The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a 'fingerprint' profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with CLN3 (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730).

Isolated complex I deficiency is a rare inborn error of metabolism due to mutations in nuclear or mitochondrial genes encoding subunits or assembly factors of the human mitochondrial complex I (NADH: ubiquinone oxidoreductase) and is characterized by a wide range of manifestations including marked and often fatal lactic acidosis, cardiomyopathy, leukoencephalopathy, pure myopathy and hepatopathy with tubulopathy. Among the numerous clinical phenotypes observed are Leigh syndrome, Leber hereditary optic neuropathy and MELAS syndrome (see these terms).

Combined oxidative phosphorylation deficiency type 3 is an extremely rare clinically heterogenous disorder described in about 5 patients to date. Clinical signs included hypotonia, lactic acidosis, and hepatic insufficiency, with progressive encephalomyopathy or hypertrophic cardiomyopathy.

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in the first or second decade, before the end of puberty (summary by Delatycki et al., 2000). For a general phenotypic description of Friedreich ataxia (FRDA), see FRDA1 (229300), which is caused by mutation in the FXN gene (606829) on chromosome 9q13.

Any hypertrophic cardiomyopathy in which the cause of the disease is a mutation in the TNNC1 gene.

CMH27 is a severe, early-onset cardiomyopathy with morphologic features of both dilated and hypertrophic disease, characterized by biventricular involvement and atypical distribution of hypertrophy. Heterozygotes are at increased risk of developing cardiomyopathy (Almomani et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of hypertrophic cardiomyopathy, see CMH1 (192600). An oligogenic form of hypertrophic cardiomyopathy, involving heterozygous mutations in the ALPK3, TTN (188840), and MYL3 (160790) genes has also been reported in 1 family.

Familial hypertrophic cardiomyopathy-28 (CMH28) is characterized by asymmetric septal hypertrophy, atrial fibrillation and nonsustained ventricular tachycardia, and risk of sudden death. Dyspnea is the most common symptom, but more than half of affected individuals are asymptomatic. Hypertrabeculation of the left ventricle with noncompaction has been observed in some patients (Ochoa et al., 2018). For a general phenotypic description and discussion of genetic heterogeneity of familial hypertrophic cardiomyopathy, see CMH1 (192600).