Dyke-davidoff-masson syndrome: A case report of an adolescent boy at a tertiary hospital in Adamawa, North-Eastern Nigeria.

Dyke-Davidoff-Masson Syndrome (DDMS) is a rare clinical condition in which atrophy or hypoplasia of one cerebral hemisphere occurs secondary to brain insult during fetal or early childhood, which results in variable clinical manifestations like hemiparesis, seizures, expressive aphasia, and mental retardation. This rare entity mainly presents in childhood and is unusual in adults. DDMS is a rare cause of epilepsy and should be considered and excluded in cases of refractory seizures. Few cases have been reported from a developing nation like Nigeria but not from the north-eastern part of Nigeria to the best of our knowledge. Though fewer specialists exist in Adamawa State, efforts to train more specialists and education of medical officers to manage this rare case need to be strengthened. Herein is a case of an adolescent boy with recurrent generalized tonic-clonic convulsions complicated by left-sided hemiparesis, expressive aphasia, and mental age equivalent of a six-year-old by the Goodenough draw-a-person test. Found to be obese with Body Mass Index (BMI) of 29 kg/m2 (Z-score >2 Standard deviation SD), microcephaly, Occipito-frontal Circumference (OFC) of 45 cm (Z-score > -3 SD), spastic left-sided hemiplegia and hemiplegic gait. Magnetic resonance imaging (MRI) of the brain showed hyper-intensity in the right cerebral hemisphere, extensive atrophy of the right cerebral hemisphere involving the ipsilateral fronto-temporoparietal lobes, cerebral peduncle, and a contralateral megalencephaly, ipsilateral lateral ventricular dilatation, hypertrophic calvarium, hyperpneumatization of sphenoidal sinuses and midline shift due to loss of volume on the right. A diagnosis of Dyke-Davidoff-Masson syndrome was made; the patient did well on carbamazepine and physiotherapy. Caregivers were counseled, and the patient was discharged home and is currently on a follow-up visit.

Mutational spectrum of the TYR and SLC45A2 genes in Pakistani families with oculocutaneous albinism, and potential founder effect of missense substitution (p.Arg77Gln) of tyrosinase.

BACKGROUND: Oculocutaneous albinism (OCA) is an autosomal recessive disorder of abnormal melanin formation, which results in hypopigmentation of skin, hair and eyes. OCA is classified into four types based on clinical and genetic findings. OCA1 is the most severe form of albinism, and is caused by mutations in the tyrosinase (TYR) gene, while OCA4 is caused due to mutations in SLC45A2. METHODS: In total, 13 families with ≥ 3 members with OCA were enrolled. Family history was ascertained and pedigrees were drawn up. Blood samples were collected and processed for DNA extraction. Linkage analysis was performed by typing three short tandem repeat markers in candidate regions of TYR and SLC45A2. Sequence analysis was performed of all the coding exons and adjacent intronic sequences of both genes. RESULTS: Eight families showed linkage to OCA1 and one family showed linkage to OCA4. Four missense substitutions (p.Arg239Trp, p.Ser192Tyr, p.Ser44Arg and p.Arg77Gln) were identified in TYR in the families with OCA1 linkage, and another missense substitution (p.Gln272Lys) was identified in the family with OCA4 linkage. One of the identified missense substitution (p.Arg77Gln) in TYR was found in five different families, which had a common haplotype. CONCLUSIONS: We identified four missense substitutions in TYR and a single missense substitution in SLC45A2. One missense substitution (p.Arg77Gln) in TYR was found in five different families that originated from the same geographical area and displayed a common haplotype, suggesting a single origin that then spread to different geographical areas of Azad Kashmir, Pakistan.

Identification of a novel mutation (p.Ile198Thr) in gene TYR in a Pakistani family with nonsyndromic oculocutaneous albinism.

The TYR gene (MIM #6069333) is located at position 11q14.3 on the human chromosome, and encodes tyrosinase, which is expressed in melanocytes and controls the biosynthesis of melanin. Most TYR mutations eliminate the activity of tyrosinase, preventing melanocytes from producing any melanin throughout life. People with this form of albinism have white hair, light-coloured eyes and very pale skin. Some mutations in TYR reduce but do not completely eliminate tyrosinase activity, and allow some melanin to be produced. We report a Pakistani family with four members affected by oculocutaneous albinism (OCA). Blood samples were collected from all affected individuals, normal siblings and their parents. Genomic DNA was extracted, and sequence analysis of all the coding exons and adjacent intronic sequences of TYR was performed, which identified a novel missense substitution (p.Ile198Thr). Sequencing of TYR in 90 unrelated healthy individuals showed no sequence variant at this location. Our study expands the mutational spectrum of OCA1.