot No. 12, Sector 9, Dwarka, New Delhi - 110 075
Source of Support: None, Conflict of Interest: None
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis. In addition to the three classical SMA types mentioned worldwide, a new form known as Type 0 with intrauterine onset in the form of fetal akinesia and profound hypotonia manifesting as birth asphyxia and a progressive, and early fatal course has been described. Here, we report a case of Type 0 SMA presenting with bilateral symmetrical fracture of long bones at birth, which has been reported miniscule in the world literature.
Keywords: Fetal akinesia, fractures at birth, Type (0) spinal muscular atrophy
|How to cite this article:|
Jain A, Jha BK, Chopra A. Type (0) spinal muscular atrophy associated with fractures at birth. J Clin Neonatol 2019;8:125-7
| Introduction|| |
Bilateral symmetrical fracture of long bones is a relatively rare situation in neonates. It usually occurs after the newborn period either during childhood or later in life. A newborn with multiple fractures is thought to have osteogenesis imperfect (OI) at a first look. Multiple fractures can be associated with trauma as well as a number of inherited bone dysplasias and metabolic disorders. The present case was diagnosed as spinal muscular atrophy (SMA) Type (0) based on age of presentation, symmetrical pattern of fractures of bones, family history substantiated by histopathological examination, and genetic studies.
| Case Report|| |
A term male infant was admitted to our neonatal unit with severe birth asphyxia and bilateral symmetrical fracture of humerus and femur. He was born vaginally with episiotomy with breech presentation to gravida 4, para 3, live 1 mother at 38-week gestation through clear liquor. During late trimester of antenatal period, mother perceived decreased fetal movements. Not much investigated antenatally except a single antenatal USG done at 38 weeks, had findings of polyhydramnios (AFI = 42 cm) with fetal limbs in extended posture. There was second-degree parental consanguinity and history of death of two siblings in early neonatal life. The first pregnancy was uneventful resulting in delivery of a full-term male baby, currently 8 years old and is healthy. Second and third pregnancies ended with delivery of male babies, both expired at 1 h and 72 h of life, respectively. Although no papers are available, as per history from parents, babies had asphyxia and meconium aspiration. The proband infant had a birth weight of 2720 g requiring resuscitation up to and in the form of tube and bag ventilation with Apgar scores of 3, 4, and 4 at 1, 5, and 10 min of life, respectively. He was ventilated soon after birth and never weaned off in view of nil respiratory efforts and comatose sensorium. The baby had generalized hypotonia with no spontaneous movement during whole stay at neonatal intensive care unit. Physical examination revealed dysmorphism in the form of small forehead, broad nasal bridge, prominent nasolabial folds, tapering fingers with secondary arthrogryposis, and B/L undescended testes. There was excessive pooling of oral secretions requiring frequent oral suctioning reflecting poor gag. Radiographic examination documented symmetrical fractures of the femur and humerus [Figure 1]. Scan for other anomalies was negative except for mild dilatation of lateral, IIIrd and IVth ventricles. Biochemical tests revealed total creatine phosphokinase (CPK) 1730 IU/L with CPK (MB) 1663 IU/L. Metabolic workup was insignificant. Histological examination of the muscle tissue showed numerous atrophic muscle fibers in each muscle fascicle along with hypertrophied muscle fibers with predominance of Type II fibers on immunohistochemical analysis for myosin part. Atrophy and hypertrophy of both Types I and II fibers were found. Findings were consistent with SMA Type I. Genetic studies revealed homozygous deletion of exon 7 of SMN1 gene. The baby died at 73 h of age of multiorgan dysfunction due to severe birth asphyxia. Parents were counseled in detail regarding the genetic nature of the disease and the chances of recurrence of this condition in future pregnancies. Furthermore, the need for prenatal screening was discussed.
| Discussion|| |
SMA is the most common genetic cause of infant mortality, affecting approximately 1 in 10,000 live births. It is due to homozygous deletions or mutations in the SMN1 gene on chromosome 5q13. Cessation or decreased perception of fetal movements along with polyhydramnios as in the present case is reported in the medical literature. Polyhydramnios is associated with 2- to5-fold increase in the risk of perinatal mortality.
In newborns, the differential diagnosis of multiple fractures comprises only few entities. The most common disorder is OI. Generalized osteoporosis with under-ossified skull and spine, anisospondyly, multiple long bone, and rib fractures make the diagnosis of OI usually easy.
The heterogeneous group of lethal gracile bone dysplasias is characterized by distinctive facial dysmorphology, moderately short limbs, small hands, and feet. Absence/aplasia of the spleen is a distinctive feature. The diagnostic radiographic findings include extremely slender tubular bones (fishbone diaphyses), flared tubular bones, and undermineralized skull simulating cloverleaf skull.
Multiple fractures with slender bones are features of oligohydramnios deformation syndrome (ODS) and fetal akinesia deformation sequence (FADS). Both are results of akinesia – primary in ODS and secondary in FADS. Both are characterized by a short umbilical cord, limb positional deformities, and pulmonary hypoplasia. ODS is caused by oligohydramnios, and FADS is the result of neuromuscular disorders. Multiple rib fractures are characteristic of achondrogenesis Type IA. The most common single fracture of the clavicle may occur during traumatic delivery.
The absence of fetal movements is an important forewarning sign of a most likely musculoskeletal abnormality. In our case, symmetry of fractures in a hypotonic newborn was consistent with the diagnosis of FADS. The differential diagnosis of FADS disorders comprises (1) SMA Type 0 (Werdnig–Hoffmann disease [WHD]), (2) arthrogryposis multiplex congenital syndromes (AMCSs), and (3) congenital myotonic dystrophy (CMD). WHD Type (0) denotes most severe form of the disease such as in our patient. The reported severe SMA Type (0) presented with reduced fetal movements in utero, profound hypotonia, severe asphyxia, and respiratory insufficiency at birth warranting resuscitation and mechanical ventilatory support. Types 2 and 3 denote forms with later onset and less dramatic course. AMCS is characterized by fixed position of multiple joints with limitation of movement. CMD shares pregnancy characteristics – polyhydramnios and absence of fetal movemets – with WHD. Neonatal hypotonia, facial diplegia, and arthrogryposis of the lower extremities are distinctive clinical features of CMD. Impaired swallowing, aspiration, and respiratory complications result in early fatal outcome. [Table 1] shows a set of clinical conditions presenting with fractures at birth.
| Conclusion|| |
SMA Type (0) should be kept as a differential diagnosis for fractures at birth with antenatal history of decreased fetal movements and polyhydramnios. The present case is different from previous case reports of SMA Type (0) due to the presence of fractures at birth.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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