TABLE 4.

Common Recognizable XLID Syndromes

Syndrome	Common Manifestations	Gene, Location
Aarskog syndrome	Short stature, hypertelorism, downslanting palpebral fissures, joint hyperextensibility, shawl scrotum	FGD1, Xp11.21
Adrenoleukodystrophy	Variable and progressive vision and hearing loss, spasticity, neurological deterioration associated with demyelination of the central nervous system and adrenal insufficiency	ABCD1, Xq28
Aicardi syndrome	Agenesis of the corpus callosum, lacunar chorioretinopathy, costovertebral anomalies, seizures in females	_____, Xp22
Allan–Herndon syndrome	Generalized muscle hypoplasia, childhood hypotonia, ataxia, athetosis, dysarthria, progressing to spastic paraplegia	MCT8 (SLC16A2), Xq13
ARX-related syndromes (includes Partington, Proud, West, XLAG syndromes and nonsyndromal XLMR)	Partington: dysarthria, dystonia, hyperreflexia, seizures. West: infantile spasms, hypsarrhythmia. Proud: microcephaly, ACC, spasticity, seizures, ataxia, genital anomalies. XLAG: lissencephaly, seizures, genital anomalies	ARX, Xp22.3
ATRX syndrome (includes ARTX, Chudley–Lowry, Carpenter–Waziri, Holmes–Gang, and Martinez spastic paraplegia syndromes and nonsyndromal XLMR)	Short stature, microcephaly, hypotonic facies with hypertelorism, small nose, open mouth and prominent lips, brachydactyly, genital anomalies, hypotonia, in some cases hemoglobin H inclusions in erythrocytes	XNP, (XH2) Xq13.3
Christianson syndrome	Short stature, microcephaly, long narrow face, large ears, long straight nose, prominent mandible, general asthenia, narrow chest, long thin digits, adducted thumbs, contractures, seizures, autistic features, truncal ataxia, ophthalmoplegia, mutism, incontinence, hypoplasia of the cerebellum, and brain stem	SLC9A6, Xq26
Coffin–Lowry syndrome	Short stature, distinctive facies, large soft hands, hypotonia, joint hyperextensibility, skeletal changes	RSK2, Xp22
Creatine transporter deficiency	Nondysmorphic, autistic, possibly progressive	SLC6A8, Xq28
Duchenne muscular dystrophy	Pseudohypertrophic muscular dystrophy	DMD, Xp21.3
Fragile X syndrome	Prominent forehead, long face, recessed midface, large ears, prominent mandible, macroorchidism	FMR1, Xq27.3
Hunter syndrome	Progressive coarsening of face, thick skin, cardiac valve disease, joint stiffening, dysostosis multiplex	IDS, Xq28
Incontinentia pigmenti	Sequence of cutaneous blistering, verrucous thickening, and irregular pigmentation. May have associated CNS, ocular abnormalities	NEMO (IKB6KG), Xq28
Lesch–Nyhan syndrome	Choreoathetosis, spasticity, seizures, self-mutilation, uric acid urinary stones	HPRT, Xq26
Lowe syndrome	Short stature, cataracts, hypotonia, renal tubular dysfunction	OCRL, Xq26.1
MECP2 duplication syndrome	Hypotonia, progressing to spastic paraplegia, recurrent infections	MECP2, Xq28
Menkes syndrome	Growth deficiency, full cheeks, sparse kinky hair, metaphyseal changes, limited spontaneous movement, hypertonicity, seizures, hypothermia, lethargy, arterial tortuosity, death in early childhood	ATP7A, Xpl3.3
Pelizaeus–Merzbacher disease	Nystagmus, truncal hypotonia, progressive spastic paraplegia, ataxia, dystonia	PLP, Xq21.1
Renpenning syndrome (includes Sutherland–Haan, cerebropalatocardiac, Golabi–Ito–Hall, Porteous syndrome	Short stature, microcephaly, small testes. May have ocular or genital abnormalities	PQBP1, Xp11.3
Rett syndrome	XLMR in girls, cessation and regression of development in early childhood, truncal ataxia, autistic features, acquired microcephaly	MECP2, Xq28
X-linked hydrocephaly-MASA spectrum	Hydrocephalus, adducted thumbs, spastic paraplegia	L1CAM, Xq28

Reproduced with permission from Stevenson and Schwartz. ⁴⁶