A syndrome with characteristics of immune deficiency and neurological disorders in females and neonatal death in males. The syndrome has been described in only one family with nine affected individuals (five males and four females) spanning two generations. Symptomatic females present slowly progressive proximal muscle weakness, leg hyperreflexia, pes cavus, increased muscle tone in the legs, poor bladder function, static reduced night vision and frequent sinopulmonary infections associated with IgG2 deficiency. Males present with low birth weight and severe hypotonia that leads to death in the neonatal period. The gene locus has been mapped to Xq26-qter.

Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, and paraphasic errors, with minimal impairment of episodic memory; later stages are characterized by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 56 years. Dilated cardiomyopathy, amyotrophic lateral sclerosis, and Parkinson disease are now known to be part of the spectrum of findings associated with IBMPFD.

Myofibrillar myopathy-4 (MFM4) is an autosomal dominant disorder characterized by adult-onset distal muscle weakness primarily affecting the lower limbs at onset. Affected individuals usually present with gait difficulties in their forties, followed by slow progression with eventual involvement of the hands and proximal muscles of the lower limbs. Rare patients may develop cardiomyopathy. Skeletal muscle biopsy shows myopathic changes with myofibrillar changes (Selcen and Engel, 2005; Griggs et al., 2007). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).

Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis-1 (MMCKR1) is an autosomal recessive skeletal muscle disorder characterized by the onset of muscle cramping and stiffness on exertion in infancy or early childhood, although later (even adult) onset has also been reported. The features remit with rest, but some individuals develop mild proximal or distal muscle weakness. Rare affected individuals may demonstrate cardiac involvement, including left ventricular dysfunction or rhythm abnormalities. Laboratory studies show increased baseline serum creatine kinase levels with episodic spikes that may coincide with rhabdomyolysis. EMG shows myopathic changes, and muscle biopsy shows nonspecific myopathic or degenerative features (Lopes Abath Neto et al., 2021; Salzer-Sheelo et al., 2022). Genetic Heterogeneity of Myopathy with Myalgia, Increased Serum Creatine Kinase, and with or without Episodic Rhabdomyolysis MMCKR2 (620971) is caused by mutation in the DTNA gene (601239) on chromosome 18q12.