Abstract
Cornelia de Lange syndrome is a genetic disorder with multiple system abnormalities. It is especially characterized by typical facial appearance and hirsutism. Growth and mental retardation, gastrointestinal, cardiovascular, and orthopedic abnormalities are other important features of this syndrome. In this case, we present a rare manifestation of Cornelia de Lange syndrome with a unilateral pes equinovarus deformity without other more specific orthopedic manifestations. Ponseti method's was applied as the initial procedure. Afterwards, complete subtalar release was performed. After four years follow-up, clinical and radiological results were satisfactory. Unilateral pes equinovarus deformity may be a part of this syndrome as well as a sporadic presentation. The discrimination is important for anesthetic procedures and surgical outcomes.
Keywords: Cornelia de Lange, Pes equino varus, Congenital deformity
1. Introduction
Cornelia de Lange syndrome (CdLS) is a genetic disorder with multiple system abnormalities. It is especially characterized by typical facial appearance and hirsutism. Growth and mental retardation, gastrointestinal, cardiovascular, and orthopedic abnormalities are other important features of this syndrome.1,2 In a recent study, Liu et al. reported this syndrome as a cohesinopathy that is caused by alterations of cohesion function.3
The features of this disorder vary widely among affected individuals and range from relatively mild to severe. Van Allen et al. suggested a classification system based on the clinical variability in CdLS. According to this classification; CdLS with characteristic facial and skeletal changes was labeled as type I or classic type, CdLS with typical facial features but minor skeletal anomalies was labeled type II or mild type; when phenotypic manifestations are found in the presence of chromosomal aneuploidy or after teratogenic exposure, the condition is referred as type III.4
It is a rare syndrome recognized on the basis of a characteristic facial appearance including microcephaly, micrognathia, synophrys, long eyelashes, long philtrum, short upturned nose, and thin downturned lips. Hirsutism, hearing impairments, low set ears, vision abnormalities, seizures, and heart abnormalities (ventriculoseptal or atrial septal defects) are also common.5, 6, 7 The orthopedic manifestations of the syndrome include oligodactyly, clinodactyly and simian line in upper extremities, hip dislocation or dysplasia, scoliosis, tight Achilles tendons, and delayed maturation of bone.5,8 Radial aplasia and bilateral pes equinovarus (PEV) are other rare abnormalities.7
In this case, we present a rare manifestation of CdLS with a unilateral PEV deformity without other more specific orthopedic manifestations.
2. Case report
Two months of girl with growth retardation and foot deformity was brought to our hospital by her parents. She was the third child after two healthy brothers, born of a 38 weeks gestation, uneventful vaginal delivery and she weighted 3100 g at birth. It was a non-consanguineous marriage and PEV deformity was diagnosed prenatally. She was already diagnosed as CdLS in another medical center after a genetic investigation. Chromosomal analysis was done on peripheral blood lymphocytes according to conventional techniques. The analysis revealed a normal female karyotype (46, XX).
In her physical examination; she had 3400gr (<3p) weight, 53cm height (<3p), a head circumflex of cm (39 cm, <3 SD). She had characteristic facial dysmorphia including, microcephaly, synophrys, long philtrum, low hair lines, and excess hair on the forehead (Fig. 1). Stenosis of upper respiratory tract, gastro esophageal reflux and pulmonary hypoplasia were not determined. Ophthalmologic examination revealed normal findings. On cardiac examination 1/6 pansystolic murmur was osculated. As orthopedic manifestation, there was only unilateral (left) PEV deformity (Fig. 2). In her systemic examination, there were no other serious findings except retardation in motor development.
Fig. 1.
Characteristic facial dysmorphia.
Fig. 2.
PEV deformity before treatment.
Her biochemical measurements were normal except nutritional anemia. Chest x-ray revealed normal findings. Abdominal ultrasound and echocardiographic evaluations showed no abnormal findings. Left talocalcaneal antero-posterior and lateral angles were decreased at radiographies (Fig. 2).
For PEV deformity, we started casting with Ponseti method. We changed the casts every 4 or 5 days. Since the deformity was not corrected we planned a surgical procedure (total complete subtalar release) when the baby was seven months old. Before the surgery nutritional anemia was treated with erythrocyte transfusion. Inhalation anesthesia was performed. Surgery duration time was 95 minutes. At the surgery; Achilles tendon, finger flexor muscles consisted of FHL and FDL, and tibialis posterior muscle were Z lengthened, and tibio-talar, subtalar, and talo-navicular joint capsules, and all fibrotic and strong ligaments were released. After the surgery, long leg cast was applied and the patient was discharged at post operative fifth day. The cast was removed 6 weeks after the surgery and splint treatment was applied for six months. After 4 years of follow up, the patient's foot was healed successfully, and her functional outcome was of satisfactory (Fig. 3). The child was walking in normal shoes.
Fig. 3.
Clinical appearance of the foot at post-operative 4 years.
3. Discussion
CdLS is a rare developmental disorder that affects many parts of the body. The features of this disorder vary widely among affected individuals and range from relatively mild to severe.5 Our case was a mild presentation of CdLS (type II). She did not have any severe systemic deformities. Our clue to the diagnosis was her distinctive facial features and growth retardation. This characterized facial dysmorphia included microcephaly, micrognathia, synophrys, long eyelashes, long philtrum, short upturned nose, low set ears, hirsutism, and thin downturned lips.
PEV is a multifactorial clinical disorder. Environmental factors, genetics, intrauterine mechanical factors, neuromuscular disorders, muscular imbalance, local dysplasia, infections, and myodysplasia are all reported to be responsible for this disorder.9 On the other hand, it is observed in many genetic syndromes including Meckel-Gruber syndrome, Fetal Hydantoin syndrome and CdLS.
Most common orthopedic manifestations of this syndrome include involvement of the upper extremities and Achilles tendon respectively.7 Although upper extremity abnormalities like short forearms, small hand with short metacarpals or short tapering fingers are very common orthopedic manifestations, we didn't observed any of these abnormalities in our patient.5
PEV deformity is a common congenital disorder seen in childhood. The unilateral form has not been reported in CdLA syndrome before.5,7 This deformity could be a rare manifestation of CdLA syndrome; however it could also be specified as a sporadic PEV deformity together with CdLA syndrome. Therefore, it is not possible to discriminate these two presentations. Whichever it is, most important thing is to start the treatment urgently with Ponseti method. Surgery may be performed later if needed.10 This discrimination is consequential for recurrence of the deformity after the surgery and also for anesthetic procedures. A detailed preoperative planning is very fundamental, since the stenosis in upper respiratory tract and micrognathia could yield difficulties during intubation and it is crucial to decide the anesthesia procedure.
To our knowledge, it is the only case that includes isolated unilateral PEV without other more specific orthopedic deformities in CdLA syndrome. Unilateral PEV deformity may be a part of the syndrome as well as a sporadic presentation. The discrimination is important for anesthetic procedures and surgical outcomes.
Disclosure of funding and conflict of interest
Each of the authors states that there is no funding and conflict of interest about this manuscript.
Author Contribution
Serkan Erkuş, M.D. (Contribution: Study design, manuscript preparation, performed measurements).
Turgut Ali, Assoc. Prof. (Contribution: Study design and conception, manuscript preparation, acquisition-analysis of data, statistical analysis, critical review).
Onvural Burak, MD (Contribution: Study design and conception, manuscript preparation, statistical analysis, critical review).
Kalenderer Onder, Assoc. Prof. (Contribution: Study design and conception, manuscript preparation, statistical analysis, critical review).
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