An Unexpected Cause of Ptosis: 22q11.2 Duplication Syndrome
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.310061
Source of Support: None, Conflict of Interest: None
Keywords: Duplication syndrome, microarray analysis, ptosis
The 22q11.2 duplication syndrome is characterized by mild dysmorphic features, learning disabilities, velopharyngeal insufficiency with or without cleft palate, and heart defects.Autism spectrum disorders, epilepsy, hyper nasal speech, urogenital abnormalities, and ocular abnormalities are frequently reported in patients with 22q11.2 duplication syndrome.,
Even within families carrying the same duplication, expression of these features is variable. Although some patients are mildly affected with intellectual disability and minor dysmorphic features, others presented with severe congenital anomalies. Early and precise diagnosis of the condition is imperative to provide adequate genetic counseling.
We report here a case of 22q11.2 duplication syndrome presented with ptosis. To our knowledge, this is the first clinical report of ptosis associated with 22q11.2 duplication syndrome in a patient with no additional features.
A 16-month-old female patient was admitted to hospital with bilateral ptosis. She was the first child of consanguineous parents. Family medical history of the patient was unremarkable. She was born full-term after a normal pregnancy by vaginal delivery.
On physical examination, her weight, length, and head circumference were appropriate for her age. Neurologic examination was normal, except for bilateral severe ptosis [Figure 1]. She had good head control at one month. She could sit without support at 6 months. She could walk at 15 months. She has normal cognitive development. There were no organomegaly and dysmorphic features. Ophthalmologic examination was normal.
Hemoglobin level, serum electrolytes, and creatinine kinase were normal. Cranial magnetic resonance imaging was normal. Echocardiogram revealed no abnormality. Congenital myasthenic syndromes were suspected, and electromyography was performed. Electromyography with repetitive nerve stimulation of the hypothenar muscle was normal.
For copy number variations, chromosome microarray analysis was performed using the Affymetrix GeneChip Cytoscan Optima (ThermoFisherScientic, USA). The patient was found to have a de novo 2.8 Mb duplication at 22q11.21. The microarray analysis was reported as arr[hg19] 22q11.21 (18,917,030–21,804,886) X3. The pathogenic, gain copy number variations includes “22q11 duplication syndrome region” and contains 41 OMIM genes: PRODH, DGCR2, DGCR14, TSSK2, GCS2, SLC25A1, CLTCL1, HIRA, MRPL40, UFD1L, CDC45, CLDN5, SEPT5, GP1BB, TBX1, GNB1L, TXNRD2, COMT, ARVCF, DGCR8, TMT2A, RANBP1, ZDHHC8, RTN4R, DGCR6L, RIMBP3, ZNF74, SCARF2, MED15, PI4KA, SERPIND1, SNAP29, CRKL, LZTR1, THAP7, P2RX6, SLC7A4, BCRP2, RIMBP3C, RIMBP3B, and HIC2. Parental chromosome microarray analyses were normal.
During the 20 months follow-up period, at the age of three years, the patient showed normal psychomotor development. Her psychomotor development was evaluated using the Denver developmental screening test-II (Turkish version). Four areas (fine motor adaptive, gross motor, personal-social, and language) of functioning were assessed. The result of Denver developmental screening test-II shows that the patient is within the normal and appropriate developmental growth for her age.
Ptosis occurs in isolation or concurrently as an ocular or neurologic disease [Table 1]. Most cases of congenital ptosis unilateral and about 20–70% of patients will develop amblyopia. From history and examination, a differential diagnosis of ptosis was considered in our patient. Cranial magnetic resonance imaging and electromyography were normal. Chromosome microarray analysis was performed, and we describe a patient of 22q11.2 duplication syndrome presenting with bilateral ptosis who has normal psychomotor development.
Chromosome 22q11 is one of the most unstable parts of the human genome by the presence of chromosome-specific low-copy repeats or segmental duplications. The 22q11.2 duplication is also associated with a wide variety of phenotypes. Several possibilities may account for phenotypic variability including variation in genetic background, additive pathogenic mutations, epigenetic factors, gene expression level, and regulatory variation among genes in rearranged regions.,
The reported clinical findings in the 22q11.2 duplication syndrome are behavioral problems, intellectual disabilities, hearing loss, growth and developmental delay, hypotonia, microcephaly, pachygyria, seizures, urogenital anomalies, T cell deficiency, and congenital heart defects. The dysmorphic features detected are hypertelorism, broad flat nose, micrognathia, velopharyngeal insufficiency, dysplastic ears, epicanthal folds, down-slanting palpebral fissures, long narrow face, and brachydactyly.,
The ocular abnormalities in 22q11.2 duplication syndrome are common. Refractive errors, strabismus, amblyopia, retinal vascular tortuosity, glaucoma, abnormal eye movements, and ptosis are reported in children with 22q11.2 duplication syndrome. In Forbes et al. study, they found that over half of children with 22q11.2 duplication syndrome have ocular abnormalities. Our patient's ophthalmologic examination was normal except bilateral ptosis. To our knowledge, bilateral ptosis and normal psychomotor development with 22q11.2 duplication syndrome have not been described.
The 22q11.2 duplication syndrome should be considered in the differential diagnosis of ptosis. It is important that early recognition of this syndrome for modifying the course of the illness and optimizing patient outcome. The variety of clinical manifestations of this syndrome indicates that a multidisciplinary approach is necessary for diagnosis, treatment, and follow-up of these patients. The 22q11.2 duplication syndrome may be difficult to recognize and diagnose in some patients because of broad phenotypic variability. This case report contributes to an expanding clinical spectrum of patients with 22q11.2 duplication syndrome.
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