Ring Chromosome 14 Syndrome

A number sign (#) is used with this entry because of evidence that ring chromosome 14 (r14) syndrome is associated with a ring of chromosome 14 apparent on cytogenetic analysis, which may disrupt genes within this region.

Description

Ring chromosome 14 syndrome is characterized by early-onset epilepsy, developmental delay with mental retardation and poor speech, microcephaly, and dysmorphic facial features. Additional variable features include hypotonia and retinopathy (summary by Imataka et al., 2013 and Giovannini et al., 2013).

Clinical Features

Iselius et al. (1980) reported a 12-year-old girl who developed seizures at 8 months of age, followed by delayed psychomotor development with mental retardation and poor speech. She had some dysmorphic features, including broad, flat nose, synophrys, narrow palpebral fissures, high-arched palate, and cubitus valgus. She also had microcrania and poorly mineralized long bones and bones of the hand. Cytogenetic analysis showed a ring chromosome 14 that was not present in the mother; genetic material from the father was not available.

Schmidt et al. (1981) reported a 35-month-old girl of Puerto Rican descent with delayed psychomotor development, poor speech, and dysmorphic features, including high forehead, narrow biparietal diameter, flat occiput, flat nasal bridge, hypertelorism and downslanting palpebral fissures, epicanthal folds, short thick eyebrows, low-set ears with large lobes, high-arched palate, and short neck. She also had abnormal hypo- and hyperpigmented spots on the body. Neurologic examination showed poor head control and increased muscle tone with hyperreflexia; she later developed poorly controlled generalized tonic-clonic seizures. Cytogenetic studies identified a ring chromosome 14 aberration that was not present in either unaffected parent.

Matalon et al. (1990) reported a family in which a mother who was mosaic for a ring chromosome 14 transmitted it to her 2 sons, both of whom had severe mental retardation with poor or absent speech, infantile-onset seizures, and dysmorphic facial features. The mother had borderline normal cognition and mild dysmorphic features, including anteverted nares and downward slant to the eyes. The mother also had a translocation t(14q21q) that was not found in her sons; Matalon et al. (1990) postulated that the translocation contributed to the ring 14 formation.

Atchaneeyasakul et al. (1998) reported a patient (S.T.) with microcephaly, mild developmental delay, and chorioretinopathy associated with a ring chromosome 14.

Imataka et al. (2013) reported a 5-year-old girl who developed generalized seizures at age 9 months, followed by refractory complex partial seizures. She had delayed development and very mild facial abnormalities, including flat nose, blepharophimosis, and almond-shaped eyes. Brain MRI was normal; EEG showed high-amplitude slow waves with spikes. Chromosome analysis showed ring chromosome 14.

Giovannini et al. (2013) retrospectively reviewed the seizure phenotype of 22 patients with r(14) syndrome who ranged in age from 26 months to 22 years. The mean age at seizure onset was 1 year, 2 months, with 11 patients developing seizures before 6 months of age. Seizure type was variable, including generalized, tonic-clonic, myoclonic, clonic, and focal hemiclonic. Eight patients had severe and prolonged seizures resulting in status epilepticus. About half had seizures during sleep or while falling asleep. Most seizures were drug-resistant. Seizure frequency changed during the disease course, and some patients had some drug response. EEG tended to show slow background activity with paroxysmal spike-waves often during sleep. In addition to seizures, common features of these patients included axial hypotonia, microcephaly, and moderate to severe intellectual disability. Brain imaging showed nonspecific abnormalities in only some patients.